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Sample records for natural products synthesis

  1. Combinatorial synthesis of natural products

    DEFF Research Database (Denmark)

    Nielsen, John

    2002-01-01

    for preparation of combinatorial libraries. In other examples, natural products or intermediates have served as building blocks or scaffolds in the synthesis of complex natural products, bioactive analogues or designed hybrid molecules. Finally, structural motifs from the biologically active parent molecule have......Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...

  2. Synthesis of Polycyclic Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Tuan Hoang [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents a worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.

  3. Synthesis of Polycyclic Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Tuan Hoang Nguyen

    2003-05-31

    With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents a worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.

  4. Stereoselective Halogenation in Natural Product Synthesis.

    Science.gov (United States)

    Chung, Won-jin; Vanderwal, Christopher D

    2016-03-24

    At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp(3) -hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

  5. Combinatorial synthesis of natural products

    DEFF Research Database (Denmark)

    Nielsen, John

    2002-01-01

    Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...

  6. Natural product synthesis at the interface of chemistry and biology.

    Science.gov (United States)

    Hong, Jiyong

    2014-08-11

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences.

  7. Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products

    Directory of Open Access Journals (Sweden)

    Markus Kaiser

    2013-01-01

    Full Text Available Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclodepsipeptide natural products, thereby illustrating obstacles of cyclodepsipeptide synthesis as well as their overcomings.

  8. Stereoselective Total Synthesis of Bioactive Marine Natural Product Biselyngbyolide B.

    Science.gov (United States)

    Das, Sayantan; Paul, Debobrata; Goswami, Rajib Kumar

    2016-04-15

    A convergent strategy for the stereoselective total synthesis of biologically active marine natural product biselyngbyolide B has been developed. Key strategies of this synthesis include Jamison protocol of trans-hydroalumination/allylation for installation of C18-C23 olefin moiety and intramolecular Heck coupling for macrocyclization.

  9. Green Synthesis of a Fluorescent Natural Product

    Science.gov (United States)

    Young, Douglas M.; Welker, Jacob J. C.; Doxsee, Kenneth M.

    2011-01-01

    Synthesis of 4-methylumbelliferone via the acid-catalyzed Pechmann condensation introduces students to several types of organic reactions: transesterification, electrophilic aromatic substitution, and alcohol dehydration. Performed with a recyclable, solid catalyst and under solvent-free conditions, the experiment illustrates many of the…

  10. Total synthesis and biological activity of natural product Urukthapelstatin A.

    Science.gov (United States)

    Lin, Chun-Chieh; Tantisantisom, Worawan; McAlpine, Shelli R

    2013-07-19

    Herein we report the first total synthesis of the natural product Urkuthaplestatin A (Ustat A) utilizing a convergent synthetic strategy. The characterization and biological activity match those of the previously published natural product. Interestingly, several intermediates, including the linear and serine cyclized precursors, show a 100-fold decrease in cytotoxicity, with IC50's in the low micromolar range. These data indicate that the rigidity and the consecutive aromatic heterocyclic system are responsible for the biological activity.

  11. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

    Science.gov (United States)

    Crane, Erika A; Gademann, Karl

    2016-03-14

    Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

  12. Expedient total synthesis of pyrrothine natural products and analogs

    DEFF Research Database (Denmark)

    Hjelmgaard, Thomas; Givskov, Michael Christian; Nielsen, John

    2007-01-01

    This paper describes an expedient and straightforward total synthesis of the two pyrrothine natural products holomycin (7 steps, 11% overall) and xenorhabdin I (7 steps, 11% overall) and analogs thereof via a common late-stage intermediate. The pathway proceeds via the pyrrothine hydrochloride...

  13. Conceptual process synthesis for recovery of natural products from plants

    DEFF Research Database (Denmark)

    Malwade, Chandrakant R.; Qu, Haiyan; Rong, Ben-Guang;

    2013-01-01

    A systematic method of conceptual process synthesis for recovery of natural products from their biological sources is presented. This methodology divides the task into two major subtasks namely, isolation of target compound from a chemically complex solid matrix of biological source (crude extract......) and purification of target compound(s) from the crude extract. Process analytical technology (PAT) is used in each step to understand the nature of material systems and separation characteristics of each separation method. In the present work, this methodology is applied to generate process flow sheet for recovery...

  14. Redirecting photosynthetic reducing power toward bioactive natural product synthesis.

    Science.gov (United States)

    Nielsen, Agnieszka Zygadlo; Ziersen, Bibi; Jensen, Kenneth; Lassen, Lærke Münter; Olsen, Carl Erik; Møller, Birger Lindberg; Jensen, Poul Erik

    2013-06-21

    In addition to the products of photosynthesis, the chloroplast provides the energy and carbon building blocks required for synthesis of a wealth of bioactive natural products of which many have potential uses as pharmaceuticals. In the course of plant evolution, energy generation and biosynthetic capacities have been compartmentalized. Chloroplast photosynthesis provides ATP and NADPH as well as carbon sources for primary metabolism. Cytochrome P450 monooxygenases (P450s) in the endoplasmic reticulum (ER) synthesize a wide spectrum of bioactive natural products, powered by single electron transfers from NADPH. P450s are present in low amounts, and the reactions proceed relatively slowly due to limiting concentrations of NADPH. Here we demonstrate that it is possible to break the evolutionary compartmentalization of energy generation and P450-catalyzed biosynthesis, by relocating an entire P450-dependent pathway to the chloroplast and driving the pathway by direct use of the reducing power generated by photosystem I in a light-dependent manner. The study demonstrates the potential of transferring pathways for structurally complex high-value natural products to the chloroplast and directly tapping into the reducing power generated by photosynthesis to drive the P450s using water as the primary electron donor.

  15. An Improved Synthesis of the Natural Product Isorhapontigenin

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    We have developed an alternative route to synthesize the natural product, isorhapotogenin . The synthetic product was characterized by IR and 1H-NMR in comparison with the corresponding natural product.

  16. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    Science.gov (United States)

    Maertens, Gaetan; L'homme, Chloe; Canesi, Sylvain

    2014-12-01

    We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the “aromatic ring umpolung” concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor), acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor), erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis). These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

  17. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    Directory of Open Access Journals (Sweden)

    Gaetan eMaertens

    2015-01-01

    Full Text Available We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the aromatic ring umpolung concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol, a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor, acetylaspidoalbidine (an antitumor agent, fortucine (antiviral and antitumor, erysotramidine (curare-like effect, platensimycin (an antibiotic, and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis. These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

  18. "Common synthetic scaffolds" in the synthesis of structurally diverse natural products.

    Science.gov (United States)

    Anagnostaki, Elissavet E; Zografos, Alexandros L

    2012-09-01

    Selected natural products have long been considered as desirable targets for total synthesis due to their unique biological properties and their challenging structural complexity. Laboratory synthesis of natural compounds usually relies on target-oriented synthesis, involving the production, isolation and purification of successive intermediates, requiring multiple steps to arrive to the final product. A far more economical approach using common synthetic scaffolds that can be readily transformed through biomimetic-like pathways to a range of structurally diverse natural products has been evolved in the last decade, leading synthesis to new directions. This tutorial review critically presents the hallmarks in this field.

  19. First total synthesis of a natural product containing a chiral, beta-diketone: synthesis and stereochemical reassignment of siphonarienedione and siphonarienolone.

    Science.gov (United States)

    Calter, Michael A; Liao, Wensheng

    2002-11-06

    The first total syntheses of siphonarienolone and siphonarienedione are described. The development of a stereoselective synthesis of beta-diketones facilitated the synthesis of the latter compound. The synthesis of the structures proposed for the natural products afforded compounds whose spectral data did not match those of the natural products. However, the synthesis of compounds isomeric to the proposed structures at C(4) and C(5) afforded compounds identical to the natural products, thereby reassigning the stereochemistry of the natural products.

  20. Studies on the Synthesis of a Natural Product-Piceatannol and its Analogs

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Piceatannol, (E)-3, 3(, 4, 5(-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.

  1. Synthesis and biological properties of macrolactam analogs of the natural product macrolide (-)-A26771B.

    Science.gov (United States)

    Canova, Sophie; Lépine, Renaud; Thys, Amber; Baron, Anne; Roche, Didier

    2011-08-15

    Promising synthetic derivatives of macrolactone natural product (-)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (-)-A26771B with improved antibacterial activity and metabolic stability.

  2. Phenazines and natural products; Novel synthesis of saphenic acid

    DEFF Research Database (Denmark)

    Petersen, Lars; Jensen, Knud Jørgen; Nielsen, John

    1999-01-01

    The natural product saphenic acid (6-(1-hydroxyethyl)1-phenazinecarboxylic acid) was synthesized from readily accessible starting materials. The desired product was obtained in an overall yield of 22% for four steps with the key steps being formation of a diphenylamine, followed by cyclization un...... under alkaline and reducing conditions. Assignments of H-1 NMR spectra were achieved by homo- and heteronuclear 1D and 2D correlations. Double pulsed field gradient spin-echo one-dimensional NOESY proved especially valuable for assignment of aromatic protons....

  3. Phenazines and natural products; novel synthesis of saphenic acid

    DEFF Research Database (Denmark)

    Petersen, Lars; Jensen, Knud J.; Nielsen, John

    1999-01-01

    The natural product saphenic acid (6-(1-hydroxyethyl)1- phenazinecarboxylic acid) was synthesized from readily accessible starting materials. The desired product was obtained in an overall yield of 22% for four steps with the key steps being formation of a diphenylamine, followed by cyclization u...... under alkaline and reducing conditions. Assignments of 1H NMR spectra were achieved by homo- and heteronuclear 1D and 2D correlations. Double pulsed field gradient spin-echo one-dimensional NOESY proved especially valuable for assignment of aromatic protons....

  4. Stereospecific Synthesis of the Geometrical Isomers of a Natural Product

    Science.gov (United States)

    Grove, T.; DiLella, D.; Volker, E.

    2006-01-01

    Stereospecific synthesis of a geometrical isomer is not a common topic for the introductory organic chemistry laboratory. We have developed and tested an experiment for the synthesis of (Z) and (E) isomers that has been performed successfully by undergraduate students. The experiment is presented to the students as a puzzle in which they must…

  5. Synthesis of four diastereomers of sclerophytin F and structural reassignment of several sclerophytin natural products.

    Science.gov (United States)

    Clark, J Stephen; Delion, Laëtitia; Farrugia, Louis J

    2015-03-16

    Synthesis of the triol that has been proposed to be the marine natural product sclerophytin F has been completed along with the syntheses of three diastereomers. Comparison of the NMR spectroscopic data for all four compounds to the data reported for the natural product reveals that sclerophytin F is not the 3S diastereomer of sclerophytin A as proposed by Friedrich and Paquette. Re-analysis of the NMR spectroscopic data for known sclerophytin natural products and synthetic analogues leads to the conclusion that sclerophytins E and F are the same compound. This finding has allowed structural reassignment of several other cladiellin natural products.

  6. Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

    Directory of Open Access Journals (Sweden)

    Jeyun Jo

    2017-06-01

    Full Text Available Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner.

  7. Natural Product Total Synthesis in the Organic Laboratory: Total Synthesis of Caffeic Acid Phenethyl Ester (CAPE), a Potent 5-Lipoxygenase Inhibitor from Honeybee Hives

    Science.gov (United States)

    Touaibia, Mohamed; Guay, Michel

    2011-01-01

    Natural products play a critical role in modern organic synthesis and learning synthetic techniques is an important component of the organic laboratory experience. In addition to traditional one-step organic synthesis laboratories, a multistep natural product synthesis is an interesting experiment to challenge students. The proposed three-step…

  8. Natural Product Total Synthesis in the Organic Laboratory: Total Synthesis of Caffeic Acid Phenethyl Ester (CAPE), a Potent 5-Lipoxygenase Inhibitor from Honeybee Hives

    Science.gov (United States)

    Touaibia, Mohamed; Guay, Michel

    2011-01-01

    Natural products play a critical role in modern organic synthesis and learning synthetic techniques is an important component of the organic laboratory experience. In addition to traditional one-step organic synthesis laboratories, a multistep natural product synthesis is an interesting experiment to challenge students. The proposed three-step…

  9. Survey of marine natural product structure revisions: a synergy of spectroscopy and chemical synthesis.

    Science.gov (United States)

    Suyama, Takashi L; Gerwick, William H; McPhail, Kerry L

    2011-11-15

    The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products that were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially when considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable 'detective work' remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques.

  10. De novo synthesis of natural products via the asymmetric hydration of polyenes.

    Science.gov (United States)

    Wang, Yanping; Xing, Yalan; Zhang, Qi; O'Doherty, George A

    2011-08-14

    For the last ten years our group has been working toward the development of an asymmetric hydration approach to polyketide natural products based on the regioselective hydration of di- and tri-enoates. Key to the success of this approach is the recognition that both high regiocontrol and asymmetric induction could be obtained by the use of a Sharpless asymmetric dihydroxylation reaction. Herein we describe the development of the method and its application to natural product total synthesis.

  11. Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products.

    Science.gov (United States)

    Annamalai, Murali; Hristeva, Stanimira; Bielska, Martyna; Ortega, Raquel; Kumar, Kamal

    2017-05-18

    Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp³ character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp³ features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium.

  12. Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives: Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural Product

    Science.gov (United States)

    Fuwa, Haruhiko

    2016-01-01

    Tetrahydropyrans are structural motifs that are abundantly present in a range of biologically important marine natural products. As such, significant efforts have been paid to the development of efficient and versatile methods for the synthesis of tetrahydropyran derivatives. Neopeltolide, a potent antiproliferative marine natural product, has been an attractive target compound for synthetic chemists because of its complex structure comprised of a 14-membered macrolactone embedded with a tetrahydropyran ring, and twenty total and formal syntheses of this natural product have been reported so far. This review summarizes the total and formal syntheses of neopeltolide and its analogues, highlighting the synthetic strategies exploited for constructing the tetrahydropyran ring. PMID:27023567

  13. Recent Advances in the Total Synthesis of Tetramic Acid-Containing Natural Products

    Directory of Open Access Journals (Sweden)

    Wen-Ju Bai

    2016-01-01

    Full Text Available With incredible bioactivities and fascinating structural complexities, tetramic acid- (TA- containing natural products have attracted favorable attention among the organic chemistry community. Although the construction of the TA core is usually straightforward, the intricate C3-side chain sometimes asks for some deliberative strategy so as to fulfill an elegant total synthesis. This review mainly covers some exceptional synthetic examples for each type of natural product in recent years, showcasing the great achievements as well as unsettled obstacles in this area, in the hope of accelerating the synthetic and biological investigations for this unique type of natural product.

  14. Lepadiformine: a case study of the value of total synthesis in natural product structure elucidation.

    Science.gov (United States)

    Weinreb, Steven M

    2003-01-01

    Since the emergence of routine X-ray crystallography and high-field FT NMR in the mid-twentieth century, the importance of total synthesis in structure elucidation has become underappreciated by most organic chemists. However, the limitations and fallibility of spectral methodology has recently been highlighted by the mischaracterization of a number of complex natural products, the correct structures of which were all ultimately assigned by total synthesis. This account describes how total synthesis was not only instrumental in disproving the erroneously assigned structure of the marine alkaloid, lepadiformine, but also was also pivotal in establishing the correct structure and absolute configuration.

  15. Stereospecific Synthesis of the Skeleton of the Antitumor Marine Natural Product Et-743

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-Zhu; TANG Ye-Feng; WANG Ye; CHEN Shi-Zhi

    2003-01-01

    @@ Ecteinascidin 743 (Et-743) is an exceedingly potent antitumor agent isolated from the marine tunicate Ecteinascidia turbinate. As its structurally simplified version, Phthalascidin was found to retain the cytotoxicity of the natural product. Their novel structures, impressive biological activities and difficult availabilities conspire to render the attractive targets for total synthesis.

  16. Recent applications of intramolecular Diels-Alder reactions to natural product synthesis

    DEFF Research Database (Denmark)

    Juhl, M.; Tanner, David Ackland

    2009-01-01

    This tutorial review presents some recent examples of intramolecular Diels-Alder (IMDA) reactions as key complexity-generating steps in the total synthesis of structurally intricate natural products. The opportunities afforded by transannular (TADA) versions of the IMDA reaction in complex molecu...

  17. Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today's medicine.

    Science.gov (United States)

    Ghosh, Arun K

    2010-12-03

    In this Perspective, I outline my group's research involving the chemical syntheses of medicinally important natural products, exploration of their bioactivity, and the development of new asymmetric carbon-carbon bond-forming reactions. This paper also highlights our approach to molecular design and synthesis of conceptually novel inhibitors against target proteins involved in the pathogenesis of human diseases, including AIDS and Alzheimer's disease.

  18. Silver-catalyzed one-pot synthesis of arylnaphthalene lactone natural products.

    Science.gov (United States)

    Foley, Patrick; Eghbali, Nicolas; Anastas, Paul T

    2010-05-28

    Naturally occurring arylnaphthalene lactone lignans have demonstrated a variety of valuable medicinal chemistry properties and have therefore been of continued interest to drug discovery research. Our group has demonstrated a silver-catalyzed one-pot synthesis of the arylnaphthalene lactone core using carbon dioxide, phenylpropargyl chloride, and phenylacetylene. This new approach has been employed in the synthesis of six arylnaphthalene lactone natural products: retrochinensin (1), justicidin B (2), retrojusticidin B (3), chinensin (4), justicidin E (5), and taiwanin C (6). Additionally, an arylnaphthalene lactone regioisomer was isolated (9), which we refer to as isoretrojusticidin B.

  19. Chemical biology--identification of small molecule modulators of cellular activity by natural product inspired synthesis.

    Science.gov (United States)

    Hübel, Katja; Lessmann, Torben; Waldmann, Herbert

    2008-07-01

    The aim of this tutorial review is to introduce the reader to the concept, synthesis and application of natural product-inspired compound collections as an important field in chemical biology. This review will discuss how potentially interesting scaffolds can be identified (structural classification of natural products), synthesized in an appropriate manner (including stereoselective transformations for solid phase-bound compounds) and tested in biological assays (cell-based screening as well as biochemical in vitro assays). These approaches will provide the opportunity to identify new and interesting compounds as well as new targets for chemical biology and medicinal chemistry research.

  20. Synthesis of Complex Natural Products as a Vehicle for Student-Centered, Problem-Based Learning

    Science.gov (United States)

    Cannon, Kevin J.; Krow, Grant R.

    1998-10-01

    Management strategies for upper-level undergraduate and graduate courses in organic synthesis at Temple University are described, and both student and faculty responsibilities are discussed. Using natural product synthesis as a vehicle, students choose a synthetic problem from the literature, identify the knowledge needed to solve the problem, explore resources for attaining that knowledge, identify the goals and criteria for a successful synthetic plan, and create and do assessments of their work. The method is an example of teacher-guided, student-directed, interdependent, small-group, problem-based learning.

  1. SmI(2)-induced reductive cyclizations for the synthesis of cyclic ethers and applications in natural product synthesis.

    Science.gov (United States)

    Nakata, Tadashi

    2010-06-01

    This tutorial review covers SmI(2)-induced reductive cyclizations of beta-alkoxyacrylate, beta-alkoxyvinyl sulfone, and beta-alkoxyvinyl sulfoxide, as methods for efficient construction of cyclic ethers. These cyclizations were developed as tools to aid in the total synthesis of marine polycyclic ethers, whose complex, synthetically challenging structures and potent bioactivities have attracted the attention of numerous synthetic organic chemists. Applications of the methods to total syntheses of various natural products containing cyclic ether are also described.

  2. Enantioselective synthesis of the predominant AB ring system of the Schisandra nortriterpenoid natural products.

    Science.gov (United States)

    Gockel, Birgit; Goh, Shermin S; Puttock, Emma J; Baars, Hannah; Chaubet, Guilhem; Anderson, Edward A

    2014-09-01

    An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a β-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.

  3. The flow synthesis of heterocycles for natural product and medicinal chemistry applications.

    Science.gov (United States)

    Baumann, Marcus; Baxendale, Ian R; Ley, Steven V

    2011-08-01

    This article represents an overview of recent research from the Innovative Technology Centre in the field of flow chemistry which was presented at the FROST2 meeting in Budapest in October 2009. After a short introduction of this rapidly expanding field, we discuss some of our results with a main focus on the synthesis of heterocyclic compounds which we use in various natural product and medicinal chemistry programmes.

  4. Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

    Directory of Open Access Journals (Sweden)

    Jens Schmidt

    2014-05-01

    Full Text Available The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423 in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.

  5. Synthesis of furanone-based natural product analogues with quorum sensing antagonist activity

    DEFF Research Database (Denmark)

    Hjelmgaard, Thomas; Persson, T.; Rasmussen, Thomas Bovbjerg;

    2003-01-01

    The synthesis of 5- and 3-(1'-hydroxyalkyl)-substituted 5H-furan-2-ones 4a-d and 8a-d as well as 5-alkylidene-5H-furan-2-ones 5a-d is described. A study of the structure-activity relationship of these furanone-based natural product analogues towards two different quorum sensing systems is reported....... Although the synthesized compounds are not as potent quorum sensing inhibitors as some natural counterparts and a synthetic analogue hereof, interesting structure-activity relationships are seen....

  6. The direct oxidative diene cyclization and related reactions in natural product synthesis

    Directory of Open Access Journals (Sweden)

    Juliane Adrian

    2016-09-01

    Full Text Available The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (diastereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.

  7. Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

    Science.gov (United States)

    Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

    2014-07-01

    Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

  8. Total synthesis approaches to natural product derivatives based on the combination of chemical synthesis and metabolic engineering.

    Science.gov (United States)

    Kirschning, Andreas; Taft, Florian; Knobloch, Tobias

    2007-10-21

    Secondary metabolites are an extremely diverse and important group of natural products with industrial and biomedical implications. Advances in metabolic engineering of both native and heterologous secondary metabolite producing organisms have allowed the directed synthesis of desired novel products by exploiting their biosynthetic potentials. Metabolic engineering utilises knowledge of cellular metabolism to alter biosynthetic pathways. An important technique that combines chemical synthesis with metabolic engineering is mutasynthesis (mutational biosynthesis; MBS), which advanced from precursor-directed biosynthesis (PDB). Both techniques are based on the cellular uptake of modified biosynthetic intermediates and their incorporation into complex secondary metabolites. Mutasynthesis utilises genetically engineered organisms in conjunction with feeding of chemically modified intermediates. From a synthetic chemist's point of view the concept of mutasynthesis is highly attractive, as the method combines chemical expertise with Nature's synthetic machinery and thus can be exploited to rapidly create small libraries of secondary metabolites. However, in each case, the method has to be critically compared with semi- and total synthesis in terms of practicability and efficiency. Recent developments in metabolic engineering promise to further broaden the scope of outsourcing chemically demanding steps to biological systems.

  9. Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis.

    Science.gov (United States)

    Paek, Seung-Mann; Jeong, Myeonggyo; Jo, Jeyun; Heo, Yu Mi; Han, Young Taek; Yun, Hwayoung

    2016-07-21

    Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas.

  10. Synthesis of a Natural Product-Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides

    DEFF Research Database (Denmark)

    Petersen, Rico; Le Quement, Sebastian Thordal; Nielsen, Thomas Eiland

    2014-01-01

    Massive efforts in molecular library synthesis have strived for the development of synthesis methodology which systematically delivers natural product-like compounds of high spatial complexity. Herein, we present a conceptually simple approach that builds on the power of solid-phase peptide......- ically diverse compounds was generated, and selected com- pounds were elaborated into isoform-selective metalloprotease inhibitors...

  11. Synthesis of a Natural Product-Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides

    DEFF Research Database (Denmark)

    Petersen, Rico; Le Quement, Sebastian Thordal; Nielsen, Thomas Eiland

    2014-01-01

    Massive efforts in molecular library synthesis have strived for the development of synthesis methodology which systematically delivers natural product-like compounds of high spatial complexity. Herein, we present a conceptually simple approach that builds on the power of solid-phase peptide......- ically diverse compounds was generated, and selected com- pounds were elaborated into isoform-selective metalloprotease inhibitors....

  12. Process synthesis for natural products from plants based on PAT methodology

    DEFF Research Database (Denmark)

    2017-01-01

    generates different process flowsheet alternatives consisting of multiple separation techniques. Decision making is supported by heuristics as well as basic process information already available from previous studies. In addition, process analytical technology (PAT) framework, a part of Quality by Design...... (QbD) approach, has been included at various steps to obtain molecular level information of process streams and thereby, support the rational decision making. The formulated methodology has been used to isolate and purify artemisinin, an antimalarial drug, from dried leaves of the plant Artemisia...... and other consumer products. Therefore, process technology towards industrial scale production of such high value chemicals from plants has significant importance. In this chapter, a process synthesis methodology for recovery of natural products from plants at conceptual level is discussed. The methodology...

  13. Crotylsilane reagents in the synthesis of complex polyketide natural products: total synthesis of (+)-discodermolide.

    Science.gov (United States)

    Arefolov, Alexander; Panek, James S

    2005-04-20

    An efficient, highly convergent stereocontrolled synthesis of (+)-discodermolide has been achieved with 2.1% overall yield (27 steps longest linear sequence). The absolute stereochemistry of the C1-C6 (12), C7-C14 (13), and C15-C24 (11) subunits was introduced using asymmetric crotylation methodology. Key elements of the synthesis include the use of hydrozirconation-cross-coupling methodology for the construction of C13-C14 (Z)-olefin, acetate aldol reaction to construct the C6-C7 bond and install the C7 stereocenter with high levels of 1,5-anti stereoinduction, and the use of palladium-mediated sp(2)-sp(3) cross-coupling reaction to join the advanced fragments, which assembled the carbon framework of discodermolide.

  14. Total Synthesis of the Natural Product-Pinosylvin and its Analog

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    We synthesised a natural product (10) , isolated from G.parvifolium , and its analog. The synthetic product was characterized by elemental analysis and 1H-NMR in comparision with the corresponding natural product.

  15. Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products.

    Science.gov (United States)

    Ghislieri, Diego; Green, Anthony P; Pontini, Marta; Willies, Simon C; Rowles, Ian; Frank, Annika; Grogan, Gideon; Turner, Nicholas J

    2013-07-24

    The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.

  16. Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives.

    Science.gov (United States)

    Li, Jun; Li, Jianzu; Xu, Yuan; Wang, Yunjie; Zhang, Luyong; Ding, Li; Xuan, Yining; Pang, Tao; Lin, Hansen

    2016-01-01

    The natural product (+)-balasubramide (3j) and its derivatives (3a-3i) were synthesized using a two-step asymmetric synthesis, and the biological activities of 3a-3j were determined in vitro. Methyl (2S,3R)-(+)-3-phenyloxirane-2-carboxylate (1h), the asymmetric synthesis of which was described in a previous paper, was selected as the starting material. Compounds 3a-3j were evaluated for their neuroprotective, antioxidative, and anti-neuroinflammatory effects. (+)-Balasubramide and its derivatives with different electronegative groups in the 6-phenyl ring produced little neuroprotection and antioxidation, but induced potent anti-neuroinflammatory effects in BV-2 microglial cells (with the exception of 3g). Compound 3c, with a trifluoromethyl group in its 6-phenyl ring, was a particularly potent anti-neuroinflammatory agent. These results demonstrated that the electronegativity of the 6-phenyl ring of (+)-balasubramide is an important determinant of its inhibitory effect on neuroinflammation. More electronegative substituents result in more potent anti-neuroinflammatory effects. Moreover, cytotoxicity assays indicated no significant effects of the tested compounds.

  17. [Development of novel synthetic organic reactions: synthesis of antitumor natural products and leading compounds for new pharmaceuticals].

    Science.gov (United States)

    Kita, Yasuyuki

    2002-12-01

    Biologically active natural products with unique, highly complex molecular skeletons have been used as leading compounds for raw materials of new drugs. Due to the limitations of natural supply, highly efficient, large-scale syntheses and molecular design have been sought in drug discovery. For this purpose, we have focused on a synthetic strategy effective in developing novel reactions and reagents and found several useful regio- and stereospecific reactions, contributing to the synthesis of otherwise unattainable target molecules. The application of these reactions for the total synthesis of three types of potent cytotoxic natural products for the first time is described in this paper. The basic concept is first described. Then the total synthesis of anthracyclines, fredericamycin A, and discorhabdins is reported. Novel reactions using hypervalent iodine reagents under environmentally benign conditions are also described. The future prospects for this method are discussed.

  18. Total Synthesis of Vinblastine, Vincristine, Related Natural Products, and Key Structural Analogues

    Science.gov (United States)

    Ishikawa, Hayato; Colby, David A.; Seto, Shigeki; Va, Porino; Tam, Annie; Kakei, Hiroyuki; Rayl, Thomas J.; Hwang, Inkyu; Boger, Dale L.

    2009-01-01

    Full details of the development of a direct coupling of catharanthine with vindoline to provide vinblastine are described along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)–NaBH4/air solution leads to oxidation of the C15′–C20′ double bond and reduction of the intermediate iminium ion directly providing vinblastine (40–43%) and leurosidine (20–23%), its naturally occurring C20′ alcohol isomer. The yield of coupled products, which exclusively possess the natural C16′ stereochemistry, approaches or exceeds 80% and the combined yield of the isomeric C20′ alcohols is >60%. Preliminary studies of Fe(III)–NaBH4/air oxidation reaction illustrate a generalizable trisubstituted olefin scope, identified alternatives to O2 trap at the oxidized carbon, provides a unique entry into C20′ functionalized vinblastines, and affords initial insights into the observed C20′ diastereoselectivity. The first disclosure of the use of exo-catharanthine proceeding through Δ19′,20′-anhydrovinblastine in such coupling reactions is also detailed with identical stereochemical consequences. Incorporating either a catharanthine N-methyl group or a vindoline N-formyl group precludes Fe(III)-promoted coupling, whereas the removal of the potentially key C16 methoxy group of vindoline does not adversely impact the coupling efficiency. Extension of these studies provided a total synthesis of vincristine (2) via N-desmethylvinblastine (36, also a natural product), 16-desmethoxyvinblastine (44) and 4-desacetoxy-16-desmethoxyvinblastine (47) both of which we can now suggest are likely natural products produced by C. roseus, desacetylvinblastine (62) and 4-desacetoxyvinblastine (59), as well as a series of key

  19. Synthesis gas production via hybrid steam reforming of natural gas and bio-liquids

    NARCIS (Netherlands)

    Balegedde Ramachandran, P.

    2013-01-01

    This thesis deals with (catalytic) steam reforming of bio-liquids for the production of synthesis gas. Glycerol, both crude from the biodiesel manufacturing and refined, and pyrolysis oil are tested as bio-based feedstocks. Liquid bio-based feeds could be preferred over inhomogeneous fibrous solid b

  20. Synthesis, characterization and wound healing imitation of Fe3O4 magnetic nanoparticle grafted by natural products

    Science.gov (United States)

    Pala, Sravan Kumar

    This research focused on the study of the core-shelled magnetic nanomaterials derived from a colloidal chemistry. The goals are four-fold: (1) synthesis of Fe3O4MNMs using colloidal chemistry. The Fe 3O4 MNMs were then grafted with extracts derived from natural products, namely Olecraceavar italica (broccoli), Boletus edulis (mushroom)and Solanum lycopersicum (tomato);(2)characterization of natural products by chromatography and mass spectrometry;(3) characterization of MNMs to determine their crystallinity, morphological and elemental composition by the state-of-the-art instruments; and (4) biological evaluation using Gram-negative and Gram-positive bacteria. The approach provides advantages to precisely control the composition and homogeneity. The second advantage of the colloidal chemistry is its user friendliness and feasibility. Due to the nature of the natural products, the compatibility of MNM is anticipated to be enhanced.In this chapter, the nanomaterials will be discussed from four perspectives,§1.1 Nanotechnology (§1.1), §1.2 Synthesis of nanomaterials; §1.3 The natural product extract,; §1.4 Characterization of nanomaterials; and §1.5Biological application of nanomaterials.Fig. 1 summarized the overarching goals of this study.

  1. Synthesis of psymberin analogues: probing a functional correlation with the pederin/mycalamide family of natural products.

    Science.gov (United States)

    Jiang, Xin; Williams, Noelle; De Brabander, Jef K

    2007-01-18

    In this letter we describe an efficient synthesis of "psympederin", a hybrid between the novel antitumor natural product psymberin and the blister beetle toxin pederin. Evaluation of antiproliferative activity reveals that the dihydroisocoumarin fragment is important for psymberin toxicity and the cyclic pederate fragment is important for pederin/mycalamide toxicity. On the basis of preliminary results described herein, we speculate that, despite their structural resemblance, psymberin and pederin/mycalamide induce toxicity through different mechanisms. [reaction: see text].

  2. A Novel Synthesis of 1-Acetyl-4-Isopropenyl-1-Cyclopentene by Chemoselective Cyclization of 4-Methyl-3-(Oxobutyl-4-Pentenal: An Important Intermediate for Natural Product Synthesis

    Directory of Open Access Journals (Sweden)

    Castro Fernando de Lima

    1999-01-01

    Full Text Available This article presents the direct oxidation of limonene-oxide 1 with KIO4 in water, which is the best way to obtain the keto-aldehyde 3, an important intermediate in natural product synthesis. The cyclization of keto-aldehyde 3 with acidic Al2O3 proceeds chemoselectively to give ketone 4. These two reactions together increase the overall yield of ketone 4 to about 70% compared to 8% previously reported in the literature¹.

  3. Solid-Phase Iminium Cyclization Reactions for the Synthesis of Natural Product-Like Diketopiperazines

    DEFF Research Database (Denmark)

    Petersen, Rico

    The development of methodology for the solid-phase synthesis of fused 2,5-diketopiperazines with an emphasis on structural and stereochemical control, has been accomplished through two different approaches. The first approach was based on a highly trans-stereoselective (82% d.e.) intramolecular N......]tetrahydroisoquinoline product in a high purity (71%). Unfortunately an issue with incomplete conversion in the final step (20%) rendered separation of the diastereoisomers, by preparative RP-HPLC, problematic. Employing the developed methods, a diastereoisomeric matrix of aminomethylthiophene hydroxamic acid biased HDAC...

  4. Isolation of Betulin and Rearrangement to Allobetulin: A Biomimetic Natural Product Synthesis

    Science.gov (United States)

    Green, Brian; Bentley, Michael D.; Chung, Bong Y.; Lynch, Nicholas G.; Jensen, Bruce L.

    2007-01-01

    The triterpenes are a diverse class of widely distributed natural products derived from squalene. Various cyclization and subsequent rearrangement reactions produce many complex structural types. These compounds frequently display a wide divergence of biological properties. For example the pentacyclic triterpene, betulin, is isolated from white…

  5. Isolation of Betulin and Rearrangement to Allobetulin: A Biomimetic Natural Product Synthesis

    Science.gov (United States)

    Green, Brian; Bentley, Michael D.; Chung, Bong Y.; Lynch, Nicholas G.; Jensen, Bruce L.

    2007-01-01

    The triterpenes are a diverse class of widely distributed natural products derived from squalene. Various cyclization and subsequent rearrangement reactions produce many complex structural types. These compounds frequently display a wide divergence of biological properties. For example the pentacyclic triterpene, betulin, is isolated from white…

  6. Natural product derived antiprotozoal agents: synthesis, biological evaluation, and structure-activity relationships of novel chromene and chromane derivatives.

    Science.gov (United States)

    Harel, Dipak; Schepmann, Dirk; Prinz, Helge; Brun, Reto; Schmidt, Thomas J; Wünsch, Bernhard

    2013-09-26

    Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani.

  7. Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

    Science.gov (United States)

    Atkinson, Darcy J; Naysmith, Briar J; Furkert, Daniel P

    2016-01-01

    Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an uncultured bacterial source, and demonstrates remarkably high potency against a wide range of resistant pathogens without apparent development of resistance. A rare amino acid residue component of teixobactin, enduracididine, is only known to occur in a small number of natural products that also possess promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges encountered to date in the development of efficient synthetic routes to facilitate drug discovery efforts inspired by the discovery of teixobactin. PMID:28144300

  8. Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

    Directory of Open Access Journals (Sweden)

    Darcy J. Atkinson

    2016-11-01

    Full Text Available Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an uncultured bacterial source, and demonstrates remarkably high potency against a wide range of resistant pathogens without apparent development of resistance. A rare amino acid residue component of teixobactin, enduracididine, is only known to occur in a small number of natural products that also possess promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges encountered to date in the development of efficient synthetic routes to facilitate drug discovery efforts inspired by the discovery of teixobactin.

  9. Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis

    Science.gov (United States)

    Sattely, Elizabeth S.; Meek, Simon J.; Malcolmson, Steven J.; Schrock, Richard R.; Hoveyda, Amir H.

    2010-01-01

    A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee). PMID:19113867

  10. Identification of a Pantoea biosynthetic cluster that directs the synthesis of an antimicrobial natural product.

    Directory of Open Access Journals (Sweden)

    Alyssa M Walterson

    Full Text Available Fire Blight is a destructive disease of apple and pear caused by the enteric bacterial pathogen, Erwinia amylovora. E. amylovora initiates infection by colonizing the stigmata of apple and pear trees, and entering the plants through natural openings. Epiphytic populations of the related enteric bacterium, Pantoea, reduce the incidence of disease through competition and antibiotic production. In this study, we identify an antibiotic from Pantoea ananatis BRT175, which is effective against E. amylovora and select species of Pantoea. We used transposon mutagenesis to create a mutant library, screened approximately 5,000 mutants for loss of antibiotic production, and recovered 29 mutants. Sequencing of the transposon insertion sites of these mutants revealed multiple independent disruptions of an 8.2 kb cluster consisting of seven genes, which appear to be coregulated. An analysis of the distribution of this cluster revealed that it was not present in any other of our 115 Pantoea isolates, or in any of the fully sequenced Pantoea genomes, and is most closely related to antibiotic biosynthetic clusters found in three different species of Pseudomonas. This identification of this biosynthetic cluster highlights the diversity of natural products produced by Pantoea.

  11. Identification of a Pantoea biosynthetic cluster that directs the synthesis of an antimicrobial natural product.

    Science.gov (United States)

    Walterson, Alyssa M; Smith, Derek D N; Stavrinides, John

    2014-01-01

    Fire Blight is a destructive disease of apple and pear caused by the enteric bacterial pathogen, Erwinia amylovora. E. amylovora initiates infection by colonizing the stigmata of apple and pear trees, and entering the plants through natural openings. Epiphytic populations of the related enteric bacterium, Pantoea, reduce the incidence of disease through competition and antibiotic production. In this study, we identify an antibiotic from Pantoea ananatis BRT175, which is effective against E. amylovora and select species of Pantoea. We used transposon mutagenesis to create a mutant library, screened approximately 5,000 mutants for loss of antibiotic production, and recovered 29 mutants. Sequencing of the transposon insertion sites of these mutants revealed multiple independent disruptions of an 8.2 kb cluster consisting of seven genes, which appear to be coregulated. An analysis of the distribution of this cluster revealed that it was not present in any other of our 115 Pantoea isolates, or in any of the fully sequenced Pantoea genomes, and is most closely related to antibiotic biosynthetic clusters found in three different species of Pseudomonas. This identification of this biosynthetic cluster highlights the diversity of natural products produced by Pantoea.

  12. Total Synthesis of a Highly Potent Anticancer Natural Product OSW-1

    Institute of Scientific and Technical Information of China (English)

    Zhendong; Jin

    2001-01-01

    OSW-1 (1) and its four natural analogs (2-5) are five highly potent anticancer natural products that were recently isolated from the bulbs of Ornithogalum saundersiae, a perennial grown in southern Africa (Figure 1).1 The IC50 values of these compounds against human promyelocytic leukemia HL-60 cells range from between 0.1 to 0.3 nM.2 Their anticancer activities are from 10 to 100 times more potent than other well-known anticancer agents in clinical use, including mitomycin C, adriamycin, cisplatin, camptothecin, and taxol. OSW-1 (1), the main constituent of Ornithogalum saundersiae bulbs, is highly cytostatic in the NCI 60-cell in vitro screen, with a mean IC50 of 0.78 nM. It also looks promising from in vivo tests against mouse P388 leukemia (increased life span 59%) by a one-time administration of 0.01 mg/kg.  ……

  13. Total Synthesis of a Highly Potent Anticancer Natural Product OSW-1

    Institute of Scientific and Technical Information of China (English)

    Zhendong Jin; Wensheng Yu

    2001-01-01

    @@ OSW-1 (1) and its four natural analogs (2-5) are five highly potent anticancer natural products that were recently isolated from the bulbs of Ornithogalum saundersiae, a perennial grown in southern Africa (Figure 1).1 The IC50 values of these compounds against human promyelocytic leukemia HL-60 cells range from between 0.1 to 0.3 nM.2 Their anticancer activities are from 10 to 100 times more potent than other well-known anticancer agents in clinical use, including mitomycin C, adriamycin, cisplatin, camptothecin, and taxol. OSW-1 (1), the main constituent of Ornithogalum saundersiae bulbs, is highly cytostatic in the NCI 60-cell in vitro screen, with a mean IC50 of 0.78 nM. It also looks promising from in vivo tests against mouse P388 leukemia (increased life span 59%) by a one-time administration of 0.01 mg/kg.

  14. Synthesis and antioxidant properties of diphenylmethane derivative bromophenols including a natural product.

    Science.gov (United States)

    Balaydin, Halis Türker; Gülçin, Ílhami; Menzek, Abdullah; Göksu, Süleyman; Şahin, Ertan

    2010-10-01

    Bromination of bis(3,4-dimethoxyphenyl)methanone (5) gave four products (6-9) with mono, di, tri, and tetra Br under different conditions. Reduction and demethylation reactions of product 9 with tetra Br were performed, consecutively and a natural product, 5,5'-methylene bis(3,4-dibrombenzene-1,2-diol) (1), was obtained with a 53% yield. Five derivatives, (13-17) (bromophenols), of 1 were also synthesised. The antioxidant and radical scavenging activities of bromophenols 1 and 13-17 were determined by employing various in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH(*)), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS(*+)), N,N-dimethyl-p-phenylenediamine dihydrochloride radical cation (DMPD(*+)), and superoxide anion radical (O(2)(*-)) scavenging, reducing ability determination by the Fe(3+)-Fe(2+) and Cu(2+)-Cu(+) cupric reducing antioxidant capacity (CUPRAC) transformation methods, hydrogen peroxide scavenging, and ferrous ion (Fe(2+)) chelating activities. Moreover, these activities were compared to those of synthetic standard antioxidant compounds such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol, and trolox. The results showed that the synthesised bromophenols had effective antioxidant power.

  15. Natural products for plant protection

    Directory of Open Access Journals (Sweden)

    Čeković Živorad

    2006-01-01

    Full Text Available The advantage applying natural products, such as a secondary metabolites, in plant protection is shortly presented. Acceptable solutions for the enhanced ecological criteria, which are requested by the users of pesticides and consumers of agricultural goods, could be the replacement of classical pesticides by natural products in plant protection. Some natural products are already in use as insecticides, herbicides and fungicides because new biotechnological processes, fermentation and biotransformations provide procedures for their industrial production. In addition to biotechnical processes natural compounds possessing pesticide activities are also prepared by chemical synthesis. An active secondary metabolite must first be isolated from natural sauces and then, based on biological toxicological and ecological studies, acceptable compounds are selected for laboratory and industrial chemical synthesis. Several compounds possessing insecticidal, herbicidal and fungicidal activities, which have been successfully applied for plan protection are presented.

  16. Synthesis of oxazole, oxazoline and isoxazoline derived marine natural products: A review

    Digital Repository Service at National Institute of Oceanography (India)

    Tilvi, S.; Singh, K.S.

    BuLi, -78 ºC - > 0 ºC then: BH3.NH3, 2. Dess-Martin periodinane, dry CH2Cl2 (76% over 2 steps); c) 1. CBr4, PPh3 (77%), 2. nBuLi, THF at -78 ºC then (HCHO)n (90%), 3. EtO 2CCl, pyridine (95%), 4. Ti(OiPr)4, iPrMgCl, Et2 O then: nBu3SnCl at -78 ºC (90... OHMeO O NHO O O N O O O OH O (+)-Phorboxazole A Br N CHO MeOAcOOMeO O HO OMe O N O N O N O Ulapualide A Figure 2. Structures of some oxazole containing marine natural products 2.1 Monoxazole: 2.1.1 Martefragin A (I) The sea alga Martensia fragilis...

  17. Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

    Directory of Open Access Journals (Sweden)

    Werner Telle

    2014-02-01

    Full Text Available The marine natural product malevamide D from the cyanobacterium Symploca hydnoides was synthesized for the first time. The final peptide coupling linked the dolaisoleuine and dolaproine subunits. The phenyl group of malevamide D was also functionalized with a photoreactive diazirine moiety, which was carried through seven reaction steps. Comprehensive assessment of the cytotoxicity in a panel of 42 human cancer cell lines revealed a geomean IC70 value of 1.5 nM (IC50 0.7 nM for malevamide D, whereas the photoreactive derivative proved to be less active by a factor of at least 200. COMPARE analysis indicated tubulin interaction as likely mode of action of malevamide D.

  18. Isolation, biological activity, synthesis, and medicinal chemistry of the pederin/mycalamide family of natural products.

    Science.gov (United States)

    Mosey, R Adam; Floreancig, Paul E

    2012-09-01

    This review highlights the broad range of science that has arisen from the isolation of pederin, the mycalamides, theopederins, and onnamides, and psymberin. Specific topics include structure determination, biological activity, synthesis, and analog preparation and analysis.

  19. Economical synthesis of 13C-labeled opiates, cocaine derivatives and selected urinary metabolites by derivatization of the natural products.

    Science.gov (United States)

    Karlsen, Morten; Liu, Huiling; Johansen, Jon Eigill; Hoff, Bård Helge

    2015-03-25

    The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, (13)C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-(13)C4]heroin, [acetyl-(13)C4-methyl-(13)C]heroin, [acetyl-(13)C2-methyl-(13)C]6-acetylmorphine, [N-methyl-(13)C-O-metyl-(13)C]codeine and phenyl-(13)C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying (13)C atom-efficient routes towards these derivatives. Therefore, the (13)C-labeled opiates and cocaine derivatives were made from the corresponding natural products.

  20. S-(+)-carvone as starting material in the enantioselective synthesis of natural products.

    NARCIS (Netherlands)

    Verstegen-Haaksma, A.A.

    1994-01-01

    In this thesis the applicability of S-(+)-carvone as chiral starting material in the synthesis of biologically active compounds is examined. S-(+)-carvone is the major compound of caraway essential oil. The essential oil content of caraway seed may vary from 2-7% and it contains about 50-60% of S-(+

  1. Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

    DEFF Research Database (Denmark)

    Madsen, Charlotte Marie; Clausen, Mads Hartvig

    2011-01-01

    Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...

  2. Acid-mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

    Directory of Open Access Journals (Sweden)

    Katsunori Tanaka

    2009-08-01

    Full Text Available Microfluidic conditions were applied to acid-mediated reactions, namely, glycosylation, reductive opening of the benzylidene acetal groups, and dehydration, which are the keys to the practical synthesis of N-glycans and the immunostimulating natural product, pristane. A distinctly different reactivity from that in conventional batch stirring was found; the vigorous micromixing of the reactants with the concentrated acids is critical especially for the “fast” reactions to be successful. Such a common feature might be due to the integration of all favorable aspects of microfluidic conditions, i.e., efficient mixing, precise temperature control, and the easy handling of the reactive intermediate by controlling the residence time. The microfluidic reactions cited in this review indicate the need to reinvestigate the traditional or imaginary reactions which have so far been performed and evaluated only in batch apparatus, and therefore they could be recognized as a new strategy in synthesizing natural products of prominent biological activity in a “practical” and a “industrial” manner.

  3. Redirecting photosynthetic electron flow into light-driven synthesis of alternative products including high-value bioactive natural compounds.

    Science.gov (United States)

    Lassen, Lærke Münter; Nielsen, Agnieszka Zygadlo; Ziersen, Bibi; Gnanasekaran, Thiyagarajan; Møller, Birger Lindberg; Jensen, Poul Erik

    2014-01-17

    Photosynthesis in plants, green algae, and cyanobacteria converts solar energy into chemical energy in the form of ATP and NADPH, both of which are used in primary metabolism. However, often more reducing power is generated by the photosystems than what is needed for primary metabolism. In this review, we discuss the development in the research field, focusing on how the photosystems can be used as synthetic biology building blocks to channel excess reducing power into light-driven production of alternative products. Plants synthesize a large number of high-value bioactive natural compounds. Some of the key enzymes catalyzing their biosynthesis are the cytochrome P450s situated in the endoplasmic reticulum. However, bioactive compounds are often synthesized in low quantities in the plants and are difficult to produce by chemical synthesis due to their often complex structures. Through a synthetic biology approach, enzymes with a requirement for reducing equivalents as cofactors, such as the cytochrome P450s, can be coupled directly to the photosynthetic energy output to obtain environmentally friendly production of complex chemical compounds. By relocating cytochrome P450s to the chloroplasts, reducing power can be diverted toward the reactions catalyzed by the cytochrome P450s. This provides a sustainable production method for high-value compounds that potentially can solve the problem of NADPH regeneration, which currently limits the biotechnological uses of cytochrome P450s. We describe the approaches that have been taken to couple enzymes to photosynthesis in vivo and to photosystem I in vitro and the challenges associated with this approach to develop new green production platforms.

  4. Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

    NARCIS (Netherlands)

    Mudit, M.; Khanfar, M.; Muralidharan, A.; Thomas, S.; Shah, G.V.; van Soest, R.W.M.; El Sayed, K.A.

    2009-01-01

    The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl)hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the synthetic

  5. A Common Precursor Approach to Structurally Diverse Natural Products: The Synthesis of the Core Structure of (±)-Clausenamide and the Total Synthesis of (±)-Hyalodendrin

    OpenAIRE

    Szulc, B. R.; Sil, B. C.; Ruiz, A; Hilton, S. T.

    2015-01-01

    Structurally diverse natural products from unrelated sources typically require the development of individual synthetic routes. In a novel approach, we have shown that the epidithiodiketopiperazine-derived natural product (±)-hyalodendrin and the core structure of the unrelated pyrrolidine-derived natural product clausenamide can be synthesised from a common synthetic precursor in good yield by simple variation of the reaction conditions.

  6. α-Carbonyl Radical Cyclization for the Total Synthesis of Natural Products

    Institute of Scientific and Technical Information of China (English)

    SHA Chin-Kang; CHIU Rei-Torng; LIH Shinn-Horng; SANTHOSH K. C.; CHANG Ching-Jung; TSENG Wei-Hong; HO Wen-Yueh

    2003-01-01

    @@ Intramolecular radical cyclization reactions are now used routinely to synthesize carbocyclic and heterocyclicstructures. We have reported that α-carbonyl radicals 1, generated from the corresponding iodo ketones or enones,underwent intramolecular radical cyclization smoothly to afford products 2. [1,2

  7. Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A

    Directory of Open Access Journals (Sweden)

    Bin Xiao

    2014-02-01

    Full Text Available A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 3–14. Compound 7 showed significant PPAR-γ activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-γ activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-γ with EC50 values of 0.67 μM and 0.028 μM, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-γ ligands.

  8. Natural and edible biopolymer poly-gamma-glutamic acid: synthesis, production, and applications.

    Science.gov (United States)

    Sung, Moon-Hee; Park, Chung; Kim, Chul-Joong; Poo, Haryoung; Soda, Kenji; Ashiuchi, Makoto

    2005-01-01

    Poly-gamma-glutamic acid (gamma-PGA) is a very promising biodegradable polymer that is produced by Bacillus subtilis. Gamma-PGA is water-soluble, anionic, biodegradable, and edible. This paper reviews the production of a strain of gamma-PGA and recent developments with respect to applications in terms of Ca absorption, moisturizing properties, gamma-PGA conjugation, super absorbent polymer, and so on. Our recent research shows that gamma-PGA can be used as an immune-stimulating and anti-tumor agent, especially at high molecular weight.

  9. Chemo- and regioselective functionalization of nortrilobolide: application for semi-synthesis of the natural product 2-acetoxytrilobolide

    DEFF Research Database (Denmark)

    Doan, Thi Quynh Nhu; Crestey, François; Olsen, Carl Erik

    2015-01-01

    The difference of reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) is compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the fir...... anticancer agents....

  10. Synthetic glycosylated natural products have satisfactory activities.

    Science.gov (United States)

    Huang, Gangliang; Mei, Xinya

    2014-01-01

    Many natural products contain sugar residues, which are essential components for great medicinal importance. The sugar moieties can improve water-solubility of natural products and decrease their toxicity. At the same time, the glycosidic residues are crucial for the activities of natural products. Much effort has been expended over the past decades in developing novel and efficient methodologies to synthesize the glycosylated natural products. This review highlights recent developments in the synthesis of glycosylated natural products. The structure-activity relationships of some of these glycosylated natural products, together with the structure characteristics of their interaction with the biological targets, are also involved.

  11. Synthesis of All-Z-1,6,9,12,15-Octadecapenten-3-one, A Vinyl Ketone Polyunsaturated Marine Natural Product Isolated from Callysponga sp.

    Directory of Open Access Journals (Sweden)

    Anne Marie Langseter

    2014-03-01

    Full Text Available The synthesis of the marine natural product 1,6Z,9Z,12Z,15Z-octadecapentaen-3-one (1 has been achieved by two different routes starting from the ethyl esters of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, respectively. Using EPA ethyl ester as starting material the polyunsaturated vinyl ketone lipid 1 was obtained in 17% overall yield.

  12. (E)- and (Z)-Stereodefined Enol Sulfate Esters Derived from α-Aryl Aldehydes: Stereocomplementary Synthesis of Styryl Sulfate Natural Products.

    Science.gov (United States)

    Yu, Shuai; Li, Feng; Kim, Sanghee

    2017-07-07

    A method for the stereoselective formation of enol sulfate esters from α-aryl aldehydes is described. This method involved the stereocontrolled enolization of a carbonyl group with DBU or t-BuOK followed by trapping with a reactive sulfuryl imidazolium salt, providing the corresponding styryl enol sulfate esters in good to excellent yields and stereoselectivities. This method was applied to the first total synthesis of the enol sulfate natural products in a stereocomplementary manner.

  13. Synthesis and evaluation of anticancer natural product analogues based on angelmarin: targeting the tolerance towards nutrient deprivation.

    Science.gov (United States)

    Magolan, Jakob; Adams, Nathan B P; Onozuka, Hiroko; Hungerford, Natasha L; Esumi, Hiroyasu; Coster, Mark J

    2012-05-01

    Inspired by nature: Angelmarin is an anticancer natural product with potent antiausterity activity, that is, selective cytotoxicity towards nutrient-deprived, resistant cancer cells. Through structure-activity relationship studies, three analogues were identified as lead compounds for the develpoment of molecular probes for the investigation of the mode of action and biological targets of the antiausterity compounds.

  14. Biology-oriented synthesis of a natural-product inspired oxepane collection yields a small-molecule activator of the Wnt-pathway.

    Science.gov (United States)

    Basu, Sudipta; Ellinger, Bernhard; Rizzo, Stefano; Deraeve, Céline; Schürmann, Markus; Preut, Hans; Arndt, Hans-Dieter; Waldmann, Herbert

    2011-04-26

    In Biology Oriented Synthesis the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is met by the structurally complex scaffolds of natural products (NPs) selected in evolution. The synthesis of NP-inspired compound collections approaching the complexity of NPs calls for the development of efficient synthetic methods. We have developed a one pot 4-7 step synthesis of mono-, bi-, and tricyclic oxepanes that resemble the core scaffolds of numerous NPs with diverse bioactivities. This sequence entails a ring-closing ene-yne metathesis reaction as key step and makes productive use of polymer-immobilized scavenger reagents. Biological profiling of a corresponding focused compound collection in a reporter gene assay monitoring for Wnt-signaling modulation revealed active Wntepanes. This unique class of small-molecule activators of the Wnt pathway modulates the van-Gogh-like receptor proteins (Vangl), which were previously identified in noncanonical Wnt signaling, and acts in synergy with the canonical activator protein (Wnt-3a).

  15. Catalytic Enantioselective Olefin Metathesis in Natural Product Synthesis. Chiral Metal-Based Complexes that Deliver High Enantioselectivity and More

    Science.gov (United States)

    Malcolmson, Steven J.; Meek, Simon J.; Zhugralin, Adil R.

    2012-01-01

    Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure substrates and achiral Mo alkylidenes or Ru-based carbenes. The scope of research towards design and development of chiral catalysts is not limited to discovery of complexes that are merely the chiral versions of the related achiral variants. A chiral olefin metathesis catalyst, in addition to furnishing products of high enantiomeric purity, can offer levels of efficiency, product selectivity and/or olefin stereoselectivity that are unavailable through the achiral variants. Such positive attributes of chiral catalysts (whether utilized in racemic or enantiomerically enriched form) should be considered as general, applicable to other classes of transformations. PMID:19967680

  16. Efficient synthesis of glycosylated phenazine natural products and analogs with DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors

    DEFF Research Database (Denmark)

    Laursen, Jane B.; Petersen, Lars; Jensen, K.J.

    2003-01-01

    Inspired by the occurrence and function of phenazines in natural products, new glycosylated analogs were designed and synthesized. DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors were used in an efficient and easily-handled glycosylation protocol compatible with combinatorial chemistry...

  17. Antiplasmodial Natural Products

    Directory of Open Access Journals (Sweden)

    Cláudio R. Nogueira

    2011-03-01

    Full Text Available Malaria is a human infectious disease that is caused by four species of Plasmodium. It is responsible for more than 1 million deaths per year. Natural products contain a great variety of chemical structures and have been screened for antiplasmodial activity as potential sources of new antimalarial drugs. This review highlights studies on natural products with antimalarial and antiplasmodial activity reported in the literature from January 2009 to November 2010. A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and chromenes are listed in this review.

  18. Synthesis and agrochemical screening of a library of natural product-like bicyclo[2,2,2]octenones.

    Science.gov (United States)

    Smith, Stephen C; James, Donald R; Abelman, Matthew M; Sexton, Graham J

    2005-11-01

    A general route to a series of differentially substituted bicyclo[2,2,2]octenones has been developed, making use of the in situ intramolecular Diels Alder reaction of masked ortho-benzoquinones. This approach was used to synthesize a series of thirteen key acid-containing templates from which a solution phase discovery library of 1126 diverse amides was then constructed. The rigid polycyclic nature of the templates and the prevalence of oxygenated functionality confer natural product-like qualities and three-dimensional diversity. The library was screened in HTS in vivo against a number of weed, insect and fungal model organisms leading to the discovery of a novel series of herbicidally active compounds. The development, production and biological activity of the library are described.

  19. Microbial production of natural raspbery ketone

    NARCIS (Netherlands)

    Beekwilder, M.J.; Meer, van der I.M.; Sibbesen, O.; Broekgaarden, M.; Qvist, I.; Mikkelsen, J.D.; Hall, R.D.

    2007-01-01

    Raspberry ketone is an important compound for the flavour industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be produced by organic synthesis. Demand for natural raspberry ketone is growing considerably. However, this product is

  20. Microbial production of natural raspbery ketone

    NARCIS (Netherlands)

    Beekwilder, M.J.; Meer, van der I.M.; Sibbesen, O.; Broekgaarden, M.; Qvist, I.; Mikkelsen, J.D.; Hall, R.D.

    2007-01-01

    Raspberry ketone is an important compound for the flavour industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be produced by organic synthesis. Demand for natural raspberry ketone is growing considerably. However, this product is extreme

  1. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

    Science.gov (United States)

    Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

    2015-03-06

    Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis.

  2. Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers.

    Science.gov (United States)

    Healy, Alan R; Vinale, Francesco; Lorito, Matteo; Westwood, Nicholas J

    2015-02-06

    The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.

  3. A natural product inspired hybrid approach towards the synthesis of novel pentamidine based scaffolds as potential anti-parasitic agents.

    Science.gov (United States)

    Tyagi, Vikas; Khan, Shahnawaz; Shivahare, Rahul; Srivastava, Khushboo; Gupta, Suman; Kidwai, Saqib; Srivastava, Kumkum; Puri, S K; Chauhan, Prem M S

    2013-01-01

    A natural product inspired molecular hybridization approach led us to a series of novel pentamidine based pyrimidine and chalcone scaffolds. All the hybrids were evaluated for their anti-leishmanial potential. Most of the screened compounds have showed significant in vitro anti-leishmanial activity with less cytotoxicity in comparison to the standard drugs (pentamidine, sodium stibogluconate, and miltefosine). Additionally, anti-malarial screening of these compounds was also done and four compounds have shown superior activity against chloroquine resistance strain (K1) of Plasmodium falciparum.

  4. Natural Products for Antithrombosis

    Directory of Open Access Journals (Sweden)

    Cen Chen

    2015-01-01

    Full Text Available Thrombosis is considered to be closely related to several diseases such as atherosclerosis, ischemic heart disease and stroke, as well as rheumatoid arthritis, hyperuricemia, and various inflammatory conditions. More and more studies have been focused on understanding the mechanism of molecular and cellular basis of thrombus formation as well as preventing thrombosis for the treatment of thrombotic diseases. In reality, there is considerable interest in the role of natural products and their bioactive components in the prevention and treatment of thrombosis related disorders. This paper briefly describes the mechanisms of thrombus formation on three aspects, including coagulation system, platelet activation, and aggregation, and change of blood flow conditions. Furthermore, the natural products for antithrombosis by anticoagulation, antiplatelet aggregation, and fibrinolysis were summarized, respectively.

  5. Rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes and CO: reaction design, development, application in natural product synthesis, and inspiration for developing new reactions for synthesis of eight-membered carbocycles.

    Science.gov (United States)

    Wang, Yi; Yu, Zhi-Xiang

    2015-08-18

    Practical syntheses of natural products and their analogues with eight-membered carbocyclic skeletons are important for medicinal and biological investigations. However, methods and strategies to construct the eight-membered carbocycles are limited. Therefore, developing new methods to synthesize the eight-membered carbocycles is highly desired. In this Account, we describe our development of three rhodium-catalyzed cycloadditions for the construction of the eight-membered carbocycles, which have great potential in addressing the challenges in the synthesis of medium-sized ring systems. The first reaction described in this Account is our computationally designed rhodium-catalyzed two-component [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and CO for the diastereoselective construction of bi- and tricyclic cyclooctenones. The design of this reaction is based on the hypothesis that the C(sp(3))-C(sp(3)) reductive elimination of the eight-membered rhodacycle intermediate generated from the rhodium-catalyzed cyclopropane cleavage and alkene insertion, giving Wender's [5 + 2] cycloadduct, is not easy. Under CO atmosphere, CO insertion may occur rapidly, converting the eight-membered rhodacycle into a nine-membered rhodacycle, which then undergoes an easy C(sp(2))-C(sp(3)) reductive elimination process and furnishes the [5 + 2 + 1] product. This hypothesis was supported by our preliminary DFT studies and also served as inspiration for the development of two [7 + 1] cycloadditions: the [7 + 1] cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs) and CO for the construction of cyclooctadienones, and the benzo/[7 + 1] cycloaddition of cyclopropyl-benzocyclobutenes (CP-BCBs) and CO to synthesize the benzocyclooctenones. The efficiency of these rhodium-catalyzed cycloadditions can be revealed by the application in natural product synthesis. Two eight-membered ring-containing natural products, (±)-asterisca-3(15),6-diene and (+)-asteriscanolide, have been

  6. Leloir Glycosyltransferases and Natural Product Glycosylation: Biocatalytic Synthesis of the C-Glucoside Nothofagin, a Major Antioxidant of Redbush Herbal Tea.

    Science.gov (United States)

    Bungaruang, Linda; Gutmann, Alexander; Nidetzky, Bernd

    2013-10-11

    Nothofagin is a major antioxidant of redbush herbal tea and represents a class of bioactive flavonoid-like C-glycosidic natural products. We developed an efficient enzymatic synthesis of nothofagin based on a one-pot coupled glycosyltransferase-catalyzed transformation that involves perfectly selective 3'-C-β-d-glucosylation of naturally abundant phloretin and applies sucrose as expedient glucosyl donor. C-Glucosyltransferase from Oryza sativa (rice) was used for phloretin C-glucosylation from uridine 5'-diphosphate (UDP)-glucose, which was supplied continuously in situ through conversion of sucrose and UDP catalyzed by sucrose synthase from Glycine max (soybean). In an evaluation of thermodynamic, kinetic, and stability parameters of the coupled enzymatic reactions, poor water solubility of the phloretin acceptor substrate was revealed as a major bottleneck of conversion efficiency. Using periodic feed of phloretin controlled by reaction progress, nothofagin concentrations (45 mM; 20 g l(-1)) were obtained that vastly exceed the phloretin solubility limit (5-10 mM). The intermediate UDP-glucose was produced from catalytic amounts of UDP (1.0 mM) and was thus recycled 45 times in the process. Benchmarked against comparable glycosyltransferase-catalyzed transformations (e.g., on quercetin), the synthesis of nothofagin has achieved intensification in glycosidic product formation by up to three orders of magnitude (μM→mM range). It thus makes a strong case for the application of Leloir glycosyltransferases in biocatalytic syntheses of glycosylated natural products as fine chemicals.

  7. Synthesis of ent-BE-43547A1 reveals a potent hypoxia-selective anticancer agent and uncovers the biosynthetic origin of the APD-CLD natural products

    Science.gov (United States)

    Villadsen, Nikolaj L.; Jacobsen, Kristian M.; Keiding, Ulrik B.; Weibel, Esben T.; Christiansen, Bjørn; Vosegaard, Thomas; Bjerring, Morten; Jensen, Frank; Johannsen, Mogens; Tørring, Thomas; Poulsen, Thomas B.

    2017-03-01

    Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration. Discrepancies between the spectroscopic signatures of the synthetic compounds with that originally reported for the BE-43547 members stimulated us to re-isolate the natural product from a BE-43547-producing microorganism during which we elucidated the biosynthetic gene clusters for the BE-43547 family as well as for all other known APD-CLDs. Our studies underline the exciting possibilities for the further development of the anticancer activities of these natural products.

  8. New Synthetic Methods for Hypericum Natural Products

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Insik [Iowa State Univ., Ames, IA (United States)

    2006-01-01

    Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

  9. Flow chemistry syntheses of natural products.

    Science.gov (United States)

    Pastre, Julio C; Browne, Duncan L; Ley, Steven V

    2013-12-07

    The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.

  10. Natural products--a simple model to explain chemical diversity.

    Science.gov (United States)

    Firn, Richard D; Jones, Clive G

    2003-08-01

    A simple evolutionary model is presented which explains why organisms produce so many natural products, why so many have low biological activity, why enzymes involved in natural product synthesis have the properties they do and why natural product metabolism is shaped as it is.

  11. A practical synthesis of long-chain iso-fatty acids (iso-C12-C19) and related natural products.

    Science.gov (United States)

    Richardson, Mark B; Williams, Spencer J

    2013-01-01

    A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C15-C17) and hexadecanolide (for iso-C18-C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

  12. A practical synthesis of long-chain iso-fatty acids (iso-C12–C19 and related natural products

    Directory of Open Access Journals (Sweden)

    Mark B. Richardson

    2013-09-01

    Full Text Available A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12–C19 was developed commencing with methyl undec-10-enoate (methyl undecylenate (for iso-C12–C14 or the C15 and C16 lactones pentadecanolide (for iso-C15–C17 and hexadecanolide (for iso-C18–C19. Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13–C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S-2,15-dimethylpalmitic acid, (S-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

  13. Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products dictyostatin, discodermolide, and taxol.

    Science.gov (United States)

    Paterson, Ian; Naylor, Guy J; Gardner, Nicola M; Guzmán, Esther; Wright, Amy E

    2011-02-01

    The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule-stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22-membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide-derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late-stage diversification strategy and the construction of a small library of methyl-ether derivatives, along with the first triple hybrids bearing the side-chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti-proliferative activity of these compounds in a series of human cancer cell lines, including the taxol-resistant NCI/ADR-Res cell line, allowed the proposal of various structure-activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin.

  14. Feature-aware natural texture synthesis

    KAUST Repository

    Wu, Fuzhang

    2014-12-04

    This article presents a framework for natural texture synthesis and processing. This framework is motivated by the observation that given examples captured in natural scene, texture synthesis addresses a critical problem, namely, that synthesis quality can be affected adversely if the texture elements in an example display spatially varied patterns, such as perspective distortion, the composition of different sub-textures, and variations in global color pattern as a result of complex illumination. This issue is common in natural textures and is a fundamental challenge for previously developed methods. Thus, we address it from a feature point of view and propose a feature-aware approach to synthesize natural textures. The synthesis process is guided by a feature map that represents the visual characteristics of the input texture. Moreover, we present a novel adaptive initialization algorithm that can effectively avoid the repeat and verbatim copying artifacts. Our approach improves texture synthesis in many images that cannot be handled effectively with traditional technologies.

  15. Super Natural II--a database of natural products.

    Science.gov (United States)

    Banerjee, Priyanka; Erehman, Jevgeni; Gohlke, Björn-Oliver; Wilhelm, Thomas; Preissner, Robert; Dunkel, Mathias

    2015-01-01

    Natural products play a significant role in drug discovery and development. Many topological pharmacophore patterns are common between natural products and commercial drugs. A better understanding of the specific physicochemical and structural features of natural products is important for corresponding drug development. Several encyclopedias of natural compounds have been composed, but the information remains scattered or not freely available. The first version of the Supernatural database containing ∼ 50,000 compounds was published in 2006 to face these challenges. Here we present a new, updated and expanded version of natural product database, Super Natural II (http://bioinformatics.charite.de/supernatural), comprising ∼ 326,000 molecules. It provides all corresponding 2D structures, the most important structural and physicochemical properties, the predicted toxicity class for ∼ 170,000 compounds and the vendor information for the vast majority of compounds. The new version allows a template-based search for similar compounds as well as a search for compound names, vendors, specific physical properties or any substructures. Super Natural II also provides information about the pathways associated with synthesis and degradation of the natural products, as well as their mechanism of action with respect to structurally similar drugs and their target proteins.

  16. Marine Natural Products Against Tuberculosis

    Directory of Open Access Journals (Sweden)

    Marcus Vinícius Nora De Souza

    2006-01-01

    Full Text Available Natural products represent an outstanding source of compounds that play an important role in the treatment of human diseases. Due to the importance of nature as a source of new drug candidates, the aim of this review is to highlight the marine natural products, which exhibit antituberculosis activity, discovered between 2000 and 2005.

  17. Suggestion of transform synthesis ammonia co-production natural gas remission imbalance between supply and demand%改造合成氨联产天然气缓解供需矛盾的建议

    Institute of Scientific and Technical Information of China (English)

    李志坚; 温倩

    2014-01-01

    通过对我国合成氨和天然气产业现状的分析,提出了合成氨联产天然气的初步改造方案,并进行了经济分析,预测了改造效果和提出了政策建议。%The paper analyzes industry status quo of synthesis ammonia and natural gas in China, proposes preliminary modification scheme of synthesis ammonia co-production natural gas, it also processes economic analysis and forecasts reforestation effect, at last, it proposes policy suggestion.

  18. 用反Diels-Alder反应合成天然产物%Natural Products Synthesis by Retro- Diels- Alder Reaction

    Institute of Scientific and Technical Information of China (English)

    刘志煜; 褚新阶; 何菱; 谢益农; 赵联运

    1997-01-01

    Stereospecific introduction of functionalities and substituents on the cyclopentenone ring in the rigid molecule tricyclo [ 5.2.1.02,6] decadineone 1 followed by Retro - Diels - Alder reaction produced the cyclopentenone derivatives 6,7,14,22 and 29, which were converted into chromomoric acid C-I 2, D-I 3, F 4, B 7, 18 invictolide and 6 - epiinvictolide 19 as well as a key intermediate 30for further synthesis of macrocyclic pyrrolizidine alkaloid merenskine 27.%天然产物全合成主要在于发展有效的方法以组成碳骨架和立体控制引入必须的官能团.本文利用刚性分子三环癸二烯酮(1)为原料,立体控制地引入取代基及官能团组成目标分子所需的碳骨架及官能团后进行反Diels-Alder反应释放出取代环戊烯酮,从而进一步合成目标分子克罗莫酸C-I 2,D-I 3,F 4,B 7,蚊皇识别信息索18,6-表蚊皇识别信息素19以及经30获得的32,后者是全合成大环内酯生物碱27的关键中间体.用酶催化反应不对称乙酰化内消旋二醇24c得光学活性单乙酯24d(81%产率,98.3%对映体过量值).24d经过官能团转换可得(+)及(-)1,从(-)1用相似的反应合成了光学活性蚁皇识别信息素(18).

  19. Antibacterial natural products in medicinal chemistry--exodus or revival?

    Science.gov (United States)

    von Nussbaum, Franz; Brands, Michael; Hinzen, Berthold; Weigand, Stefan; Häbich, Dieter

    2006-08-04

    To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.

  20. Combustion synthesis method and products

    Science.gov (United States)

    Holt, J.B.; Kelly, M.

    1993-03-30

    Disclosed is a method of producing dense refractory products, comprising: (a) obtaining a quantity of exoergic material in powder form capable of sustaining a combustion synthesis reaction; (b) removing absorbed water vapor therefrom; (c) cold-pressing said material into a formed body; (d) plasma spraying said formed body with a molten exoergic material to form a coat thereon; and (e) igniting said exoergic coated formed body under an inert gas atmosphere and pressure to produce self-sustained combustion synthesis. Also disclosed are products produced by the method.

  1. Synthesis of Natural Cyclopentapeptides Isolated from Dianthus chinensis.

    Science.gov (United States)

    Zhang, Shengping; Amso, Zaid; De Leon Rodriguez, Luis M; Kaur, Harveen; Brimble, Margaret A

    2016-07-22

    The first syntheses of the naturally occurring cyclic peptides dianthin I (1), pseudostellarin A (2), and heterophyllin J (3) are described. The linear protected peptide precursors were prepared efficiently via Fmoc-solid-phase synthesis and subsequently cyclized in solution under dilute conditions. The structures of the synthetic cyclopentapeptides were confirmed by NMR spectroscopy and mass spectrometry and were in agreement with the literature data reported for the natural products.

  2. Natural products in chemical biology

    National Research Council Canada - National Science Library

    Civjan, Natanya

    2012-01-01

    "Based on the award winning Wiley Encyclopedia of Chemical Biology, this book provides a general overview of the unique features of the small molecules referred to as "natural products", explores how...

  3. Natural production of biological optical systems

    Science.gov (United States)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  4. Ibuprofen: Synthesis, production and properties

    Directory of Open Access Journals (Sweden)

    Mijin Dušan Ž.

    2003-01-01

    Full Text Available Since its introduction in 1969, ibuprofen has become one of the most common painkillers in the world. Ibuprofen in an NSAID (non-steroidal anti-inflammatory drug and like other drugs of its class it possesses analgetic, antipyretic and anti-inflammatory properties. While ibuprofen is a relatively simple molecule, there is still sufficient structural complexity to ensure that a large number of different synthetic approaches are possible. Since the introduction of pharmaceutical products containing ibuprofen, industrial and academic scientists have developed many potential production processes. This paper describes the history, synthesis and production, as well as the properties and stability of ibuprofen.

  5. (+-Discodermolide: A Marine Natural Product Against Cancer

    Directory of Open Access Journals (Sweden)

    Marcus Viníus Nora De Souza

    2004-01-01

    Full Text Available (+-Discodermolide was isolated in 1990 by Gunasekera et al. from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol® that has become the best-selling anticancer drug in history. Taxol is also the first natural product described that stabilizes the microtubules involved in many aspects of cellular biology and that represent an important target of anticancer chemotherapeutics. However, (+-discodermolide appears to be far more potent than Taxol® against tumors that have developed multiple-drug resistance, with an IC50 in the low nanomolar range. Due to these excellent results, this natural product was licensed to Novartis Pharmaceutical Corporation in early 1998. The present review covers the history, biological activity, total synthesis, and synthetic analogs of (+-discodermolide.

  6. (+)-discodermolide: a marine natural product against cancer.

    Science.gov (United States)

    De Souza, Marcus Vinícius Nora

    2004-06-11

    (+)-discodermolide was isolated in 1990 by Gunasekera et al. from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol that has become the best-selling anticancer drug in history. Taxol is also the first natural product described that stabilizes the microtubules involved in many aspects of cellular biology and that represent an important target of anticancer chemotherapeutics. However, (+)-discodermolide appears to be far more potent than Taxol against tumors that have developed multiple-drug resistance, with an IC50 in the low nanomolar range. Due to these excellent results, this natural product was licensed to Novartis Pharmaceutical Corporation in early 1998. The present review covers the history, biological activity, total synthesis, and synthetic analogs of (+)-discodermolide.

  7. The chemistry of isoindole natural products

    Directory of Open Access Journals (Sweden)

    Klaus Speck

    2013-10-01

    Full Text Available This review highlights the chemical and biological aspects of natural products containing an oxidized or reduced isoindole skeleton. This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids, the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well.

  8. Microbial production of natural raspberry ketone.

    Science.gov (United States)

    Beekwilder, Jules; van der Meer, Ingrid M; Sibbesen, Ole; Broekgaarden, Mans; Qvist, Ingmar; Mikkelsen, Joern D; Hall, Robert D

    2007-10-01

    Raspberry ketone is an important compound for the flavour industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be produced by organic synthesis. Demand for "natural" raspberry ketone is growing considerably. However, this product is extremely expensive. Consequently, there is a remaining desire to better understand how raspberry ketone is synthesized in vivo, and which genes and enzymes are involved. With this information we will then be in a better position to design alternative production strategies such as microbial fermentation. This article focuses on the identification and application of genes potentially linked to raspberry ketone synthesis. We have isolated candidate genes from both raspberry and other plants, and these have been introduced into bacterial and yeast expression systems. Conditions have been determined that result in significant levels of raspberry ketone, up to 5 mg/L. These results therefore lay a strong foundation for a potentially renewable source of "natural" flavour compounds making use of plant genes.

  9. The isolation, total synthesis and structure elucidation of chlorofusin, a natural product inhibitor of the p53-MDM2 protein-protein interaction

    Science.gov (United States)

    Clark, Ryan C.; Lee, Sang Yeul; Searcey, Mark; Boger, Dale L.

    2009-01-01

    Inhibitors of key protein-protein interactions are emerging as exciting therapeutic targets for the treatment of cancer. One such interaction between MDM2 (HDM2) and p53, that silences the tumour suppression activities of p53, was found to be inhibited by the recently isolated natural product chlorofusin. Synthetic studies on this complex natural product summarized herein have served to reassign its chromophore relative stereochemistry, assign its absolute stereochemistry, and provided access to a series of key analogues and partial structures for biological evaluation. PMID:19642417

  10. Architectural self-construction in nature and chemical synthesis.

    Science.gov (United States)

    Sorensen, Erik J

    2003-07-31

    The chemistry of squalene oxide (1) exemplifies that architectural complexity can be encoded in the structures of relatively simple, polyunsaturated molecules. When the concept of architectural self-construction is an integral part of the design of a chemical synthesis, powerful strategies can be uncovered. this article addresses studies which showed that polyunsaturated, 19-membered ring carbocycle contains all of the molecular information that is required to give the stereochemically complex polycyclic architecture of the cytotoxic natural product FR182877.

  11. Natural Products from Mangrove Actinomycetes

    Directory of Open Access Journals (Sweden)

    Dong-Bo Xu

    2014-05-01

    Full Text Available Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.

  12. Natural products from filamentous fungi and production by heterologous expression.

    Science.gov (United States)

    Alberti, Fabrizio; Foster, Gary D; Bailey, Andy M

    2017-01-01

    Filamentous fungi represent an incredibly rich and rather overlooked reservoir of natural products, which often show potent bioactivity and find applications in different fields. Increasing the naturally low yields of bioactive metabolites within their host producers can be problematic, and yield improvement is further hampered by such fungi often being genetic intractable or having demanding culturing conditions. Additionally, total synthesis does not always represent a cost-effective approach for producing bioactive fungal-inspired metabolites, especially when pursuing assembly of compounds with complex chemistry. This review aims at providing insights into heterologous production of secondary metabolites from filamentous fungi, which has been established as a potent system for the biosynthesis of bioactive compounds. Numerous advantages are associated with this technique, such as the availability of tools that allow enhanced production yields and directing biosynthesis towards analogues of the naturally occurring metabolite. Furthermore, a choice of hosts is available for heterologous expression, going from model unicellular organisms to well-characterised filamentous fungi, which has also been shown to allow the study of biosynthesis of complex secondary metabolites. Looking to the future, fungi are likely to continue to play a substantial role as sources of new pharmaceuticals and agrochemicals-either as producers of novel natural products or indeed as platforms to generate new compounds through synthetic biology.

  13. System of Natural Health Products

    Directory of Open Access Journals (Sweden)

    Angelica Paoletti

    2011-01-01

    Full Text Available Introduction. The safety of vitamin K antagonists (VKA use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to “natural health” products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n=3 and acenocoumarol (n=4, and 5 cases of INR increase (all warfarin associated. It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA.

  14. Harnessing natural product assembly lines: structure, promiscuity, and engineering.

    Science.gov (United States)

    Ladner, Christopher C; Williams, Gavin J

    2016-03-01

    Many therapeutically relevant natural products are biosynthesized by the action of giant mega-enzyme assembly lines. By leveraging the specificity, promiscuity, and modularity of assembly lines, a variety of strategies has been developed that enables the biosynthesis of modified natural products. This review briefly summarizes recent structural advances related to natural product assembly lines, discusses chemical approaches to probing assembly line structures in the absence of traditional biophysical data, and surveys efforts that harness the inherent or engineered promiscuity of assembly lines for the synthesis of non-natural polyketides and non-ribosomal peptide analogues.

  15. Glycosylation and Activities of Natural Products.

    Science.gov (United States)

    Huang, Gangliang; Lv, Meijiao; Hu, Jinchuan; Huang, Kunlin; Xu, Hong

    2016-01-01

    Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products.

  16. Natural products as antimitotic agents.

    Science.gov (United States)

    Dall'Acqua, Stefano

    2014-01-01

    Natural products still play an important role in the medicinal chemistry, especially in some therapeutic areas. As example more than 60% of currently-used anticancer agents are derives from natural sources including plants, marine organisms or micro-organism. Thus natural products (NP) are an high-impact source of new "lead compounds" or new potential therapeutic agents despite the large development of biotechnology and combinatorial chemistry in the drug discovery and development. Many examples of anticancer drugs as paclitaxel, combretastatin, bryostatin and discodermolide have shown the importance of NP in the anticancer chemotherapy through many years. Many organisms have been studied as sources of drugs namely plants, micro-organisms and marine organisms and the obtained NP can be considered a group of "privileged chemical structures" evolved in nature to interact with other organisms. For this reason NP are a good starting points for pharmaceutical research and also for library design. Tubulin and microtubules are one of the most studied targets for the search of anticancer compounds. Microtubule targeting agents (MTA) also named antimitotic agents are compounds that are able to perturb mitosis but are also able to arrest cell growing during interphase. The anticancer drugs, taxanes and vinca alkaloids have established tubulin as important target in cancer therapy. More recently the vascular disrupting agents (VDA) combretastatin analogues were studied for their antimitotics properties. This review will consider the anti mitotic NP and their potential impact in the development of new therapeutic agents.

  17. Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

    Directory of Open Access Journals (Sweden)

    Hiroaki Suga

    2013-03-01

    Full Text Available In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>1012, affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID system, including the recent identification of inhibitors against various therapeutic targets.

  18. Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

    Directory of Open Access Journals (Sweden)

    Catalin V. Maftei

    2013-10-01

    Full Text Available Taking into consideration the biological activity of the only natural products containing a 1,2,4-oxadiazole ring in their structure (quisqualic acid and phidianidines A and B, the natural product analogs 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-ylphenylpyrrolidine-2,5-dione (4 and 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-ylphenyl-1H-pyrrole-2,5-dione (7 were synthesized starting from 4-(3-tert-butyl-1,2,4-oxadiazol-5-ylaniline (1 in two steps by isolating the intermediates 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-ylphenylamino-4-oxobutanoic acid (3 and (Z-4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-ylphenylamino-4-oxobut-2-enoic acid (6. The two natural product analogs 4 and 7 were then tested for antitumor activity toward a panel of 11 cell lines in vitro by using a monolayer cell-survival and proliferation assay. Compound 7 was the most potent and exhibited a mean IC50 value of approximately 9.4 µM. Aniline 1 was synthesized by two routes in one-pot reactions starting from tert-butylamidoxime and 4-aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography.

  19. Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

    Science.gov (United States)

    Maftei, Catalin V; Fodor, Elena; Jones, Peter G; Franz, M Heiko; Kelter, Gerhard; Fiebig, Heiner

    2013-01-01

    Summary Taking into consideration the biological activity of the only natural products containing a 1,2,4-oxadiazole ring in their structure (quisqualic acid and phidianidines A and B), the natural product analogs 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenyl)pyrrolidine-2,5-dione (4) and 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenyl)-1H-pyrrole-2,5-dione (7) were synthesized starting from 4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)aniline (1) in two steps by isolating the intermediates 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobutanoic acid (3) and (Z)-4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobut-2-enoic acid (6). The two natural product analogs 4 and 7 were then tested for antitumor activity toward a panel of 11 cell lines in vitro by using a monolayer cell-survival and proliferation assay. Compound 7 was the most potent and exhibited a mean IC50 value of approximately 9.4 µM. Aniline 1 was synthesized by two routes in one-pot reactions starting from tert-butylamidoxime and 4-aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography. PMID:24222789

  20. Natural and Heterologous Production of Bacteriocins

    Science.gov (United States)

    Cintas, Luis M.; Herranz, Carmen; Hernández, Pablo E.

    Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria, and their use as natural and nontoxic food preservatives has been the source of considerable interest for the research community. In addition, bacteriocins have been investigated for their potential use in human and veterinary applications and in the animal production field. In the native bacterial strain, most bacteriocins are synthesized as biologically inactive precursors, with N-terminal extensions, that are cleaved concomitantly during export of the bacteriocin by dedicated ABC transporters, or the general secretory pathway (GSP) or Sec-dependent pathway. However, a few bacteriocins are synthesized without an N-terminal extension, and others are circularized through a head-to-tail peptide bond, complicating the elucidation of their processing and transport across the cytoplasmic membrane. The high cost of synthetic bacteriocin synthesis and their low yields from many natural producers recommends the exploration of recombinant microbial systems for the heterologous production of bacteriocins. Other advantages of such systems include production of bacteriocins in safer hosts, increased bacteriocin production, control of bacteriocin gene expression, production of food ingredients with antimicrobial activity, construction of multibacteriocinogenic strains with a wider antagonistic spectrum, a better adaptation of the selected hosts to food environments, and providing antagonistic properties to lactic acid bacteria (LAB) used as starter, protective, or probiotic cultures. The recombinant production of bacteriocins mostly relies on the use of expression vectors that replicate in Gram-negative bacteria, Gram-positive bacteria, and yeasts, whereas the production of bacteriocins in heterologous LAB hosts may be essentially based on the expression of native biosynthetic genes, by exchanging or replacing leader peptides and/or dedicated processing and secretion systems (ABC transporters

  1. Process Parameters Affecting the Synthesis of Natural Flavors by Shiitake (Lentinula edodes during the Production of a Non-Alcoholic Beverage

    Directory of Open Access Journals (Sweden)

    Sibel Özdemir

    2017-04-01

    Full Text Available A novel alcohol-free beverage with a fruity, slightly sour, sweetish, fresh, and plum-like flavor was produced by incorporating the edible mushroom shiitake (Lentinula edodes into the fermentation process. Shiitake pellets were used as a biocatalyst to promote the synthesis of the fruity esters methyl 2-methylbutanoate and 2-phenylethanol from amino acids and an organic acid present in the wort. We investigated the impact of two critical process parameters (volumetric power input and inoculum concentration on the morphology of, and flavor production by, the shiitake pellets in a 1 L stirred bioreactor. Increasing the volumetric power input and biomass concentration influenced the morphology of the pellets and promoted the production of the most important flavor compound methyl 2-methylbutanoate in the beverage. Furthermore the worty off-flavor methional was degraded during the cultivation in stirred bioreactor by shiitake pellets. These findings provide useful information to facilitate the scale-up of the biotransformation and fermentation process in bioreactors.

  2. Disorders of primary metabolites in response to drought may increase the synthesis of natural products for medicinal purposes: South American herbs - a case study.

    Science.gov (United States)

    Martim, Silvia Aparecida

    2014-01-01

    The use of plants for healing diseases is one of the oldest medical practices and there are several studies showing that botany and medicine are related. Recent researches have shown that around 25% of new chemical entities and 42% of anticancer drugs marketed worldwide from 1981 to 2006 are obtained from natural products and their derivatives. One-third of the botanical biodiversity of the planet is in South American tropical ecosystems (Neotropical). Over the centuries, plants have been used by indigenous people for curing diseases. This strong tradition has been a great challenge for the scientific community in order to validate the folkloric medicinal use of herbs. In this way, a very few Neotropical pharmaceutical products have reached the market in industrialized countries, even though they have a considerable plant diversity. Plants synthesize several organic compounds which are not related to their growth and development and are called secondary metabolites or natural products that are derived from central or primary metabolism. Because plants are sessile organisms, they have to respond quickly to environmental changes in order to escape and survive under unfavorable conditions. Drought is one of the most worldwide serious impediments for crop yields producing adverse negative effects on plant growth, by impacting leaves and roots growth, stomatal conductance, photosynthetic rate and biomass gain. The three major classes of secondary metabolites are produced from pathways of different primary metabolites, including glycolysis, tricarboxilic acid cycle, aliphatic amino acids, pentose phosphate pathway, shikimate pathway and aromatic amino acids. This review compiles the metabolic changes occurring at primary metabolite level and total biosynthesis of natural products with potential for the development of new drugs in response to drought.

  3. Metabolomics and dereplication strategies in natural products.

    Science.gov (United States)

    Tawfike, Ahmed Fares; Viegelmann, Christina; Edrada-Ebel, Ruangelie

    2013-01-01

    Metabolomic methods can be utilized to screen diverse biological sources of potentially novel and sustainable sources of antibiotics and pharmacologically-active drugs. Dereplication studies by high resolution Fourier transform mass spectrometry coupled to liquid chromatography (LC-HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy can establish the chemical profile of endophytic and/or endozoic microbial extracts and their plant or animal sources. Identifying the compounds of interest at an early stage will aid in the isolation of the bioactive components. Therefore metabolite profiling is important for functional genomics and in the search for new pharmacologically active compounds. Using the tools of metabolomics through the employment of LC-HRFTMS as well as high resolution NMR will be a very efficient approach. Metabolomic profiling has found its application in screening extracts of macroorganisms as well as in the isolation and cultivation of suspected microbial producers of bioactive natural products.Metabolomics is being applied to identify and biotechnologically optimize the production of pharmacologically active secondary metabolites. The links between metabolome evolution during optimization and processing factors can be identified through metabolomics. Information obtained from a metabolomics dataset can efficiently establish cultivation and production processes at a small scale which will be finally scaled up to a fermenter system, while maintaining or enhancing synthesis of the desired compounds. MZmine (BMC Bioinformatics 11:395-399, 2010; http://mzmine.sourceforge.net/download.shtml ) and SIEVE ( http://www.vastscientific.com/resources/index.html ; Rapid Commun Mass Spectrom 22:1912-1918, 2008) softwares are utilized to perform differential analysis of sample populations to find significant expressed features of complex biomarkers between parameter variables. Metabolomes are identified with the aid of existing high resolution MS and NMR

  4. Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold.

    Science.gov (United States)

    Avilés, Edward; Prudhomme, Jacques; Le Roch, Karine G; Franzblau, Scott G; Chandrasena, Kevin; Mayer, Alejandro M S; Rodríguez, Abimael D

    2015-11-15

    A mixture-based combinatorial library of five Ugi adducts (4-8) incorporating known antitubercular and antimalarial pharmacophores was successfully synthesized, starting from the naturally occurring diisocyanide 3, via parallel Ugi four-center three-component reactions (U-4C-3CR). The novel α-acylamino amides obtained were evaluated for their antiinfective potential against laboratory strains of Mycobacterium tuberculosis H37Rv and chloroquine-susceptible 3D7 Plasmodium falciparum. Interestingly, compounds 4-8 displayed potent in vitro antiparasitic activity with higher cytotoxicity in comparison to their diisocyanide precursor 3, with the best compound exhibiting an IC50 value of 3.6 nM. Additionally, these natural product inspired hybrids potently inhibited in vitro thromboxane B2 (TXB2) and superoxide anion (O2(-)) generation from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity.

  5. Novel FeII and CoII Complexes of Natural Product Tryptanthrin: Synthesis and Binding with G-Quadruplex DNA

    Science.gov (United States)

    Zhong, Yi-ning; Zhang, Yan; Gu, Yun-qiong; Wu, Shi-yun; Shen, Wen-ying

    2016-01-01

    Tryptanthrin is one of the most important members of indoloquinoline alkaloids. We obtained this alkaloid from Isatis. Two novel FeII and CoII complexes of tryptanthrin were first synthesized. Single-crystal X-ray diffraction analyses show that these complexes display distorted four-coordinated tetrahedron geometry via two heterocyclic nitrogen and oxygen atoms from tryptanthrin ligand. Binding with G-quadruplex DNA properties revealed that both complexes were found to exhibit significant interaction with G-quadruplex DNA. This study may potentially serve as the basis of future rational design of metal-based drugs from natural products that target the G-quadruplex DNA. PMID:27698647

  6. Plant cell culture strategies for the production of natural products.

    Science.gov (United States)

    Ochoa-Villarreal, Marisol; Howat, Susan; Hong, SunMi; Jang, Mi Ok; Jin, Young-Woo; Lee, Eun-Kyong; Loake, Gary J

    2016-03-01

    Plants have evolved a vast chemical cornucopia to support their sessile lifestyles. Man has exploited this natural resource since Neolithic times and currently plant-derived chemicals are exploited for a myriad of applications. However, plant sources of most high-value natural products (NPs) are not domesticated and therefore their production cannot be undertaken on an agricultural scale. Further, these plant species are often slow growing, their populations limiting, the concentration of the target molecule highly variable and routinely present at extremely low concentrations. Plant cell and organ culture constitutes a sustainable, controllable and environmentally friendly tool for the industrial production of plant NPs. Further, advances in cell line selection, biotransformation, product secretion, cell permeabilisation, extraction and scale-up, among others, are driving increases in plant NP yields. However, there remain significant obstacles to the commercial synthesis of high-value chemicals from these sources. The relatively recent isolation, culturing and characterisation of cambial meristematic cells (CMCs), provides an emerging platform to circumvent many of these potential difficulties. [BMB Reports 2016; 49(3): 149-158].

  7. Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

    Directory of Open Access Journals (Sweden)

    Helena M. C. Ferraz

    2008-01-01

    Full Text Available The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

  8. Natural and engineered biosynthesis of fluorinated natural products.

    Science.gov (United States)

    Walker, Mark C; Chang, Michelle C Y

    2014-09-21

    Both natural products and synthetic organofluorines play important roles in the discovery and design of pharmaceuticals. The combination of these two classes of molecules has the potential to be useful in the ongoing search for new bioactive compounds but our ability to produce site-selectively fluorinated natural products remains limited by challenges in compatibility between their high structural complexity and current methods for fluorination. Living systems provide an alternative route to chemical fluorination and could enable the production of organofluorine natural products through synthetic biology approaches. While the identification of biogenic organofluorines has been limited, the study of the native organisms and enzymes that utilize these compounds can help to guide efforts to engineer the incorporation of this unusual element into complex pharmacologically active natural products. This review covers recent advances in understanding both natural and engineered production of organofluorine natural products.

  9. Fungi as a source of natural coumarins production.

    Science.gov (United States)

    Costa, Tania Maria; Tavares, Lorena Benathar Ballod; de Oliveira, Débora

    2016-08-01

    Natural coumarins and derivatives are compounds that occur naturally in several organisms (plant, bacteria, and fungi) consisting of fused benzene and α-pyrone rings. These compounds show high technological potential applications in agrochemical, food, pharmaceuticals, and cosmetics industries. Therefore, the need for bulk production of coumarins and the advancement of the chemical and pharmaceutical industries led to the development of synthetic coumarin. However, biotransformation process, synthetic bioengineering, metabolic engineering, and bioinformatics have proven effective in the production of natural products. Today, these biological systems are recognized as green chemistry innovation and business strategy. This review article aims to report the potential of fungi for synthesis of coumarin. These microorganisms are described as a source of natural products capable of synthesizing many bioactive metabolites. The features, classification, properties, and industrial applications of natural coumarins as well as new molecules obtained by basidiomycetes and ascomycetes fungi are reported in order to explore a topic not yet discussed in the scientific literature.

  10. Hot springs and cool natural products.

    Science.gov (United States)

    Kwon, Ho Jeong; Lee, Choong Hwan; Osada, Hiroyuki; Yoshida, Minoru; Imoto, Masaya

    2008-08-01

    Natural products have played a unique role in providing new tools and insights in chemical biology. The tremendous value of natural products was highlighted by scientists from Korea and Japan at the 4(th) Korea-Japan Chemical Biology symposium.

  11. Nigerian Journal of Natural Products and Medicine

    African Journals Online (AJOL)

    Nigerian Journal of Natural Products and Medicine. ... 1982 dedicated to the promotion of Pharmacognosy, Natural Products and Traditional Medicine. .... Acuminatoside: a new anticancer compound from the maiden breast plant · EMAIL FULL ...

  12. Teaching 'natural product chemistry' in Tanzania | Buchanan ...

    African Journals Online (AJOL)

    Teaching 'natural product chemistry' in Tanzania. ... PROMOTING ACCESS TO AFRICAN RESEARCH. AFRICAN JOURNALS ONLINE (AJOL) · Journals ... Natural products 'historically' and 'today' have vast importance. This article describes ...

  13. Synthesis and anticancer activity of silver(I)-N-heterocyclic carbene complexes derived from the natural xanthine products caffeine, theophylline and theobromine.

    Science.gov (United States)

    Mohamed, Heba A; Lake, Benjamin R M; Laing, Thomas; Phillips, Roger M; Willans, Charlotte E

    2015-04-28

    A new library of silver(I)-N-heterocyclic carbene complexes prepared from the natural products caffeine, theophylline and theobromine is reported. The complexes have been fully characterised using a combination of NMR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction analysis. Furthermore, the hydrophobicity of the complexes has been measured. The silver(I)-N-heterocyclic carbenes have been evaluated for their antiproliferative properties against a range of cancer cell lines of different histological types, and compared to cisplatin. The data shows different profiles of response when compared to cisplatin in the same panel of cells, indicating a different mechanism of action. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity delivering higher cytotoxicity.

  14. 生物活性天然产物羽扇豆醇肉桂酸酯的合成%Synthesis of Lupeol Cinnamate as Bioactive Natural Product

    Institute of Scientific and Technical Information of China (English)

    李伟杰

    2012-01-01

    以DCC作缩合剂、DMAP作催化剂,羽扇豆醇和肉桂酸在二氯甲烷中室温反应24 h合成了生物活性天然产物羽扇豆醇肉桂酸酯,收率为86.5%。产物的结构经1H NMR和ESI-MS确证。%Lupeol reacted with cinnamic acid for 24 h in dichloromethane at ambient temperature to afford lupeol cinnamate as bioactive natural product in the yield of 86.5 % in the presence of DCC as dehydrating agent and DMAP as catalyst.Its chemical structure was determined by 1H NMR and ESI-MS spectra.

  15. Natural products-based insecticidal agents 11. Synthesis and insecticidal activity of novel 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxin derivatives against Mythimna separata Walker in vivo.

    Science.gov (United States)

    Xu, Hui; Zhang, Jun-Liang

    2011-09-15

    In continuation of our program aimed at the discovery and development of natural products-based insecticidal agents, 14 novel 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxin derivatives were stereoselectively semisynthesized from podophyllotoxin, and preliminarily evaluated for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo. Especially compounds 9c' and 9g' exhibited the most promising and pronounced insecticidal activity than toosendanin, a commercial insecticide derived from Melia azedarach at 1mg/mL. Generally, it was preliminarily demonstrated that arylsulfonyloxy groups at the C-2 position of benzyloxy moiety and the length of the side chain on the benzenesulfonyloxy group of 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxins might be important for the insecticidal activity.

  16. Synthesis of Two Natural Oleanolic Acid Saponins

    Institute of Scientific and Technical Information of China (English)

    LI, Chun-Xia; ZANG, Jing; WANG, Peng; ZHANG, Xiu-Li; GUAN, Hua-Shi; LI, Ying-Xia

    2006-01-01

    Ocean University of China, Qingdao, Shandong 266003, China3-O-[β-D-Glucopyranosyl-(1→3)-α-L-arabinopyranosyl]-oleanolic acid-28-O-[β-D-glucopyranosyl] ester 1 was synthesized concisely by a convergent strategy. Using stepwise fashion for the synthesis of saponin 2,3-O-{ [β-D-glucopyranosyl-( 1→ 2 ) ]-[ α-L-arabinopyranosyl-( 1→ 3 ) ]-α-L-arabinopyranosyl }-oleanolic acid-28-O-(β-D-glucopyranosyl) ester, an abnormal phenomenon, that the terminal arabinosyl residue took the 1C4 conformation instead of typical 4C1 form, was observed. Deprotection or heating could not resume the normal conformation,which resulted in the product of 2' not 2.

  17. Synthesis of Natural and Unnatural Cyclooligomeric Depsipeptides Enabled by Flow Chemistry.

    Science.gov (United States)

    Lücke, Daniel; Dalton, Toryn; Ley, Steven V; Wilson, Zoe E

    2016-03-14

    Flow chemistry has been successfully integrated into the synthesis of a series of cyclooligomeric depsipeptides of three different ring sizes including the natural products beauvericin (1 a), bassianolide (2 b) and enniatin C (1 b). A reliable flow chemistry protocol was established for the coupling and macrocyclisation to form challenging N-methylated amides. This flexible approach has allowed the rapid synthesis of both natural and unnatural depsipeptides in high yields, enabling further exploration of their promising biological activity.

  18. Misassigned natural products and their revised structures.

    Science.gov (United States)

    Yoo, Hye-Dong; Nam, Sang-Jip; Chin, Young-Won; Kim, Min-Sun

    2016-02-01

    Natural products are a major pipeline for drug development and are responsible for more than 50 % of drugs on the market. NMR is a fundamental and powerful tool for the structure determination of natural products. It is essential to provide unambiguous chemical structure information on natural products in drug development research, including the structure-activity relationship, derivatization and pharmacokinetic/pharmacodynamic studies. Advancement of NMR instruments has made it possible to deal with nanomole-scale natural products for structure elucidation, but misinterpretation of NMR spectra still occurs. We review 21 natural products with revised chemical structures and the methods used for those revisions.

  19. In silico Design of "Un-Natural" Natural Products

    Directory of Open Access Journals (Sweden)

    Zucko; J. ...(et al.

    2008-05-01

    ClustScan, which are under development to model these processes in silico. The heart of CompGen is a specially structured database, based on BioSQL v1.29, which connects the biosynthetic order of synthase/synthetase enzymes to the sequences of the component polypeptides. The additional linkage to the gene sequences allows the integration of DNA sequence with product structure. The database contains sequences of the well-characterised PKS/NRPS clusters, and non-annotated sequenced clusters whose structure and functionis yet unknown, to act as building blocks for the production of novel products. It is easy to add custom sequences to the database and to annotate them by the use of propriety protein profiles designed by Pfam database and HMMER. One function of the program is the ability to generate virtual recombinants between clusters. This can be done using a recombination model (with optional parameters to predict sites for homologous recombination or by user defined recombination sites (e.g. to model in vitro genetic manipulation such as module replacement. The program predicts the linear polyketide structure of the resulting "un-natural" natural products with a chemical description using isomeric SMILES. Molecular modelling of the subsequent spontaneous cyclisation process produces structures for a virtual compound database for further molecular modelling studies using PASS and CDD technology. An optional "reverse genetics" module analyses a given chemical structure to see if it could be produced by a novel PKS/NRPS synthesis cluster and suggests the DNA sequence of a suitable cluster based on building blocks derived from clusters contained in the database.Overall, the CompGen allows in silico generation of the database of novel "un-natural" natural chemical compounds that can be used for in silico screening using PASS or CDD technology. The other integral generic program package, ClustScan, will recognise and annotate new gene clusters from microbial genome

  20. Studies on chemical structure modification and biology of a natural product, gambogic acid (I): Synthesis and biological evaluation of oxidized analogues of gambogic acid.

    Science.gov (United States)

    Wang, Jinxin; Zhao, Li; Hu, Yang; Guo, Qinglong; Zhang, Lei; Wang, Xiaojian; Li, Nianguang; You, Qidong

    2009-06-01

    Gambogic acid (GA), a natural product, exhibits high potency in inhibiting cancer cell growth through the effective induction of apoptosis. In order to investigate the structure-activity relationships of GA derivatives, 11 oxidized derivatives of GA were synthesized. Some of them showed strong inhibitory effects on HT-29, Bel-7402, BGC-823, A549, and SKOV 3 cell lines. Moreover, in this paper the cellular growth inhibitor 39-hydroxy-6-methoxy-gambogic acid methyl ester (10) was identified as a HepG2 cell apoptosis inhibitor through Annexin-V/PI double staining assay and the expression of the related apoptotic proteins (Bax and Bcl-2). Compound 10 may serve as a potential lead compound for the development of new anticancer drugs. Further SAR studies of GA derivatives indicated that modification of carbon-carbon double bond at C-32/33 or C-37/38 and of the methyl groups at C-39/C-35 can improve antitumor activity.

  1. Synthesis and antibacterial activity of sulfonamide derivatives at C-8 alkyl chain of anacardic acid mixture isolated from a natural product cashew nut shell liquid (CNSL)

    Indian Academy of Sciences (India)

    N Subhakara Reddy; A Srinivas Rao; M Adharvana Chari; V Ravi Kumar; V Jyothy; V Himabindu

    2012-05-01

    Synthesis and antibacterial activity of some novel biologically active sulfonamide derivatives at C-8 alkyl chain of anacardic acid (7a-7l), prepared from commercially available anacardic acid mixture (1a-d). These compounds were tested for Gram positive and Gram negative bacterial cultures; most of the compounds showed higher antibacterial activity compared with standard drug ampicillin.

  2. Natural products and body weight control

    Directory of Open Access Journals (Sweden)

    Jay Lee

    2011-01-01

    Full Text Available The purpose of the review was to summarise the effect of some commonly available natural products used for body weight management. We collected data from PubMed and scientific journals. There are numerous publications on this topic, however we have summarized the most commonly available and potent natural products from recent 53 publications. The natural products analyzed in this paper include catechins, capsaicin, conjugated linoleic acid, fucoxanthin, soy isoflavone, glabridin, astaxanthin and cyaniding-3-glucoside. These natural products are effective and safe for body weight management. Further studies need to be conducted to investigate the mechanism of action, metabolism, long term safety and side effects of these natural products, as well as interactions between these natural products with dietary components.

  3. Iridium-Catalyzed Dynamic Kinetic Isomerization: Expedient Synthesis of Carbohydrates from Achmatowicz Rearrangement Products.

    Science.gov (United States)

    Wang, Hao-Yuan; Yang, Ka; Bennett, Scott R; Guo, Sheng-rong; Tang, Weiping

    2015-07-20

    A highly stereoselective dynamic kinetic isomerization of Achmatowicz rearrangement products was discovered. This new internal redox isomerization provided ready access to key intermediates for the enantio- and diastereoselective synthesis of a series of naturally occurring sugars. The nature of the de novo synthesis also enables the preparation of both enantiomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Accounting Of Products Collected From Nature

    Directory of Open Access Journals (Sweden)

    Ahmet Gökgöz

    2015-12-01

    Full Text Available Products from nature can be classified as “production” or “collection from nature” within agricultural production. Products collected from nature vary in type and can sum up to important quantities. Thyme, mushroom, chestnut, sage, linden, saffron from plant origin can be given as examples to products from nature as well as fish, mussel, octopus, birds from animal origin. This study covers the accounting area of products obtained from nature. The evaluation of collection of these products from nature in terms of agricultural operation poses great importance for accounting issues. Thus, special care will be given to issues of accounting of these products within the scope of Turkish Tax Legislation and Turkish Accounting Standards

  5. Biosynthesis of natural products containing β-amino acids.

    Science.gov (United States)

    Kudo, Fumitaka; Miyanaga, Akimasa; Eguchi, Tadashi

    2014-08-01

    Covering: up to January, 2014. We focus here on β-amino acids as components of complex natural products because the presence of β-amino acids produces structural diversity in natural products and provides characteristic architectures beyond those of ordinary α-L-amino acids, thus generating significant and unique biological functions in nature. In this review, we first survey the known bioactive β-amino acid-containing natural products including nonribosomal peptides, macrolactam polyketides, and nucleoside-β-amino acid hybrids. Next, the biosynthetic enzymes that form β-amino acids from α-amino acids and the de novo synthesis of β-amino acids are summarized. Then, the mechanisms of β-amino acid incorporation into natural products are reviewed. Because it is anticipated that the rational swapping of the β-amino acid moieties with various side chains and stereochemistries by biosynthetic engineering should lead to the creation of novel architectures and bioactive compounds, the accumulation of knowledge regarding β-amino acid-containing natural product biosynthetic machinery could have a significant impact in this field. In addition, genome mining of characteristic β-amino acid biosynthetic genes and unique β-amino acid incorporation machinery could lead to the discovery of new β-amino acid-containing natural products.

  6. Marine Natural Products as Models to Circumvent Multidrug Resistance.

    Science.gov (United States)

    Long, Solida; Sousa, Emília; Kijjoa, Anake; Pinto, Madalena M M

    2016-07-08

    Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

  7. Counting on natural products for drug design

    Science.gov (United States)

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  8. The C7N aminocyclitol family of natural products.

    Science.gov (United States)

    Mahmud, Taifo

    2003-02-01

    This review covers microbial secondary metabolites classified in the family of C7N aminocyclitols, a relatively new class of natural products that is increasingly gaining recognition due to their significant biomedical and agricultural uses. Their discovery and structure determinations, their biosynthetic origin, biological properties, chemical synthesis, as well as their further development for pharmaceutical uses are described. The literature from 1970 to July 2002 is reviewed, with 269 references cited.

  9. Natural Connections on Riemannian Product Manifolds

    OpenAIRE

    Gribacheva, Dobrinka

    2011-01-01

    A Riemannian almost product manifold with integrable almost product structure is called a Riemannian product manifold. In the present paper the natural connections on such manifolds are studied, i.e. the linear connections preserving the almost product structure and the Riemannian metric.

  10. Food production and nature conservation

    NARCIS (Netherlands)

    Gordon, Iain J.; Squire, Geoff R.; Prins, Herbert H.T.

    2016-01-01

    Feeding the world's growing human population is increasingly challenging, especially as more people adopt a western diet and lifestyle. Doing so without causing damage to nature poses an even greater challenge. This book argues that in order to create a sustainable food supply whilst conserving

  11. Studies on chemical modification and biology of a natural product, gambogic acid (II): Synthesis and bioevaluation of gambogellic acid and its derivatives from gambogic acid as antitumor agents.

    Science.gov (United States)

    Wang, Jinxin; Ma, Junhai; You, Qidong; Zhao, Li; Wang, Fan; Li, Chong; Guo, Qinglong

    2010-09-01

    Gambogic acid (GA) has been reported to be a potent apoptosis inducer. The fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. We firstly reported the synthesis of gambogellic acid, which was generated under acid catalysis from readily available GA by a base-catalyzed diene intramolecular annelation. Sequentially, thirteen new compounds were synthesized and their inhibitory activity on HT-29, Bel-7402, BGC-823, and A549 cell lines were evaluated in vitro by MTT assay, and (38, 40)-epoxy-33-chlorogambogellic acid (4) was identified as a BGC-823 cell apoptosis inducer through MTT cell assay, observations of morphological changes, and Annexin-V/PI double-staining assay. Compound 4 showed significant effects in inducing apoptosis and might serve as a potential lead compound for discovery of new anticancer drugs. Further structure-activity relationships (SARs) of gambogic acid derivatives were discussed.

  12. Cyclic Sulfamidate Enabled Syntheses of Amino Acids, Peptides, Carbohydrates, and Natural Products

    Science.gov (United States)

    This article reviews the emergence of cyclic sulfamidates as versatile intermediatesfor the synthesis of unnatural amino acids, chalcogen peptides, modified sugars, drugs and drug candidates, and important natural products.

  13. Cyclic Sulfamidate Enabled Syntheses of Amino Acids, Peptides, Carbohydrates, and Natural Products

    Science.gov (United States)

    This article reviews the emergence of cyclic sulfamidates as versatile intermediatesfor the synthesis of unnatural amino acids, chalcogen peptides, modified sugars, drugs and drug candidates, and important natural products.

  14. Functional chromatographic technique for natural product isolation†

    Science.gov (United States)

    Lau, Eric C.; Mason, Damian J.; Eichhorst, Nicole; Engelder, Pearce; Mesa, Celestina; Kithsiri Wijeratne, E. M.; Gunaherath, G. M. Kamal B.; Leslie Gunatilaka, A. A.

    2015-01-01

    Natural product discovery arises through a unique interplay between chromatographic purification and biological assays. Currently, most techniques used for natural product purification deliver leads without a defined biological action. We now describe a technique, referred to herein as functional chromatography, that deploys biological affinity as the matrix for compound isolation. PMID:25588099

  15. Functional chromatographic technique for natural product isolation†

    OpenAIRE

    Lau, Eric C.; Mason, Damian J.; Eichhorst, Nicole; Engelder, Pearce; Mesa, Celestina; Kithsiri Wijeratne, E. M.; Gunaherath, G. M. Kamal B.; Leslie Gunatilaka, A. A.; La Clair, James J.; Chapman, Eli

    2015-01-01

    Natural product discovery arises through a unique interplay between chromatographic purification and biological assays. Currently, most techniques used for natural product purification deliver leads without a defined biological action. We now describe a technique, referred to herein as functional chromatography, that deploys biological affinity as the matrix for compound isolation.

  16. Natural product-based design, synthesis and biological evaluation of anthra[2,1-d]thiazole-6,11-dione derivatives from rhein as novel antitumour agents.

    Science.gov (United States)

    Liang, Yu-Kun; Yue, Zhi-Zhou; Li, Jia-Xin; Tan, Cun; Miao, Ze-Hong; Tan, Wen-Fu; Yang, Chun-Hao

    2014-09-12

    Two series of novel 2-substituted 5,7-dihydroxyanthra[2,1-d]thiazole-6,11-dione derivatives from natural rhein were designed, synthesized and evaluated for their antitumour activities against human cancer cell lines A549 and HeLa in vitro.

  17. Bioactive natural products from novel microbial sources.

    Science.gov (United States)

    Challinor, Victoria L; Bode, Helge B

    2015-09-01

    Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics.

  18. Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2016-09-01

    Full Text Available Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1–2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin, respectively.

  19. Targeting Nuclear Receptors with Marine Natural Products

    Directory of Open Access Journals (Sweden)

    Chunyan Yang

    2014-01-01

    Full Text Available Nuclear receptors (NRs are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators.

  20. Natural food pigments application in food products

    Directory of Open Access Journals (Sweden)

    Emilia Janiszewska-Turak

    2016-12-01

    Full Text Available Natural pigments, food compounds, are responsible for the colour of the products. These additives can impart, to deepen or renew the colour of the product, if it has been lost while processing. They also improve the taste of the product and facilitate its identification. It is hard to imagine today’s food industry without the use of pigments. Presently, more and more conscious con­sumers are demanding products to be coloured with natural pigments or any pigment added to the final product. Artificial pigments are considered to be harmful and undesirable so food manufacturers focus on the use of natural colour substances. 16 natural pigments are presently permitted to be used. These compounds are: betalains – betanin, quinones – cochineal, flavonoids – anthocyan­ins, isoprenoids – carotene, annatto (bixin, norbixin, paprika extract, lutein, canthaxanthin, porphyrins – chlorophylls and chlorophyllins and copper complexes of these compounds, and others: caramels, curcumin, or plant coal.

  1. Engineering microbial factories for synthesis of value-added products.

    Science.gov (United States)

    Du, Jing; Shao, Zengyi; Zhao, Huimin

    2011-08-01

    Microorganisms have become an increasingly important platform for the production of drugs, chemicals, and biofuels from renewable resources. Advances in protein engineering, metabolic engineering, and synthetic biology enable redesigning microbial cellular networks and fine-tuning physiological capabilities, thus generating industrially viable strains for the production of natural and unnatural value-added compounds. In this review, we describe the recent progress on engineering microbial factories for synthesis of valued-added products including alkaloids, terpenoids, flavonoids, polyketides, non-ribosomal peptides, biofuels, and chemicals. Related topics on lignocellulose degradation, sugar utilization, and microbial tolerance improvement will also be discussed.

  2. "Pruning of biomolecules and natural products (PBNP)": an innovative paradigm in drug discovery.

    Science.gov (United States)

    Bathula, Surendar Reddy; Akondi, Srirama Murthy; Mainkar, Prathama S; Chandrasekhar, Srivari

    2015-06-21

    The source or inspiration of many marketed drugs can be traced back to natural product research. However, the chemical structure of natural products covers a wide spectrum from very simple to complex. With more complex structures it is often desirable to simplify the molecule whilst retaining the desired biological activity. This approach seeks to identify the structural unit or pharmacophore responsible for the desired activity. Such pharmacophores have been the start point for a wide range of lead generation and optimisation programmes using techniques such as Biology Oriented Synthesis, Diversity Oriented Synthesis, Diverted Total Synthesis, and Fragment Based Drug Discovery. This review discusses the literature precedence of simplification strategies in four areas of natural product research: proteins, polysaccharides, nucleic acids, and compounds isolated from natural product extracts, and their impact on identifying therapeutic products.

  3. Marine Natural Products as Lead Compound for New Drug Discovery

    Institute of Scientific and Technical Information of China (English)

    JIANG; Biao

    2001-01-01

    The study of natural product has long been motivated by a quest for some benefit to man, the discover. Recent years have witnessed growing attention to the isolation, identification and synthesis of the marine natural. Although marine organisms do not have a long history of medicine applications like terrestrial plants, some marine organisms have left an extensive record of hazard to mankind. The isolation and identification of saxtoxin, tetradotoxin and lyngbyatoxin resulted from such reported. The marine biosphere has long held great promise as source of anticancer compounds, while a number of screening efforts has indicated a much higher percentage of antineplastic and antitumor activity than terrestrial plants. Several marine natural products have made their appearance in clinical trials at the National Cancer Institute, such as the didemnis, , bryostatins, This finds marine invertebratehave reinvigorated interest and effort in anticancer agent from marine invertebrate.  ……

  4. Marine Natural Products as Lead Compound for New Drug Discovery

    Institute of Scientific and Technical Information of China (English)

    JIANG Biao

    2001-01-01

    @@ The study of natural product has long been motivated by a quest for some benefit to man, the discover. Recent years have witnessed growing attention to the isolation, identification and synthesis of the marine natural. Although marine organisms do not have a long history of medicine applications like terrestrial plants, some marine organisms have left an extensive record of hazard to mankind. The isolation and identification of saxtoxin, tetradotoxin and lyngbyatoxin resulted from such reported. The marine biosphere has long held great promise as source of anticancer compounds, while a number of screening efforts has indicated a much higher percentage of antineplastic and antitumor activity than terrestrial plants. Several marine natural products have made their appearance in clinical trials at the National Cancer Institute, such as the didemnis, , bryostatins, This finds marine invertebratehave reinvigorated interest and effort in anticancer agent from marine invertebrate.

  5. Property Based Process and Product Synthesis and Design

    DEFF Research Database (Denmark)

    Eden, Mario Richard

    2003-01-01

    This thesis describes the development of a general framework for solving process and product design problems. Targeting the desired performance of the system in a systematic manner relieves the iterative nature of conventional design techniques. Furthermore, conventional component based methods...... roles a property model plays at different stages of the solution to a design problem, it is discovered that by decoupling the constitutive equations, that make up the property model, from the balance and constraint equations of the process or product model, a significant reduction in problem complexity...... in terms of the constitutive (synthesis/design) variables instead of the process variables, thus providing the synthesis/design targets. The second reverse problem (reverse property prediction) solves the constitutive equations to identify unit operations, operating conditions and/or products by matching...

  6. Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale.

    Science.gov (United States)

    Deprés, Jean-Pierre; Delair, Philippe; Poisson, Jean-François; Kanazawa, Alice; Greene, Andrew E

    2016-02-16

    11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades' worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural γ-butyrolactones (e.g., β-oxygenated γ-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring γ-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O-(mesitylenesulfonyl)hydroxylamine (Tamura's reagent). These 5-membered carbocycles, γ-butyrolactones, and γ-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this "three-atom olefin annelation" approach. In addition

  7. Cancer wars: natural products strike back

    Science.gov (United States)

    Basmadjian, Christine; Zhao, Qian; Bentouhami, Embarek; Djehal, Amel; Nebigil, Canan G.; Johnson, Roger A.; Serova, Maria; de Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent G.

    2014-01-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90's they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many solid tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, 12 novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery. PMID:24822174

  8. Sources for Leads: Natural Products and Libraries.

    Science.gov (United States)

    van Herwerden, Eric F; Süssmuth, Roderich D

    2016-01-01

    Natural products have traditionally been a major source of leads in the drug discovery process. However, the development of high-throughput screening led to an increased interest in synthetic methods that enabled the rapid construction of large libraries of molecules. This resulted in the termination or downscaling of many natural product research programs, but the chemical libraries did not necessarily produce a larger amount of drug leads. On one hand, this chapter explores the current state of natural product research within the drug discovery process. On the other hand it evaluates the efforts made to increase the amount of leads generated from chemical libraries and considers what role natural products could play here.

  9. Cancer wars: Natural products strike back

    Science.gov (United States)

    Basmadjian, Christine; Zhao, Qian; Djehal, Amel; Bentouhami, Embarek; Nebigil, Canan; Johnson, Roger; Serova, Maria; De Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent

    2014-05-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90’s they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many sol¬¬id tumors, which revitalized the interest in natural products. With the approval of rapamycin in 2007, twelve novel natural product derivatives have been brought to market. The present review describes the discovery and development of these new anticancer drugs and highlights the peculiarities of natural product and new trends in this exciting field of drug discovery.

  10. ARTEMISININ: THE JOURNEY FROM NATURAL PRODUCT TO ...

    African Journals Online (AJOL)

    services, many parents lose their children to complications ... ARTEMISININ: THE JOURNEY FROM NATURAL PRODUCT TO NOBEL PRIZE. SUMMARY ... Medicine, where she has remained for over 55 years. After joining ... An advantage of.

  11. High impact technologies for natural products screening.

    Science.gov (United States)

    Koehn, Frank E

    2008-01-01

    Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library

  12. Cancer wars: Natural products strike back

    OpenAIRE

    Christine eBasmadjian; Qian eZhao; Amel eDjehal; Embarek eBentouhami; Nebigil, Canan G.; Johnson, Roger A.; Maria eSerova; Armand eDe Gramont; Sandrine eFaivre; Eric eRaymond; Désaubry, Laurent G.

    2014-01-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90’s they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many sol¬¬id tumors, which revitalized the interest in natural products. With the approval of ...

  13. Cancer wars: natural products strike back

    OpenAIRE

    Basmadjian, Christine; Zhao, Qian; Bentouhami, Embarek; Djehal, Amel; Nebigil, Canan G.; Johnson, Roger A.; Serova, Maria; Gramont, Armand de; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent G.

    2014-01-01

    Natural products have historically been a mainstay source of anticancer drugs, but in the 90's they fell out of favor in pharmaceutical companies with the emergence of targeted therapies, which rely on antibodies or small synthetic molecules identified by high throughput screening. Although targeted therapies greatly improved the treatment of a few cancers, the benefit has remained disappointing for many solid tumors, which revitalized the interest in natural products. With the approval of ra...

  14. Reconstructing fungal natural product biosynthetic pathways.

    Science.gov (United States)

    Lazarus, C M; Williams, K; Bailey, A M

    2014-10-01

    Large scale fungal genome sequencing has revealed a multitude of potential natural product biosynthetic pathways that remain uncharted. Here we describe some of the methods that have been used to explore them via heterologous gene expression. We focus on filamentous fungal hosts and discuss the technological challenges and successes behind the reconstruction of fungal natural product pathways. Optimised, efficient heterologous expression of reconstructed biosynthetic pathways promises progress in the discovery of novel compounds that could be utilised by the pharmaceutical and agrochemical industries.

  15. Natural Mineral-marine Manganese Nodule as a Novel Catalyst for the Synthesis of Carbon Nanotubes

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Multi-walled carbon nanotubes were fabricated by the pyrolysis of acetylene with naturally occurring marine manganese nodules as a novel catalyst at an elevated temperature.The nanotube product was examined by transmission electron microscopy.The method is expected to be the simplest one to synthesize carbon nanotubes due to unnecessary synthesis of catalyst.

  16. TEACHING 'NATURAL PRODUCT CHEMISTRY' IN TANZANIA

    African Journals Online (AJOL)

    Temechegn

    natural product chemistry or chemistry of natural medicines [4]. There is even ... The course is an optional course (not core) open to 3rd year (final year) students in the. Faculty of .... a gift to the newborn Jesus (Matthew 2:11) [24]. • Olive oil is ...

  17. Technical note: Hapten synthesis, antibody production and development of an enzyme-linked immunosorbent assay for detection of the natural steroidal alkaloid Dendrogenin A.

    Science.gov (United States)

    de Medina, Philippe; Paillasse, Michael R; Segala, Gregory; Al Saati, Talal; Boyes, Jeannine; Delsol, Georges; Allal, Cuider; Marsili, Sabrina; Silvente-Poirot, Sandrine; Poirot, Marc

    2013-03-01

    We have recently discovered the existence of 5α-Hydroxy-6β-[2-(1H-imidazol-4-yl)ethylamino]cholestan-3β-ol, called Dendrogenin A (DDA), as the first endogenous steroidal alkaloid ever described in mammals. We found that the DDA content of tumors and cancer cell lines was low or absent compared with normal cells showing that a deregulation in DDA biosynthesis was associated with cancer and therefore suggesting that DDA could represent a metabolomic cancer biomarker. This prompted us to produce antibodies that selectively recognize DDA. For this purpose, the hapten 5α-hydroxy-6β-[2-(1H-imidazol-4-yl)ethylamino]cholestan-3β-o-hemisuccinate with a carboxylic spacer arm attached to the 3β-hydroxyl group of DDA was synthesized. The hapten was coupled to bovine serum albumin and keyhole limpet hemocyanin for antibody production to develop an enzyme-linked immunosorbent assay (ELISA). The protein conjugates were injected into BALB/c mice to raise antibodies. The monoclonal antibodies that were secreted from the hybridoma cell lines established were assessed with indirect ELISA by competitive assays using dilutions of a DDA standard. The antibodies from the selected hybridomas had an IC(50) value ranging from 0.8 to 425 ng/ml. Three antibodies showed no cross-reactivity with structurally related compounds including histamine, cholesterol, ring B oxysterols and a regio-isomer of DDA. In this study, high-affinity and selective antibodies against DDA were produced for the first time, and a competitive indirect ELISA was developed.

  18. Tailored fischer-tropsch synthesis product distribution

    Science.gov (United States)

    Wang, Yong [Richland, WA; Cao, Chunshe [Kennewick, WA; Li, Xiaohong Shari [Richland, WA; Elliott, Douglas C [Richland, WA

    2012-06-19

    Novel methods of Fischer-Tropsch synthesis are described. It has been discovered that conducting the Fischer-Tropsch synthesis over a catalyst with a catalytically active surface layer of 35 microns or less results in a liquid hydrocarbon product with a high ratio of C.sub.5-C.sub.20:C.sub.20+. Descriptions of novel Fischer-Tropsch catalysts and reactors are also provided. Novel hydrocarbon compositions with a high ratio of C.sub.5-C.sub.20:C.sub.20+ are also described.

  19. A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis.

    Science.gov (United States)

    Gao, Fang; Carr, James L; Hoveyda, Amir H

    2014-02-05

    A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

  20. Marine actinobacteria: an important source of bioactive natural products.

    Science.gov (United States)

    Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

    2014-07-01

    Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Studies on Atropo-Enantioselective Synthesis of the Natural Chiral Axial Biaryls

    Institute of Scientific and Technical Information of China (English)

    LIN Guo-Qiang

    2004-01-01

    Ary-aryl bond formation plays an important role in modem organic synthesis. These bonds are very of ten occurred in natural products such as alkaloids as well as in numerous biologically active parts of pharmaceutical and agrochemical specialties. In addition, they are also the scaffolds of some of the most efficient and selective ligands for asymmetric catalysts, especially when atropisomery is possible.In this report, we report the structure and the enantioselective synthesis of some natural occurring bioactive products. The focus will be Mainly in our recently discovered Ni(0) catalyzed homo-coupling and cross-coupling of aryl halide with coumarinyl mesylates and the enantioselective synthesis of phthalides in the presence of bidentated ligands with up to 99% e.e.

  2. Natural product discovery: past, present, and future.

    Science.gov (United States)

    Katz, Leonard; Baltz, Richard H

    2016-03-01

    Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

  3. Using Genomics for Natural Product Structure Elucidation.

    Science.gov (United States)

    Tietz, Jonathan I; Mitchell, Douglas A

    2016-01-01

    Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

  4. Synthesis of human-nature feedbacks

    Directory of Open Access Journals (Sweden)

    Vanessa Hull

    2015-09-01

    Full Text Available In today's globalized world, humans and nature are inextricably linked. The coupled human and natural systems (CHANS framework provides a lens with which to understand such complex interactions. One of the central components of the CHANS framework involves examining feedbacks among human and natural systems, which form when effects from one system on another system feed back to affect the first system. Despite developments in understanding feedbacks in single disciplines, interdisciplinary research on CHANS feedbacks to date is scant and often site-specific, a shortcoming that prevents complex coupled systems from being fully understood. The special feature "Exploring Feedbacks in Coupled Human and Natural Systems (CHANS" makes strides to fill this critical gap. Here, as an introduction to the special feature, we provide an overview of CHANS feedbacks. In addition, we synthesize key CHANS feedbacks that emerged in the papers of this special feature across agricultural, forest, and urban landscapes. We also examine emerging themes explored across the papers, including multilevel feedbacks, time lags, and surprises as a result of feedbacks. We conclude with recommendations for future research that can build upon the foundation provided in the special feature.

  5. Psychoactive natural products: overview of recent developments

    Directory of Open Access Journals (Sweden)

    István Ujváry

    2014-03-01

    Full Text Available Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural products are also mentioned.

  6. Psychoactive natural products: overview of recent developments.

    Science.gov (United States)

    Ujváry, István

    2014-01-01

    Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began to spread beyond their traditional geographical and cultural boundaries. The aim of the present paper is to briefly summarize recent findings on the psychopharmacology of the most prominent psychoactive natural products. Current knowledge on a few lesser-known drugs, including bufotenine, glaucine, kava, betel, pituri, lettuce opium and kanna is also reviewed. In addition, selected cases of alleged natural (or semi-natural) products are also mentioned.

  7. Review: Natural products from Genus Selaginella (Selaginellaceae

    Directory of Open Access Journals (Sweden)

    AHMAD DWI SETYAWAN

    2011-01-01

    Full Text Available Setyawan AD. 2011. Natural products from Genus Selaginella (Selaginellaceae. Nusantara Bioscience 3: 44-58. Selaginella is a potent medicinal-stuff, which contains diverse of natural products such as alkaloid, phenolic (flavonoid, and terpenoid. This species is traditionally used to cure several diseases especially for wound, after childbirth, and menstrual disorder. Biflavonoid, a dimeric form of flavonoids, is the most valuable natural products of Selaginella, which constituted at least 13 compounds, namely amentoflavone, 2',8''-biapigenin, delicaflavone, ginkgetin, heveaflavone, hinokiflavone, isocryptomerin, kayaflavone, ochnaflavone, podocarpusflavone A, robustaflavone, sumaflavone, and taiwaniaflavone. Ecologically, plants use biflavonoid to response environmental condition such as defense against pests, diseases, herbivory, and competitions; while human medically use biflavonoid especially for antioxidant, anti-inflammatory, and anti carcinogenic. Selaginella also contains valuable disaccharide, namely trehalose that has long been known for protecting from desiccation and allows surviving severe environmental stress. The compound has very prospects as molecular stabilizer in the industries based bioresources.

  8. Countercurrent Separation of Natural Products: An Update

    Science.gov (United States)

    2015-01-01

    This work assesses the current instrumentation, method development, and applications in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CCS). The article provides a critical review of the CCS literature from 2007 since our last review (J. Nat. Prod.2008, 71, 1489–1508), with a special emphasis on the applications of CCS in natural products research. The current state of CCS is reviewed in regard to three continuing topics (instrumentation, solvent system development, theory) and three new topics (optimization of parameters, workflow, bioactivity applications). The goals of this review are to deliver the necessary background with references for an up-to-date perspective of CCS, to point out its potential for the natural product scientist, and thereby to induce new applications in natural product chemistry, metabolome, and drug discovery research involving organisms from terrestrial and marine sources. PMID:26177360

  9. Early State Research on Antifungal Natural Products

    Directory of Open Access Journals (Sweden)

    Melyssa Negri

    2014-03-01

    Full Text Available Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates.

  10. Anti-Inflammatory Activity of Natural Products

    Directory of Open Access Journals (Sweden)

    Abdullatif Azab

    2016-10-01

    Full Text Available This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range of review and research articles that have reported on the anti-inflammatory effects of extracts and/or pure compounds derived from natural products. Moreover, this review pinpoints some interesting traditionally used medicinal plants that were not investigated yet.

  11. An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.

    Science.gov (United States)

    Johnston, Chad W; Skinnider, Michael A; Wyatt, Morgan A; Li, Xiang; Ranieri, Michael R M; Yang, Lian; Zechel, David L; Ma, Bin; Magarvey, Nathan A

    2015-09-28

    Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.

  12. Plants as natural antioxidants for meat products

    Science.gov (United States)

    Tomović, V.; Jokanović, M.; Šojić, B.; Škaljac, S.; Ivić, M.

    2017-09-01

    The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic ones. Plants materials provide good alternatives. Spices and herbs, generally used for their flavouring characteristics, can be added to meat products in various forms: whole, ground, or as isolates from their extracts. These natural antioxidants contain some active compounds, which exert antioxidative potential in meat products. This antioxidant activity is most often due to phenolic acids, phenolic diterpenes, flavonoids and volatile oils. Each of these compounds often has strong H-donating activity, thus making them extremely effective antioxidants; some compounds can chelate metals and donate H to oxygen radicals, thus slowing oxidation via two mechanisms. Numerous studies have demonstrated the efficacy of natural antioxidants when used in meat products. Based on this literature review, it can be concluded that natural antioxidants are added to fresh and processed meat and meat products to delay, retard, or prevent lipid oxidation, retard development of off-flavours (rancidity), improve colour stability, improve microbiological quality and extend shelf-life, without any damage to the sensory or nutritional properties.

  13. Chocolate: A Marvelous Natural Product of Chemistry

    Science.gov (United States)

    Tannenbaum, Ginger

    2004-01-01

    The study of chocolate, a natural product, can be beneficial for the chemistry students as they ask frequently about the relevancy of their chemistry classes. The history of chocolate, its chemical and physical changes during processing, its composition, different crystalline forms, tempering and its viscosity are discussed.

  14. Standardization for natural product synthetic biology

    NARCIS (Netherlands)

    Zhao, Huimin; Medema, Marnix H.

    2016-01-01

    Standardization is one of the foundational features of modern-day engineering, and the use of standardized parts and processes is a key element that distinguishes bona fide synthetic biology from traditional genetic engineering. Here, we discuss the role of standardization in natural product

  15. Marine natural products as prototype agrochemical agents.

    Science.gov (United States)

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A; Dunbar, D Charles; Perry, Tony L; Wilkins, Scott P; Hamann, Mark T; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A

    2003-04-09

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents.

  16. Marine Natural Products as Prototype Agrochemical Agents

    OpenAIRE

    Peng, Jiangnan; Shen, Xiaoyu; Khalid A. El Sayed; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2003-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents.

  17. Natural products – learning chemistry from plants

    NARCIS (Netherlands)

    Staniek, A.; Bouwmeester, H.J.; Fraser, P.D.; Kayser, O.; Martens, S.; Tissier, A.; Krol, van der A.R.; Wessjohann, L.; Warzecha, H.

    2014-01-01

    Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as

  18. Natural products – learning chemistry from plants

    NARCIS (Netherlands)

    Staniek, A.; Bouwmeester, H.J.; Fraser, P.D.; Kayser, O.; Martens, S.; Tissier, A.; Krol, van der A.R.; Wessjohann, L.; Warzecha, H.

    2014-01-01

    Plant natural products (PNPs) are unique in that they represent a vast array of different structural features, ranging from relatively simple molecules to very complex ones. Given the fact that many plant secondary metabolites exhibit profound biological activity, they are frequently used as fragran

  19. Natural products from microbes associated with insects

    DEFF Research Database (Denmark)

    Beemelmanns, Christine; Guo, Huijuan; Rischer, Maja;

    2016-01-01

    Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We...

  20. Computational approaches to natural product discovery

    NARCIS (Netherlands)

    Medema, M.H.; Fischbach, M.A.

    2015-01-01

    Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natura

  1. Hydrothermal synthesis of zeolites from natural stellerite

    Institute of Scientific and Technical Information of China (English)

    李酽; 汪信; 董元彩; 朱俊武

    2002-01-01

    Y and P zeolites were synthesized hydrothermally from natural stellerite under different conditions and were characterized via XRD and FT-IR.The results show that the higher crystallinity of Y zeolite can be obtained in hydrothermal system with low alkalinity,low Ca2+/Na+ ratio,and high SiO2/Al2O3 ratio.The lattice space of the samples decreases as crystallization time increases.P Zeolite is prompted under condition of higher alkalinity and higher Ca2+/Na+ ratio.The intensity and number of bands in the range of 400 cm-1~900 cm-1 increases with reaction time.Bands at 680 cm-1,760 cm-1 and 860 cm-1 corresponding to Y zeolite appear during the crystallization stage.Most of these bands shift to higher wavenumbers when SiO2/Al2O3 ratio increases generally.In the hydrothermal system with reverse condition above,bands at 600 cm-1,420 cm-1~470 cm-1 hardly change as the crystallization time increases and the main crystal phase of P zeolite is obtained.

  2. Natural products in modern life science.

    Science.gov (United States)

    Bohlin, Lars; Göransson, Ulf; Alsmark, Cecilia; Wedén, Christina; Backlund, Anders

    2010-06-01

    With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure-activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific

  3. [Status of libraries and databases for natural products at abroad].

    Science.gov (United States)

    Zhao, Li-Mei; Tan, Ning-Hua

    2015-01-01

    For natural products are one of the important sources for drug discovery, libraries and databases of natural products are significant for the development and research of natural products. At present, most of compound libraries at abroad are synthetic or combinatorial synthetic molecules, resulting to access natural products difficult; for information of natural products are scattered with different standards, it is difficult to construct convenient, comprehensive and large-scale databases for natural products. This paper reviewed the status of current accessing libraries and databases for natural products at abroad and provided some important information for the development of libraries and database for natural products.

  4. Contrast negation and texture synthesis differentially disrupt natural texture appearance.

    Science.gov (United States)

    Balas, Benjamin

    2012-01-01

    Natural textures have characteristic image statistics that make them discriminable from unnatural textures. For example, both contrast negation and texture synthesis alter the appearance of natural textures even though each manipulation preserves some features while disrupting others. Here, we examined the extent to which contrast negation and texture synthesis each introduce or remove critical perceptual features for discriminating unnatural textures from natural textures. We find that both manipulations remove information that observers use for distinguishing natural textures from transformed versions of the same patterns, but do so in different ways. Texture synthesis removes information that is relevant for discrimination in both abstract patterns and ecologically valid textures, and we also observe a category-dependent asymmetry for identifying an "oddball" real texture among synthetic distractors. Contrast negation exhibits no such asymmetry, and also does not impact discrimination performance in abstract patterns. We discuss our results in the context of the visual system's tuning to ecologically relevant patterns and other results describing sensitivity to higher-order statistics in texture patterns.

  5. NOVEL REACTOR FOR THE PRODUCTION OF SYNTHESIS GAS

    Energy Technology Data Exchange (ETDEWEB)

    Vasilis Papavassiliou; Leo Bonnell; Dion Vlachos

    2004-12-01

    Praxair investigated an advanced technology for producing synthesis gas from natural gas and oxygen This production process combined the use of a short-reaction time catalyst with Praxair's gas mixing technology to provide a novel reactor system. The program achieved all of the milestones contained in the development plan for Phase I. We were able to develop a reactor configuration that was able to operate at high pressures (up to 19atm). This new reactor technology was used as the basis for a new process for the conversion of natural gas to liquid products (Gas to Liquids or GTL). Economic analysis indicated that the new process could provide a 8-10% cost advantage over conventional technology. The economic prediction although favorable was not encouraging enough for a high risk program like this. Praxair decided to terminate development.

  6. Automated genome mining for natural products

    Directory of Open Access Journals (Sweden)

    Zajkowski James

    2009-06-01

    Full Text Available Abstract Background Discovery of new medicinal agents from natural sources has largely been an adventitious process based on screening of plant and microbial extracts combined with bioassay-guided identification and natural product structure elucidation. Increasingly rapid and more cost-effective genome sequencing technologies coupled with advanced computational power have converged to transform this trend toward a more rational and predictive pursuit. Results We have developed a rapid method of scanning genome sequences for multiple polyketide, nonribosomal peptide, and mixed combination natural products with output in a text format that can be readily converted to two and three dimensional structures using conventional software. Our open-source and web-based program can assemble various small molecules composed of twenty standard amino acids and twenty two other chain-elongation intermediates used in nonribosomal peptide systems, and four acyl-CoA extender units incorporated into polyketides by reading a hidden Markov model of DNA. This process evaluates and selects the substrate specificities along the assembly line of nonribosomal synthetases and modular polyketide synthases. Conclusion Using this approach we have predicted the structures of natural products from a diverse range of bacteria based on a limited number of signature sequences. In accelerating direct DNA to metabolomic analysis, this method bridges the interface between chemists and biologists and enables rapid scanning for compounds with potential therapeutic value.

  7. Regulation of natural health products in Canada.

    Science.gov (United States)

    Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

    2014-12-02

    In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Copy, edit, and paste: natural product approaches to biomaterials and neuroengineering.

    Science.gov (United States)

    Gademann, Karl

    2015-03-17

    Progress in the chemical sciences has formed the world we live in, both on a macroscopic and on a nanoscopic scale. The last century witnessed the development of high performance materials that interact with humans on many layers, from clothing to construction, from media to medical devices. On a molecular level, natural products and their derivatives influence many biological processes, and these compounds have enormously contributed to the health and quality of living of humans. Although coatings of stone materials with oils or resins (containing natural products) have led to improved tools already millennia ago, in contrast today, natural product approaches to designer materials, that is, combining the best of both worlds, remain scarce. In this Account, we will summarize our recent research efforts directed to the generation of natural product functionalized materials, exploiting the strategy of "copy, edit, and paste with natural products". Natural products embody the wisdom of evolution, and only total synthesis is able to unlock the secrets enshrined in their molecular structure. We employ total synthesis ("copy") as a scientific approach to address problems related to molecular structure, the biosynthesis of natural products, and their bioactivity. Additionally, the fundamental desire to investigate the mechanism of action of natural products constitutes a key driver for scientific inquiry. In an emerging area of relevance to society, we have prepared natural products such as militarinone D that can stimulate neurite outgrowth and facilitate nerve regeneration. This knowledge obtained by synthetic organic chemistry on complex natural products can then be used to design structurally simplified compounds that retain the biological power of the parent natural product ("edit"). This process, sometimes referred to as function-oriented synthesis, allows obtaining derivatives with better properties, improving their chemical tractability and reducing the step count

  9. Utilization of Natural Products as Functional Feed

    Directory of Open Access Journals (Sweden)

    Stella Magdalena

    2013-03-01

    Full Text Available The use of antibiotics as feed additive improves performance in livestock. However, scientific data related to the use of antibiotics in feed merge spreading of bacterial resistance in animal and human bodies, therefore the usage of antibiotics in animal production is restricted. This condition raise the utilization of natural antibiotic as functional feed such as phytogenics (essential oil, flavonoid, saponin, and tannin, enzyme, probiotic, and prebiotic to improve the livestock’s performance, quality, and health. Functional feeds increase profitability in animal husbandry production and its use is feeds are expected to be functional foods that may have positive effects in human nutrition.

  10. Polysaccharides and phytochemicals: a natural reservoir for the green synthesis of gold and silver nanoparticles.

    Science.gov (United States)

    Park, Y; Hong, Y N; Weyers, A; Kim, Y S; Linhardt, R J

    2011-09-01

    Currently, sustainability initiatives that use green chemistry to improve and/or protect our global environment are becoming focal issues in many fields of research. Instead of using toxic chemicals for the reduction and stabilisation of metallic nanoparticles, the use of various biological entities has received considerable attention in the field of nanobiotechnology. Among the many possible natural products, polysaccharides and biologically active plant products represent excellent scaffolds for this purpose. Polysaccharides have hydroxyl groups, a hemiacetal reducing end, and other functionalities that can play important roles in both the reduction and the stabilisation of metallic nanoparticles. Among the various categories of compounds in plants that have potent biological activities, phytochemicals are emerging as an important natural resource for the synthesis of metallic nanoparticles. The focus of this review is the application of polysaccharides and phytochemicals in the green synthesis of gold and silver nanoparticles to afford biocomposites with novel uses in nanomedicine and as nanocomposites.

  11. Methylaplysinopsin and other marine natural products affecting neurotransmission.

    Science.gov (United States)

    Taylor, K M; Baird-Lambert, J A; Davis, P A; Spence, I

    1981-01-01

    Methylaplysinopsin is a novel marine natural product that, after oral administration, prevented the effects of tetrabenazine in mice and rats. Methylaplysinopsin was a short-acting inhibitor of monoamine oxidase activity with greatest potency when serotonin was the substrate studied. The brain concentration of serotonin in the mouse was increased by methylaplysinopsin over the same time course as monoamine oxidase inhibition ex vivo. Methylaplysinopsin was also a weak inhibitor of the neuronal uptake of [3H]serotonin and a potentiator of the K+-induced release of [3H]serotonin from prelabeled synaptosomes. The predicted potentiation of serotonergic neurotransmission was supported by initial neurophysiological studies in an identified serotonergic pathway in the central nervous system of Aplysia. Two other studies on the pharmacology of marine natural products are reviewed. The majority of polyhalogenated monoterpenes isolated from red algae had central nervous system depressant properties. The exception is plocamadiene A, which caused, in mice, a reversible spastic paresis lasting up to 72 hours after oral administration. The severe muscle spasm was antagonized by diazepam. The final study discussed is the effect of a variety of marine natural products on the synthesis, neuronal uptake, and metabolism of GABA. Their selectivity is discussed with regard to the effects on metabolic respiration, and the correlation of neurochemical and neurophysiological effects on these marine substances.

  12. Trypanocidal Activity of Marine Natural Products

    Directory of Open Access Journals (Sweden)

    Amy J. Jones

    2013-10-01

    Full Text Available Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which very few drugs are currently available. This article will review the marine natural products for which activity against the kinetoplastid parasites; Trypanosoma brucei brucei, T.b. rhodesiense and T. cruzi has been reported. As it is important to know the selectivity of a compound when evaluating its trypanocidal activity, this article will only cover molecules which have simultaneously been tested for cytotoxicity against a mammalian cell line. Compounds have been grouped according to their chemical structure and representative examples from each class were selected for detailed discussion.

  13. Synthetic biological approaches to natural product biosynthesis.

    Science.gov (United States)

    Winter, Jaclyn M; Tang, Yi

    2012-10-01

    Small molecules produced in Nature possess exquisite chemical diversity and continue to be an inspiration for the development of new therapeutic agents. In their host organisms, natural products are assembled and modified using dedicated biosynthetic pathways. By rationally reprogramming and manipulating these pathways, unnatural metabolites containing enhanced structural features that were otherwise inaccessible can be obtained. Additionally, new chemical entities can be synthesized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds.

  14. Standardization for natural product synthetic biology.

    Science.gov (United States)

    Zhao, Huimin; Medema, Marnix H

    2016-08-27

    Standardization is one of the foundational features of modern-day engineering, and the use of standardized parts and processes is a key element that distinguishes bona fide synthetic biology from traditional genetic engineering. Here, we discuss the role of standardization in natural product synthetic biology, focusing on standardization of data on biosynthetic pathways and gene clusters, as well as the role of standardization in the process of biosynthetic gene cluster engineering.

  15. Natural Products as Sources for New Pesticides

    Science.gov (United States)

    2012-05-22

    A number of bio - chemical herbicides have been registered with the EPA since 1997. Horticultural vinegar, which consists of diluted aqueous solutions...However, this has not been the case for herbicides . Only one class of natural product-derived herbicide has been registered since 1997, namely, the...triketone herbicides . The discovery and development of these herbicides followed a fairly convoluted path that began in 1977 when Reed Gray at

  16. Natural cold pressed oils as cosmetic products

    Directory of Open Access Journals (Sweden)

    Małgorzata Ligęza

    2016-12-01

    Full Text Available Background. It seems that patients may ask general practitioners about natural cosmetics applied on the skin regarding their safety and suitability. Objectives. The aim of the study was to analyze natural cold pressed oils as potential cosmetic products. Material and methods. Cold pressed oils obtained from selected seeds and fruit stones were analyzed, including: chokeberry seed oil, blackcurrant seed oil, elderberry seed oil, raspberry seed oil, apricot seed oil, tomato seed oil, strawberry seed oil, broccoli seed oil, Nigella sativa seed oil, hemp oil, safflower seed oil, Silybum marianum seed oil and coconut oil. 80 adult volunteers assessed the cosmetic properties of the analyzed oils. Each of the volunteers tested 2 to 4 different oils, by applying them on the skin. In addition, patch tests with all analyzed oils were performed on 23 individuals. Results. The majority of tested oils were positively evaluated by the participants: in the opinion of the participants, oil extracted from safflower had the best appearance (100% positive opinions, coconut oil had the best smell (70% positive opinions, while black currant seed oil showed the best absorbency (85% positive opinions. No irritation was observed within the analyzed product group, albeit one allergic reaction to apricot seed oil was observed with patch testing. Conclusions . Based on the achieved results, it could be suggested that natural cold pressed oils can be applied to the skin as cosmetics. Our observations may be helpful for general practitioners when choosing natural cosmetics.

  17. Isolation of bioactive natural products from myxomycetes.

    Science.gov (United States)

    Ishibashi, Masami

    2005-11-01

    The Myxomycetes (true slime molds) are an unusual group of primitive organisms that may be assigned to one of the lowest classes of eukaryotes. As their fruit bodies are very small and it is very difficult to collect much quantity of slime molds, few studies have been made on the chemistry of myxomycetes. Cultivation of the plasmodium of myxomycetes in a practical scale for natural products chemistry studies is known only for very limited species. Here is described a review on the recent results on isolation of bioactive natural products from myxomycetes obtained in these two years in the laboratories. Spore germination experiments were studied of hundreds of field-collected myxomycetes collected in Japan and succeeded in laboratory culture of plasmodia of several myxomycetes in a practical scale for natural products chemistry studies. As a result, pyrroloiminoquinones, polyene yellow pigments, and a peptide lactone from cultured plasmodia of Didymium iridis, Physarum rigidum and P. melleum, respectively were isolated. New naphthoquinone pigments, cycloanthranilylprolines, tyrosine-kinase inhibitory bisindoles, and a cytotoxic triterpenoid aldehyde lactone were also isolated from field-collected fruit bodies of Cribraria purpurea, Fuligo candida, Tubifera casparyi, and Tubifera dimorphotheca, respectively.

  18. Marine natural products in prevention and treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Zahra Ghanbari

    2015-05-01

    Full Text Available Undoubtedly, pharmaceutical and nutritional factors play an important role in the prevention of age-related bone loss. According to the several studies so far, the effects of nutrients and bioactive components which are extracted from marine resources are very promising in osteoporosis. Most of these investigations have been done on various marine algae extracts. Since, algae are rich source of essential minerals, primary and secondary unique natural products, several amino acids and growth factors their extracts show favorable effects on bone metabolism. Moreover, it has been shown that marine nutrients such as marine fishes, shrimp and crabs increase the absorption of calcium and bone collagen synthesis or reduce the production of prostaglandins and decrease the deoxypyridinoline disposal. On the other hand, secondary products which are extracted and characterized from marine organisms such as mollusks, fungi, bacteria, sponges and coral reefs show anti-osteoporosis activities via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts like cells or stimulation of osteoblast differentiation. Although, several investigations have been done in this area, many of studies have been carried out on animal models, like ovariectomy-induced bone loss in mice. Hence, clinical investigations are warranted to develop marine natural products against bone loss and to prevent osteoporosis.

  19. Mimicking a natural pathway for de novo biosynthesis: natural vanillin production from accessible carbon sources.

    Science.gov (United States)

    Ni, Jun; Tao, Fei; Du, Huaiqing; Xu, Ping

    2015-09-02

    Plant secondary metabolites have been attracting people's attention for centuries, due to their potentials; however, their production is still difficult and costly. The rich diversity of microbes and microbial genome sequence data provide unprecedented gene resources that enable to develop efficient artificial pathways in microorganisms. Here, by mimicking a natural pathway of plants using microbial genes, a new metabolic route was developed in E. coli for the synthesis of vanillin, the most widely used flavoring agent. A series of factors were systematically investigated for raising production, including efficiency and suitability of genes, gene dosage, and culture media. The metabolically engineered strain produced 97.2 mg/L vanillin from l-tyrosine, 19.3 mg/L from glucose, 13.3 mg/L from xylose and 24.7 mg/L from glycerol. These results show that the metabolic route enables production of natural vanillin from low-cost substrates, suggesting that it is a good strategy to mimick natural pathways for artificial pathway design.

  20. Data Resources for the Computer-Guided Discovery of Bioactive Natural Products.

    Science.gov (United States)

    Chen, Ya; de Bruyn Kops, Christina; Kirchmair, Johannes

    2017-08-30

    Natural products from plants, animals, marine life, fungi, bacteria, and other organisms are an important resource for modern drug discovery. Their biological relevance and structural diversity make natural products good starting points for drug design. Natural product-based drug discovery can benefit greatly from computational approaches, which are a valuable precursor or supplementary method to in vitro testing. We present an overview of 25 virtual and 31 physical natural product libraries that are useful for applications in cheminformatics, in particular virtual screening. The overview includes detailed information about each library, the extent of its structural information, and the overlap between different sources of natural products. In terms of chemical structures, there is a large overlap between freely available and commercial virtual natural product libraries. Of particular interest for drug discovery is that at least ten percent of known natural products are readily purchasable and many more natural products and derivatives are available through on-demand sourcing, extraction and synthesis services. Many of the readily purchasable natural products are of small size and hence of relevance to fragment-based drug discovery. There are also an increasing number of macrocyclic natural products and derivatives becoming available for screening.

  1. Natural products as potential anticonvulsants: caffeoylquinic acids.

    Science.gov (United States)

    Kim, Hyo Geun; Oh, Myung Sook

    2012-03-01

    Current anticonvulsant therapies are generally directed at symptomatic treatment by suppressing excitability within the brain. Consequently, they have adverse effects such as cognitive impairment, dependence, and abuse. The need for more effective and less toxic anticonvulsants has generated renewed interest in natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are naturally occurring phenolic acids that are distributed widely in plants. There has been increasing interest in the biological activities of CQs in diseases of the central nervous system. In this issue, Nugroho et al. give evidence for the anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt. They optimized the extract solvent conditions, resulting in high levels of CQs and peroxynitrite-scavenging activity. Then, they investigated the sedative and anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed by onset time, tonic extent, and mortality. They suggested that the CQ-rich extract from A. glehni has potential for treating convulsions. This report provides preclinical data which may be used for the development of anticonvulsants from natural products.

  2. Phylogenetic approaches to natural product structure prediction.

    Science.gov (United States)

    Ziemert, Nadine; Jensen, Paul R

    2012-01-01

    Phylogenetics is the study of the evolutionary relatedness among groups of organisms. Molecular phylogenetics uses sequence data to infer these relationships for both organisms and the genes they maintain. With the large amount of publicly available sequence data, phylogenetic inference has become increasingly important in all fields of biology. In the case of natural product research, phylogenetic relationships are proving to be highly informative in terms of delineating the architecture and function of the genes involved in secondary metabolite biosynthesis. Polyketide synthases and nonribosomal peptide synthetases provide model examples in which individual domain phylogenies display different predictive capacities, resolving features ranging from substrate specificity to structural motifs associated with the final metabolic product. This chapter provides examples in which phylogeny has proven effective in terms of predicting functional or structural aspects of secondary metabolism. The basics of how to build a reliable phylogenetic tree are explained along with information about programs and tools that can be used for this purpose. Furthermore, it introduces the Natural Product Domain Seeker, a recently developed Web tool that employs phylogenetic logic to classify ketosynthase and condensation domains based on established enzyme architecture and biochemical function.

  3. Recent advances in the synthesis of natural multifunctionalized decalins.

    Science.gov (United States)

    Dhambri, S; Mohammad, S; Van Buu, O Nguyen; Galvani, G; Meyer, Y; Lannou, M-I; Sorin, G; Ardisson, J

    2015-06-01

    This review highlights recent innovative synthetic strategies developed for the stereoselective construction of natural complex decalin systems. It offers an insight into various synthetic targets and approaches and provides information for developments within the area of natural products as well as synthetic methodology.

  4. Natural products research in latin america.

    Science.gov (United States)

    Gupta, M P

    2001-01-01

    The biodiversity found in Latin America is one of the richest in the world, yet its potential as a source of new pharmaceuticals has not been fully investigated. This paper will explore the present status of natural products research in 19 Latin American countries. Future research needs will be presented along with reports on the ethnobotanical and bioprospection projects under way in Latin America. The presentation will be based on data collected over the last five years and will be presented within the framework of the Fine Pharmaceutical Subprogram of the Iberoamerican Program of Science and Technology for Development (CYTED), a novel international cooperation program.

  5. The Rakicidin Family of Anticancer Natural Products

    DEFF Research Database (Denmark)

    Tsakos, Michail; Jacobsen, Kristian Mark; Yu, Wanwan

    2016-01-01

    Rakicidin A is a prominent member of a small class of macrocyclic lipodepsipeptide natural products that contain an electrophilic 4- amido-2,4-pentadienoate (APD) functionality. Rakicidin A displays selective growth inhibitory activity against hypoxic cancer cells as well as imatinib......-resistant chronic myelogenous leukemia (CML) cells. In this paper we present and discuss the two known synthetic routes to rakicidin A, which provide an instructive comparison of strategies used to address the synthetic challenges inherent to rakicidin A. In addition to the synthetic discussion we provide a status...

  6. Natural products from microbes associated with insects

    Directory of Open Access Journals (Sweden)

    Christine Beemelmanns

    2016-02-01

    Full Text Available Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We demonstrate that the exploration of specific microbial–host interactions, in combination with multidisciplinary dereplication processes, has emerged as a successful strategy to identify novel chemical entities and to shed light on the ecology and evolution of defensive associations.

  7. Cell-Free Synthesis Meets Antibody Production: A Review

    Directory of Open Access Journals (Sweden)

    Marlitt Stech

    2015-01-01

    Full Text Available Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv and antigen binding fragments (Fab, have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.

  8. Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms.

    Science.gov (United States)

    Büschleb, Martin; Dorich, Stéphane; Hanessian, Stephen; Tao, Daniel; Schenthal, Kyle B; Overman, Larry E

    2016-03-18

    Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quaternary carbon atoms in their intricate structures are reviewed with 12 representative examples. Emphasis has been put on methods to create quaternary carbon stereocenters, including syntheses of the same natural product by different groups, thereby showcasing the diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quaternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information.

  9. Production of biofuels from synthesis gas using microbial catalysts.

    Science.gov (United States)

    Tirado-Acevedo, Oscar; Chinn, Mari S; Grunden, Amy M

    2010-01-01

    World energy consumption is expected to increase 44% in the next 20 years. Today, the main sources of energy are oil, coal, and natural gas, all fossil fuels. These fuels are unsustainable and contribute to environmental pollution. Biofuels are a promising source of sustainable energy. Feedstocks for biofuels used today such as grain starch are expensive and compete with food markets. Lignocellulosic biomass is abundant and readily available from a variety of sources, for example, energy crops and agricultural/industrial waste. Conversion of these materials to biofuels by microorganisms through direct hydrolysis and fermentation can be challenging. Alternatively, biomass can be converted to synthesis gas through gasification and transformed to fuels using chemical catalysts. Chemical conversion of synthesis gas components can be expensive and highly susceptible to catalyst poisoning, limiting biofuel yields. However, there are microorganisms that can convert the CO, H(2), and CO(2) in synthesis gas to fuels such as ethanol, butanol, and hydrogen. Biomass gasification-biosynthesis processing systems have shown promise as some companies have already been exploiting capable organisms for commercial purposes. The discovery of novel organisms capable of higher product yield, as well as metabolic engineering of existing microbial catalysts, makes this technology a viable option for reducing our dependency on fossil fuels.

  10. Natural Products: Insights into Leishmaniasis Inflammatory Response

    Science.gov (United States)

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  11. Near infrared spectroscopy in natural products analysis.

    Science.gov (United States)

    Cozzolino, Daniel

    2009-06-01

    Several medicinal and herbal plants properties are related to individual compounds such as essential oils, terpenoids, flavonoids, which are present in natural products in low concentrations (e. g., ppm or ppb). For many years, the use of classical separation and chromatographic and spectrometric techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), liquid chromatography (LC) and mass spectrometry (MS) were initially used for the elucidation of isolated compounds from different plant matrices. Spectroscopic techniques in the infrared (IR) wavelength region of the electromagnetic spectrum have been used in the food industry to monitor and evaluate the composition of foods. Although Herschel discovered light in the near-infrared (NIR) region as early as 1800, most spectroscopists of the first half of the last century ignored it, in the belief that it lacked any analytical interest. However, during the last 40 years NIR spectroscopy has become one of the most attractive and used methods for analysis. This mini-review highlights recent applications of NIR spectroscopy to the qualitative and quantitative analysis of plant natural products.

  12. Pyranone natural products as inspirations for catalytic reaction discovery and development.

    Science.gov (United States)

    McDonald, Benjamin R; Scheidt, Karl A

    2015-04-21

    Natural products continue to provide a wealth of opportunities in the areas of chemical and therapeutic development. These structures are effective measuring sticks for the current state of chemical synthesis as a field and constantly inspire new approaches and strategies. Tetrahydropryans and tetrahydropyran-4-ones are found in numerous bioactive marine natural products and medicinal compounds. Our interest in exploring the therapeutic potential of natural products containing these motifs provided the impetus to explore new methods to access highly functionalized, chiral pyran molecules in the most direct and rapid fashion possible. This goal led to exploration and development of a Lewis acid-mediated Prins reaction between a chiral β-hydroxy-dioxinone and aldehyde to produce a pyran-dioxinone fused product that can be processed in a single pot operation to the desired tetrahydropyran-4-ones in excellent yield and stereoselectivity. Although the Prins reaction is a commonly employed approach toward pyrans, this method uniquely provides a 3-carboxy-trisubstituted pyran and utilizes dioxinones in a manner that was underexplored at the time. The 3-carboxy substituent served as a key synthetic handhold when this method was applied to the synthesis of highly functionalized pyrans within the macrocyclic natural products neopeltolide, okilactiomycin, and exiguolide. When employed in challenging macrocyclizations, this tetrahydropyranone forming reaction proved highly stereoselective and robust. Another major thrust in our lab has been the synthesis of benzopyranone natural products, specifically flavonoids, because this broad and diverse family of compounds possesses an equally broad range of biological and medicinal applications. With the goal of developing a broad platform toward the synthesis of enantioenriched flavonoid analogs and natural products, a biomimetic, asymmetric catalytic approach toward the synthesis of 2-aryl benzopyranones was developed. A

  13. Natural Gas and Cellulosic Biomass: A Clean Fuel Combination? Determining the Natural Gas Blending Wall in Biofuel Production.

    Science.gov (United States)

    M Wright, Mark; Seifkar, Navid; Green, William H; Román-Leshkov, Yuriy

    2015-07-07

    Natural gas has the potential to increase the biofuel production output by combining gas- and biomass-to-liquids (GBTL) processes followed by naphtha and diesel fuel synthesis via Fischer-Tropsch (FT). This study reflects on the use of commercial-ready configurations of GBTL technologies and the environmental impact of enhancing biofuels with natural gas. The autothermal and steam-methane reforming processes for natural gas conversion and the gasification of biomass for FT fuel synthesis are modeled to estimate system well-to-wheel emissions and compare them to limits established by U.S. renewable fuel mandates. We show that natural gas can enhance FT biofuel production by reducing the need for water-gas shift (WGS) of biomass-derived syngas to achieve appropriate H2/CO ratios. Specifically, fuel yields are increased from less than 60 gallons per ton to over 100 gallons per ton with increasing natural gas input. However, GBTL facilities would need to limit natural gas use to less than 19.1% on a LHV energy basis (7.83 wt %) to avoid exceeding the emissions limits established by the Renewable Fuels Standard (RFS2) for clean, advanced biofuels. This effectively constitutes a blending limit that constrains the use of natural gas for enhancing the biomass-to-liquids (BTL) process.

  14. Collaboration and Productivity in Scientific Synthesis

    Science.gov (United States)

    Hampton, Stephanie E.; Parker, John N.

    2011-01-01

    Scientific synthesis has transformed ecological research and presents opportunities for advancements across the sciences; to date, however, little is known about the antecedents of success in synthesis. Building on findings from 10 years of detailed research on social interactions in synthesis groups at the National Center for Ecological Analysis…

  15. Yoghurt enrichment with natural bee farming products

    Directory of Open Access Journals (Sweden)

    N. Lomova

    2015-05-01

    Full Text Available Introduction. Bee pollen is a unique and unparalleled natural bioactive substances source. Using it in conjunction with the popular functional fermented milk product -yogurt will expand its product range and increase the biological value. Materials and Methods. Dried bee pollen’s moisture determination was made by gravimetry methods, based on the sample weight loss due to desiccation, until constant weight was reached.Test and control yogurt samples were studied by applying standard techniques for milk and milk products set forth in the regulations of Ukraine. Results and discussion. It is found that bee pollen pellet drying to a moisture content of 2 -4%, increases the flow rate of powder almost by 90%. The sample having moisture content of 2% will have a bulk density exceeding 12.5% compared to the sample having moisture content of 10%. Raw output will also increase by 3.7%. By contrast, apparent density and weight fraction of losses decreases, which has a positive impact on pollen efficiency of use and distribution in bulk yogurt. Moreover, the weight fraction of losses decreases by fourfold (4.6% vs. 1%. It was experimentally determined that pollen can deteriorate microbiological characteristics of yogurt. It was proved that treatment of crushed bee pollen pellet sample with ultraviolet allows improving yogurt microbiological safety indicators. Namely, to reduce the presence of coli-forms to 0, mould –to 10 CFU/cm³. Conclusions. The proposed bee pollen pellet treatment method will improve the technological and microbiological characteristics of pollen powder. This provides for yoghurt production biotechnology using bee farming products.

  16. Potential anti-inflammatory natural products from marine algae.

    Science.gov (United States)

    Fernando, I P Shanura; Nah, Jae-Woon; Jeon, You-Jin

    2016-12-01

    Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Synthesis and characterization of the natural and burned hydrotalcite; Sintesis y caracterizacion de la hidrotalcita natural y calcinada

    Energy Technology Data Exchange (ETDEWEB)

    Granados C, F. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The synthesis and the structural and surface properties of the natural and burned hydrotalcite using salts of AlCl{sub 3} and MgCl{sub 2}.6H{sub 2}O its were studied. Its were used those analysis of BET, IR, XRD, TGA and SEM to characterize these materials. The obtained product was identified as the natural or carbonated hydrotalcite of chemical formula Mg{sub 6}Al{sub 2}(OH){sub 16}CO{sub 3}.4H{sub 2}O. The hydrotalcite was roasted at 500 C during 5 h and the was obtained roasted hydrotalcite (HTC) that is a material of high selectivity toward the anions that it can be efficiently used as adsorbent material in studies of adsorption for the treatment of anionic radioactive waste present in watery solution. (Author)

  18. Conference Report: ESF-COST High-Level Research Conference Natural Products Chemistry, Biology and Medicine III.

    Science.gov (United States)

    Catino, Arthur

    2010-12-01

    Natural Products Chemistry, Biology and Medicine III was the third conference in a series of events sponsored by the European Science Foundation (ESF) and the European Cooperation in the field of Scientific and Technical Research (COST). Scientists came together from within and outside the EU to present cutting-edge developments in chemical synthesis. Research areas included the synthesis of natural products, methods development, isolation/structural elucidation and chemical biology. As our capacity to produce new chemotherapeutic agents relies on chemical synthesis, this year's conference has never been so timely. This report highlights several of the scientific contributions presented during the meeting.

  19. The automation of natural product structure elucidation.

    Science.gov (United States)

    Steinbeck, C

    2001-05-01

    The last two or three years have seen exciting developments in the field of computer-assisted structure elucidation (CASE) with a number of programs becoming commercially or freely available. This was the conditio sine qua non for CASE to be widely applied in the daily work of bench chemists and spectroscopists. A number of promising applications have been published in the area of structure generators, deterministic and stochastic CASE tools and property predictions, including the automatic distinction between natural products and artificial compounds, as well as the determination of 3-D structure from a connection table based on IR spectroscopy. Advancements in coupling techniques between chromatographic and spectroscopic methods demonstrate progress towards a fully automated structure elucidation or identification process starting at the earliest steps of obtaining crude extracts.

  20. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

    Science.gov (United States)

    Tran, Anh T.; Watson, Emma E.; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J.; Giltrap, Andrew M.; Pang, Angel; Wong, Weng Ruh; Linington, Roger G.; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A.; West, Nicholas P.; Bugg, Timothy D. H.; Tod, Julie; Dowson, Christopher G.; Roper, David I.; Crick, Dean C.; Britton, Warwick J.; Payne, Richard J.

    2017-03-01

    Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.

  1. Target identification of natural products and bioactive compounds using affinity-based probes.

    Science.gov (United States)

    Pan, Sijun; Zhang, Hailong; Wang, Chenyu; Yao, Samantha C L; Yao, Shao Q

    2016-05-04

    Covering: 2010 to 2014.Advances in isolation, synthesis and screening strategies have made many bioactive substances available. However, in most cases their putative biological targets remain unknown. Herein, we highlight recent advances in target identification of natural products and bioactive compounds by using affinity-based probes. Aided by photoaffinity labelling, this strategy can capture potential cellular targets (on and off) of a natural product or bioactive compound in live cells directly, even when the compound-target interaction is reversible with moderate affinity. The knowledge of these targets may help uncover molecular pathways and new therapeutics for currently untreatable diseases. In this highlight, we will introduce the development of various photoactivatable groups, their synthesis and applications in target identification of natural products and bioactive compounds, with a focus on work done in recent years and from our laboratory. We will further discuss the strengths and weaknesses of each group and the outlooks for this novel proteome-wide profiling strategy.

  2. Chemistry of natural products: A veritable approach to the ...

    African Journals Online (AJOL)

    Chemistry of natural products: A veritable approach to the development of drugs for combating ... PROMOTING ACCESS TO AFRICAN RESEARCH ... The earth's resources, especially natural products, are no doubt important materials from ...

  3. Chocolate: A Marvelous Natural Product of Chemistry

    Science.gov (United States)

    Tannenbaum, Ginger

    2004-08-01

    Chocolate is a natural product as ubiquitous as television. Of course, it is eaten, but it is also found in air fresheners, marking pens, flavoring in a multitude of products including soda pop, and as an aroma in "chocolate-dyed" T-shirts. However, most of us are completely unaware of the complex chemical reactions that take place to produce chocolate and the necessary technology that has evolved to produce chocolate and all its byproducts. Processing results in a mixture of many components, an interesting contrast to most of the simple, one-step reactions introduced at the high school level. This article is a survey of chocolate from tree to table. After a brief introduction to the history of chocolate and how and where it is grown, the manufacturing process is examined, and the chemistry is explored. A bit of the jargon used in the industry is mentioned. Cocoa butter is a significant ingredient in chocolate, and an investigation of it introduces triglycerides, fatty acids, polymorphic behavior, and molecular packing of the fats in chocolate and how they affect the tempering process. There is a brief discussion of chocolate's non-Newtonian behavior and the resulting challenges presented in the manufacturing process. See Featured Molecules Featured on the Cover

  4. Biocombinatorial Engineering of Fungal PKS-NRPS Hybrids for Production of Novel Synthetic Natural Products

    DEFF Research Database (Denmark)

    Nielsen, Maria Lund

    . Secondary metabolites (SMs) from bacteria, plants and filamentous fungi constitute a large group of important natural products. In this thesis I explore the biosynthesis of several fungal SMs along with the enzymes responsible for their synthesis. Specifically, my research focuses on the expression...... and engineering of a certain type of fungal enzymes – natural fusions of polyketide synthases and nonribosomal peptide synthetases (PKS-NRPSs). The thesis is divided into two topics: 1) Expanding fungal chemodiversity through combinatorial biosynthesis 2) Two CRISPR-Cas9-based approaches to linking SMs...... and NRPS modules. In the third study (chapter 4), I describe how CRISPR-Cas9, which was recently implemented for genome editing in filamentous fungi, can be used to link SMs to their genetic origin in a fungus where no genetic tools were previously available. Using CRISPR-Cas9, I identified a novel gene...

  5. Synthesis and characterization of natural red dye from Caesalpinia sappan linn

    Energy Technology Data Exchange (ETDEWEB)

    Mulyanto, Subur, E-mail: subur.mulyanto@poltekba.ac.id [Graduate Program of Mechanical Engineering, SebelasMaret University, Jl. Ir. Sutami 36 A, Surakarta (Indonesia); Department of Mechanical Engineering, State Polytechnic of Balikpapan, Jl. Soekarno-Hatta Km.8 Balikpapan (Indonesia); Suyitno,, E-mail: suyitno@uns.ac.id; Rachmanto, Rendy Adhi, E-mail: rendy.ar@gmail.com; Hidayat, Lullus Lambang Govinda, E-mail: lulus-l@yahoo.com; Hadi, Syamsul, E-mail: syamsulhadi@ft.uns.ac.id [Department of Mechanical Engineering, SebelasMaret University, Jl. Ir. Sutami 36 A, Surakarta (Indonesia); Wibowo, Atmanto Heru, E-mail: aheruwibowo@yahoo.com [Department of Chemistry, SebelasMaret University, Jl. Ir. Sutami 36 A, Surakarta (Indonesia)

    2016-03-29

    The study reports the synthesis and characterization of natural red dye. The dyes were extracted from woods of Caesalpiniasappanlinn at varied temperatures of 70, 80, 90, and 100°C for three hours. The dry wood chips and water at a ratio of 6:1 were immersed in the reactor of 150 liters. The absorbance spectra of the natural red dyes were measured by ultra-violet-visible spectroscopy. Meanwhile, Fourier transform infrared spectroscopy was used to investigate the functional groups of the natural red dyes. In addition, the basic production cost was calculated and the fastness property towards cotton fabrics was investigated according to the Indonesia national standard of 105-C06:2010, 105-B01:2010, and 0288-2008. The results showed that the functional groups found the extracted red dyes indicated the complex bond of brazilein with peak absorbance at a wavelength of 538-540 nm. The extraction temperature also changed the functional group of brazilein. From the color, the absorbance peak, the functional groups, and the main production cost, the best parameter to synthesize the natural red dyes from Caesalpiniasappanlinn was at a temperature of 80°C for two hours. Moreover, the natural red dyes has the fastness to wash resistance, light resistance, and scrub resistance by 4-5, 4, and 3-4, respectively. However, further studies for synthesis the natural red dyes by using a continuous reactor are required to identify the naturally complex compounds in brazilein for improving the fastness properties and for reducing the cost.

  6. Synthesis and characterization of natural red dye from Caesalpinia sappan linn

    Science.gov (United States)

    Mulyanto, Subur; Suyitno, Rachmanto, Rendy Adhi; Hidayat, Lullus Lambang Govinda; Wibowo, Atmanto Heru; Hadi, Syamsul

    2016-03-01

    The study reports the synthesis and characterization of natural red dye. The dyes were extracted from woods of Caesalpiniasappanlinn at varied temperatures of 70, 80, 90, and 100°C for three hours. The dry wood chips and water at a ratio of 6:1 were immersed in the reactor of 150 liters. The absorbance spectra of the natural red dyes were measured by ultra-violet-visible spectroscopy. Meanwhile, Fourier transform infrared spectroscopy was used to investigate the functional groups of the natural red dyes. In addition, the basic production cost was calculated and the fastness property towards cotton fabrics was investigated according to the Indonesia national standard of 105-C06:2010, 105-B01:2010, and 0288-2008. The results showed that the functional groups found the extracted red dyes indicated the complex bond of brazilein with peak absorbance at a wavelength of 538-540 nm. The extraction temperature also changed the functional group of brazilein. From the color, the absorbance peak, the functional groups, and the main production cost, the best parameter to synthesize the natural red dyes from Caesalpiniasappanlinn was at a temperature of 80°C for two hours. Moreover, the natural red dyes has the fastness to wash resistance, light resistance, and scrub resistance by 4-5, 4, and 3-4, respectively. However, further studies for synthesis the natural red dyes by using a continuous reactor are required to identify the naturally complex compounds in brazilein for improving the fastness properties and for reducing the cost.

  7. [The recent research progress of chemistry of marine natural products].

    Science.gov (United States)

    Shi, Qing-wen; Li, Li-geng; Wang, Yu-fang; Huo, Chang-hong; Zhang, Man-li

    2010-10-01

    Ocean is a unique and excellent resource that provides a diverse array of intriguing natural products. Marine natural products have demonstrated significant and extremely potent biological activities and have captured the attention of natural products chemists in the past few decades. It is increasingly recognized that a wealth of fascinating natural products and novel chemical entities will play a dominant role in the discovery of useful leads for the development of pharmaceutical agents and provide useful probes to lead to breakthroughs in a variety of life-science fields. This article focused on the research progress of chemistry of marine natural products in recent five years.

  8. Natural Product Research in the Australian Marine Invertebrate Dicathais orbita

    Directory of Open Access Journals (Sweden)

    Kirsten Benkendorff

    2013-04-01

    Full Text Available The predatory marine gastropod Dicathais orbita has been the subject of a significant amount of biological and chemical research over the past five decades. Natural products research on D. orbita includes the isolation and identification of brominated indoles and choline esters as precursors of Tyrian purple, as well as the synthesis of structural analogues, bioactivity testing, biodistributional and biosynthetic studies. Here I also report on how well these compounds conform to Lipinski’s rule of five for druglikeness and their predicted receptor binding and enzyme inhibitor activity. The composition of mycosporine-like amino acids, fatty acids and sterols has also been described in the egg masses of D. orbita. The combination of bioactive compounds produced by D. orbita is of interest for further studies in chemical ecology, as well as for future nutraceutical development. Biological insights into the life history of this species, as well as ongoing research on the gene expression, microbial symbionts and biosynthetic capabilities, should facilitate sustainable production of the bioactive compounds. Knowledge of the phylogeny of D. orbita provides an excellent platform for novel research into the evolution of brominated secondary metabolites in marine molluscs. The range of polarities in the brominated indoles produced by D. orbita has also provided an effective model system used to develop a new method for biodistributional studies. The well characterized suite of chemical reactions that generate Tyrian purple, coupled with an in depth knowledge of the ecology, anatomy and genetics of D. orbita provide a good foundation for ongoing natural products research.

  9. Relative stereochemical determination and synthesis of the C1-C17 fragment of a new natural polyketide.

    Science.gov (United States)

    Fleury, Etienne; Lannou, Marie-Isabelle; Bistri, Olivia; Sautel, François; Massiot, Georges; Pancrazi, Ange; Ardisson, Janick

    2009-09-18

    The challenging determination of the relative stereochemistry of a complex natural polyketide portion was achieved. After careful NMR analysis, a concise synthesis of a set of possible relative diastereomers (only 6 diastereomers out of the 32 initially envisioned) has been carried out using a common strategy based on enantioselective aldol reactions. With a high predictability, final NMR comparison established the relative stereochemistry of the C1-C17 fragment of this natural product.

  10. Efficient synthesis of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol.

    Science.gov (United States)

    Sun, Hong-Yi; Xiao, Chun-Fen; Cai, Yu-Chen; Chen, Yu; Wei, Wen; Liu, Xian-Ke; Lv, Ze-Liang; Zou, Yong

    2010-11-01

    The practical synthesis of important natural polyphenolic stilbenes, including resveratrol, piceatannol and oxyresveratrol, through Perkin methodology is described. Starting from 3,5-dihydoxyacetophenone (1), the common intermediate 3,5-dimethoxyphenylacetic acid (3) can be obtained via methylation and Willgerodt-Kindler reaction. Perkin condensations between (3) and substituted phenylaldehydes 4 furnished E-2,3-diarylacrylic acids 5, followed by decarboxylation in Cu/quinoline giving stilbene intermediates 6 which bear the Z-configuration. Finally, through a simultaneous demethylation/isomerization process in AlI₃/CH₃CN system, the target compounds 7a-c can be obtained respectively in good to high overall yields. The synthetic method proved to be more concise, trans-specific, mild, economical and commonly applicable.

  11. Synthesis and activation of Immobilized beads by natural dye extracts

    Directory of Open Access Journals (Sweden)

    Singh Sanjay

    2012-03-01

    Full Text Available Immobilization technique is used for preservation of enzymes. Here we are using different colors of natural dye in this technique. Our major emphasis would be to create beads of different colors which will act as different carriers for essential enzymes. The need for using colorful dye is because when we need to preserve more than one enzyme then it is helpful in identification of that which enzyme is to be preserved and in which color. Here we used natural dye because most of the chemical dyes are carcinogenic in nature and may alter the nature of preserved enzyme. For this different plant products like mint leaf, rose petal, beat root and Carrot are used for the extraction of dye. In our research studies, we have identified, extracted, characterized, optimized and standardized the natural dyes from plant and microbial sources and we did a comparative study between natural dyes and artificial dyes with respect to different solvent systems like petroleum ether, diethyl ether, acetone, chloroform, ethanol and water systems. The extraction methodologies, characterization, MIC (minimum inhibitory concentration, and solubility studies will be discussed. These immobilization studies will help us to use this application in a variety of fields like in wine stabilization, in modifying the shelf life of food and other natural products which degrade quickly and are difficult to preserve under natural conditions. Here sodium Alginate beads are being used so that there is good number of beads formation and that will help for the proper entrapment of the essential enzymes required for an important reaction in Bio-systems.

  12. Product engineering by high-temperature flame synthesis

    DEFF Research Database (Denmark)

    Johannessen, Tue; Johansen, Johnny; Mosleh, Majid;

    High-temperature flame processes can be applied as a tool for chemical product engineering. The general principle behind flame synthesis is the decomposition/oxidation of evaporated metal-precursors in a flame, thereby forming metal oxide monomers which nucleate, aggregate, and - to some extent...... product gas can be applied directly in additional product engineering concepts. A brief overview of on-going product developments and product engineering projects is outlined below. These projects, which are all founded on flame synthesis of nano-structured materials, include: • Preparation of catalyzed...

  13. Synthesis and characterization of zeolite A by hydrothermal transformation of natural Jordanian kaolin

    Directory of Open Access Journals (Sweden)

    Mousa Gougazeh

    2014-04-01

    Full Text Available The synthesis of zeolite materials by hydrothermal transformation of natural Jordanian kaolin in NaOH solutions of various concentrations was investigated at 100 °C for 20 h. A mixture of zeolite A, quartz and hydroxysodalite (HS was obtained. Zeolite A was the main product with the NaOH concentrations of 1.50–3.50 M, which was confirmed by XRD, IR and SEM. Zeolite A can be obtained from natural kaolin under the conditions applied showing that metakaolinization can be observed at 650 °C which is much lower than the temperatures given in the previous works, 700–950 °C. The products obtained from the experiments were characterized by X-ray diffraction (XRD, Fourier transform infrared spectroscopy (FTIR and scanning electron microscopy (SEM.

  14. Beware When Buying "All Natural" Erectile Dysfunction Products

    Science.gov (United States)

    ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Home For Consumers Protect Yourself Health Fraud Beware When Buying "All Natural" Erectile Dysfunction Products Share Tweet Linkedin Pin it ...

  15. Oxygen-containing fragments in natural products.

    Science.gov (United States)

    Titarenko, Zoya; Vasilevich, Natalya; Zernov, Vladimir; Kirpichenok, Michael; Genis, Dmitry

    2013-02-01

    An analysis of the chemical environment of the oxygen atoms in the DNP database compared to the CMC and SCD databases was performed. Some structural clusters were identified which are predominant among the natural products and can be considered as distinctive features of NPs. Fifty-three oxygen-containing structural fragments that are distinctive for the DNP (distinctive set of fragments DSF) in comparison with the SCD have been identified. A new descriptor Mc was introduced for describing the ratio of atoms involved in the DSF to the total number of heavy atoms. A significant difference in the Mc values among the reference databases allowed the use of a specific cluster of the DSF as a tool for performing similarity searches for oxygen-containing NP molecules, or for evaluation or comparison of databases according to their NP-likeness. An example illustrating that the suggested approach could allow not only estimating the NP-likeness, but also serve as a tool for designing new NP-like compounds is provided. The suggested approach for NP-likeness evaluation moves away from the traditional ideas of scaffolds, cycles, linkers and substituents.

  16. Antifouling Activity of Marine Natural Products

    KAUST Repository

    Qian, Pei-Yuan

    2012-01-01

    With the global ban of application of organotin-based marine coatings by International Maritime Organization in 2008, there is a practical and urgent need of identifying environmentally friendly low-toxic and nontoxic antifouling compounds for marine industries. Marine natural products have been considered as one of the most promising sources of antifouling compounds in recent years. In antifouling compound screening processes, bioassay systems often play most critical/vital roles in screening efforts. To meet various needs, a variety of bioassay systems have been developed and/or adopted in both research and commercial laboratories. In this chapter, we provide a brief outline of common bioassay procedures for both antimicrofouling and antimacrofouling assays, which can serve as a general guideline for setting up bioassay systems in laboratories engaged in antifouling compound screening. Some bioassay procedures currently practiced in various laboratories are not included in this book chapter for various reasons. Individual laboratories should modify bioassay protocols based on their research interests or needs. Nevertheless, we highly recommend the research laboratories to adapt high-throughput assays as much as possible for preliminary screening assays, followed by more complex bioassay processes using multiple target species. We argue strongly for studies in mode-of-action of antifouling compounds against settling propagules, which shall lead to discovery of molecular biomarkers (genes, proteins, receptors, or receptor system) and will allow us to design more targeted bioassay systems.

  17. A Historical Overview of Natural Products in Drug Discovery

    Science.gov (United States)

    Dias, Daniel A.; Urban, Sylvia; Roessner, Ute

    2012-01-01

    Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed. PMID:24957513

  18. Diversity of nature's assembly lines - recent discoveries in non-ribosomal peptide synthesis.

    Science.gov (United States)

    Payne, Jennifer A E; Schoppet, Melanie; Hansen, Mathias Henning; Cryle, Max J

    2016-12-20

    The biosynthesis of complex natural products by non-ribosomal peptide synthetases (NRPSs) and the related polyketide synthases (PKSs) represents a major source of important bioactive compounds. These large, multi-domain machineries are able to produce a fascinating range of molecules due to the nature of their modular architectures, which allows natural products to be assembled and tailored in a modular, step-wise fashion. In recent years there has been significant progress in characterising the important domains and underlying mechanisms of non-ribosomal peptide synthesis. More significantly, several studies have uncovered important examples of novel activity in many NRPS domains. These discoveries not only greatly increase the structural diversity of the possible products of NRPS machineries but - possibly more importantly - they improve our understanding of what is a highly important, yet complex, biosynthetic apparatus. In this review, several recent examples of novel NRPS function will be introduced, which highlight the range of previously uncharacterised activities that have now been detected in the biosynthesis of important natural products by these mega-enzyme synthetases.

  19. Phthalides: Distribution in Nature, Chemical Reactivity, Synthesis, and Biological Activity.

    Science.gov (United States)

    León, Alejandra; Del-Ángel, Mayela; Ávila, José Luis; Delgado, Guillermo

    oxidation, reduction, addition, elimination, and cycloaddition reactions, and treatments with Lewis acids of (Z)-ligustilide have afforded linear dimers. Some intramolecular condensations and differentiated cyclizations of the dimeric phthalides have been carried out, providing evidences for the particular chemical reactivity of these compounds.Several structural modifications of phthalides have been carried out subjecting them to microbial transformations by different species of bacteria, fungi and algae, and these included resolutions of racemic mixtures and oxidations, among others.The [π4s + π2s] and [π2s + π2s] cycloadditions of (Z)-ligustilide for the synthesis of dimeric phthalides have been reported, and different approaches involving cyclizations, Alder-Rickert reactions, Sharpless asymmetric hydroxylations, or Grignard additions have been used for the synthesis of monomeric phthalides. The use of phthalides as building blocks for divergent oriented synthesis has been proven.Many of the naturally occurring phthalides display different biological activities including antibacterial, antifungal, insecticidal, cytotoxic, and anti-inflammatory effects, among many others, with a considerable recent research on the topic. In the case of compounds isolated from the Apiaceae, the bioactivities correlate with the traditional medicinal uses of the natural sources. Some monomeric phthalides have shown their ability to attenuate certain neurological diseases, including stroke, Alzheimer's and Parkinson's diseases.The present contribution covers the distribution of phthalides in nature and the findings in the structural diversity, chemical reactivity, biotransformations, syntheses, and bioactivity of natural and semisynthetic phthalides.

  20. Using product driven process synthesis in the biorefinery

    NARCIS (Netherlands)

    Kiskini, A.; Zondervan, E.; Wierenga, P.A.; Poiesz, E.; Gruppen, H.

    2015-01-01

    In this work, we propose the use of the product-driven process synthesis (PDPS) methodology for the product and process design stage in biorefinery. The aim of the biorefinery is to optimize the total use of the whole feedstock – with focus being on various products simultaneously – rather than to

  1. Mycolic Acid-Containing Bacteria Induce Natural-Product Biosynthesis in Streptomyces Species▿ †

    Science.gov (United States)

    Onaka, Hiroyasu; Mori, Yukiko; Igarashi, Yasuhiro; Furumai, Tamotsu

    2011-01-01

    Natural products produced by microorganisms are important starting compounds for drug discovery. Secondary metabolites, including antibiotics, have been isolated from different Streptomyces species. The production of these metabolites depends on the culture conditions. Therefore, the development of a new culture method can facilitate the discovery of new natural products. Here, we show that mycolic acid-containing bacteria can influence the biosynthesis of cryptic natural products in Streptomyces species. The production of red pigment by Streptomyces lividans TK23 was induced by coculture with Tsukamurella pulmonis TP-B0596, which is a mycolic acid-containing bacterium. Only living cells induced this pigment production, which was not mediated by any substances. T. pulmonis could induce natural-product synthesis in other Streptomyces strains too: it altered natural-product biosynthesis in 88.4% of the Streptomyces strains isolated from soil. The other mycolic acid-containing bacteria, Rhodococcus erythropolis and Corynebacterium glutamicum, altered biosynthesis in 87.5 and 90.2% of the Streptomyces strains, respectively. The coculture broth of T. pulmonis and Streptomyces endus S-522 contained a novel antibiotic, which we named alchivemycin A. We concluded that the mycolic acid localized in the outer cell layer of the inducer bacterium influences secondary metabolism in Streptomyces, and this activity is a result of the direct interaction between the mycolic acid-containing bacteria and Streptomyces. We used these results to develop a new coculture method, called the combined-culture method, which facilitates the screening of natural products. PMID:21097597

  2. Pharmaceuticals from natural products: current trends

    Directory of Open Access Journals (Sweden)

    PETER R. SEIDL

    2002-03-01

    Full Text Available The use of products extracted from plants for medicinal purposes can be traced to the beginnings of civilization and up until the end of the nineteenth century natural products were the principal source of medicines. Since then their relative importance has oscillated according to the strategies of large pharmaceutical companies. Now that these strategies are changing, there are new opportunities for countries like Brazil, in which a large proportion of the world's biodiversity is located. There are, however, new circumstances that must be taken into consideration: material must be collected by groups which are formally authorized to do so and under the conditions of the Convention of Biological Diversity, the discovery process is being successively outsourced to smaller specialized firms and there is a growing integration with producers of cosmetics and phytomedicines.O uso de produtos extraídos de plantas para fins medicinais pode ser tracejado aos inícios da civilização e até o fim do século XIX, os produtos naturais constituíram a principal fonte de medicamentos. Desde então, a importância relativa dos produtos naturais tem oscilado de acordo com as estratégias de grandes companhias farmacêuticas. Agora que estas estratégias vêm mudando, há novas oportunidades para países como o Brasil, no qual está localizada uma vasta proporção da biodiversidade mundial. Há, entretanto, novas circunstâncias que devem ser levadas em consideração: o material deve ser coletado por grupos que estão formalmente autorizados para tal, com a coleta sendo feita sob as condições da Convenção de Diversidade Biológica, o processo de descoberta está sendo sucessivamente terceirizado no sentido de firmas especializadas menores e há uma integração crescente como produtores de cosméticos e fitomedicamentos.

  3. Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.

    Science.gov (United States)

    Gubbens, Jacob; Zhu, Hua; Girard, Geneviève; Song, Lijiang; Florea, Bogdan I; Aston, Philip; Ichinose, Koji; Filippov, Dmitri V; Choi, Young H; Overkleeft, Herman S; Challis, Gregory L; van Wezel, Gilles P

    2014-06-19

    Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters.

  4. Capital productivity and the nature of competition

    OpenAIRE

    Börsch-Supan, Axel

    1997-01-01

    This paper measures capital productivity in West Germany, Japan and the United States and links capital productivity to financial performance. We show that West Germany and Japan have significantly lower levels of capital productivity than the United States, mainly due to lower capital utilization but also because less productive capacity was created per unit of physical assets. On a higher level of causality, we show that this mainly comes from less pressure from product market competition a...

  5. Role of natural product diversity in chemical biology.

    Science.gov (United States)

    Hong, Jiyong

    2011-06-01

    Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products have demonstrated enormous potential as modulators of biomolecular function, been an essential source for drug discovery, and provided design principles for combinatorial library development.

  6. Natural Product Biosynthetic Diversity and Comparative Genomics of the Cyanobacteria.

    Science.gov (United States)

    Dittmann, Elke; Gugger, Muriel; Sivonen, Kaarina; Fewer, David P

    2015-10-01

    Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with intricate chemical structures and potent biological activities. The bulk of these natural products are known from just a handful of genera. Recent efforts have elucidated the mechanisms underpinning the biosynthesis of a diverse array of natural products from cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or rarely described from other organisms. Advances in genome sequence technology have precipitated a deluge of genome sequences for cyanobacteria. This makes it possible to link known natural products to biosynthetic gene clusters but also accelerates the discovery of new natural products through genome mining. These studies demonstrate that cyanobacteria encode a huge variety of cryptic gene clusters for the production of natural products, and the known chemical diversity is likely to be just a fraction of the true biosynthetic capabilities of this fascinating and ancient group of organisms.

  7. Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

    Science.gov (United States)

    Liu, Xiaonan; Ding, Wentao; Jiang, Huifeng

    2017-07-19

    Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

  8. Industrial natural product chemistry for drug discovery and development.

    Science.gov (United States)

    Bauer, Armin; Brönstrup, Mark

    2014-01-01

    Covering: up to March 2013. In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

  9. The chemistry and biology of guanidine natural products.

    Science.gov (United States)

    Berlinck, Roberto G S; Romminger, Stelamar

    2016-03-01

    The present review discusses the isolation, structure determination, synthesis, biosynthesis and biological activities of secondary metabolites bearing a guanidine group. Topics include non-ribosomal peptides, alkaloids, guanidine-bearing terpenes, polyketides and shikimic acid derivatives from natural sources. A critical analysis of some yet underdeveloped aspects of guanidine metabolites is also presented.

  10. Biosynthesis of therapeutic natural products using synthetic biology.

    Science.gov (United States)

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Natural health products and cancer chemotherapy and radiation therapy

    Directory of Open Access Journals (Sweden)

    Doreen Oneschuk

    2011-12-01

    Full Text Available Complementary therapies, notably natural health products such as herbs and vitamins, are frequently used by cancer patients receiving chemotherapy and radiation therapy. There is much controversy as to whether these natural health products should be taken during conventional cancer treatments. Supporters of this practice cite beneficial effects of the antioxidant properties, while opponents are concerned about the potential for natural health product-chemotherapy/radiation related negative interactions. This involves understanding the role and effect on metabolizing enzymes. This review will highlight the present evidence for both the beneficial and negative consequences of the use of natural health products during chemotherapy and radiation therapy.

  12. An overview of the marine natural products in clinical trials and on the market

    Directory of Open Access Journals (Sweden)

    Marisa Rangel

    2015-06-01

    Full Text Available The first marine natural products that served as leads or scaffolds for medicines were discovered in the middle of last century: the arabinosyl glycosides from the marine sponge Tectitethya crypta. Synthesis and modifications of the natural molecules generated antiviral and antileukemic drugs developed in the 1970’s and in the following decades, including the first effective treatment against HIV infection. With the improvement of techniques for the elucidation of chemical structure of the molecules, as well as chemical synthesis, especially from the 1990’s, there was an increase in the number of bioactive natural products characterized from marine organisms. New chemical structures with high specificity towards molecular targets in cells allowed the development of new drugs with indication for the treatment of several illnesses, from cancer to new antibiotics, and even neurological disorders. Currently there are at least 13 molecules derived from marine natural products on advanced clinical trials, and nine were approved to be used as medicines. Considering that in the past eight years, more than 1000 new compounds from marine organisms were described, per year, the expectation is that many more drugs will be derived from marine natural products in a near future.

  13. An overview of the marine natural products in clinical trials and on the market

    Institute of Scientific and Technical Information of China (English)

    Marisa Rangel; Miriam Falkenberg

    2015-01-01

    The first marine natural products that served as leads or scaffolds for medicines were discovered in the middle of last century:the arabinosyl glycosides from the marine sponge Tectitethya crypta. Synthesis and modifications of the natural molecules generated antiviral and antileukemic drugs developed in the 1970’s and in the following decades, including the first effective treatment against HIV infection. With the improvement of techniques for the elucidation of chemical structure of the molecules, as well as chemical synthesis, especially from the 1990’s, there was an increase in the number of bioactive natural products characterized from marine organisms. New chemical structures with high specificity towards molecular targets in cells allowed the development of new drugs with indication for the treatment of several illnesses, from cancer to new antibiotics, and even neurological disorders. Currently there are at least 13 molecules derived from marine natural products on advanced clinical trials, and nine were approved to be used as medicines. Considering that in the past eight years, more than 1 000 new compounds from marine organisms were described, per year, the expectation is that many more drugs will be derived from marine natural products in a near future.

  14. Supervisory controller synthesis for product lines using CIF 3

    NARCIS (Netherlands)

    M.H. ter Beek (Maurice); M.A. Reniers (Michel); E.P. de Vink (Erik Peter)

    2016-01-01

    textabstractUsing the CIF 3 toolset, we illustrate the general idea of controller synthesis for product line engineering for a prototypical example of a family of coffee machines. The challenge is to integrate a number of given components into a family of products such that the resulting behaviour

  15. Autothermal Reforming of Natural Gas to Synthesis Gas

    Energy Technology Data Exchange (ETDEWEB)

    Steven F. Rice; David P. Mann

    2007-04-13

    This Project Final Report serves to document the project structure and technical results achieved during the 3-year project titled Advanced Autothermal Reformer for US Dept of Energy Office of Industrial Technology. The project was initiated in December 2001 and was completed March 2005. It was a joint effort between Sandia National Laboratories (Livermore, CA), Kellogg Brown & Root LLC (KBR) (Houston, TX) and Süd-Chemie (Louisville, KY). The purpose of the project was to develop an experimental capability that could be used to examine the propensity for soot production in an Autothermal Reformer (ATR) during the production of hydrogen-carbon monoxide synthesis gas intended for Gas-to-Liquids (GTL) applications including ammonia, methanol, and higher hydrocarbons. The project consisted of an initial phase that was focused on developing a laboratory-scale ATR capable of reproducing conditions very similar to a plant scale unit. Due to budget constraints this effort was stopped at the advanced design stages, yielding a careful and detailed design for such a system including ATR vessel design, design of ancillary feed and let down units as well as a PI&D for laboratory installation. The experimental effort was then focused on a series of measurements to evaluate rich, high-pressure burner behavior at pressures as high as 500 psi. The soot formation measurements were based on laser attenuation at a view port downstream of the burner. The results of these experiments and accompanying calculations show that soot formation is primarily dependent on oxidation stoichiometry. However, steam to carbon ratio was found to impact soot production as well as burner stability. The data also showed that raising the operating pressure while holding mass flow rates constant results in considerable soot formation at desirable feed ratios. Elementary reaction modeling designed to illuminate the role of CO2 in the burner feed showed that the conditions in the burner allow for the direct

  16. Autothermal Reforming of Natural Gas to Synthesis Gas

    Energy Technology Data Exchange (ETDEWEB)

    Steven F. Rice; David P. Mann

    2007-04-13

    This Project Final Report serves to document the project structure and technical results achieved during the 3-year project titled Advanced Autothermal Reformer for US Dept of Energy Office of Industrial Technology. The project was initiated in December 2001 and was completed March 2005. It was a joint effort between Sandia National Laboratories (Livermore, CA), Kellogg Brown & Root LLC (KBR) (Houston, TX) and Süd-Chemie (Louisville, KY). The purpose of the project was to develop an experimental capability that could be used to examine the propensity for soot production in an Autothermal Reformer (ATR) during the production of hydrogen-carbon monoxide synthesis gas intended for Gas-to-Liquids (GTL) applications including ammonia, methanol, and higher hydrocarbons. The project consisted of an initial phase that was focused on developing a laboratory-scale ATR capable of reproducing conditions very similar to a plant scale unit. Due to budget constraints this effort was stopped at the advanced design stages, yielding a careful and detailed design for such a system including ATR vessel design, design of ancillary feed and let down units as well as a PI&D for laboratory installation. The experimental effort was then focused on a series of measurements to evaluate rich, high-pressure burner behavior at pressures as high as 500 psi. The soot formation measurements were based on laser attenuation at a view port downstream of the burner. The results of these experiments and accompanying calculations show that soot formation is primarily dependent on oxidation stoichiometry. However, steam to carbon ratio was found to impact soot production as well as burner stability. The data also showed that raising the operating pressure while holding mass flow rates constant results in considerable soot formation at desirable feed ratios. Elementary reaction modeling designed to illuminate the role of CO2 in the burner feed showed that the conditions in the burner allow for the direct

  17. Software Synthesis for High Productivity Exascale Computing

    Energy Technology Data Exchange (ETDEWEB)

    Bodik, Rastislav [Univ. of Washington, Seattle, WA (United States)

    2010-09-01

    Over the three years of our project, we accomplished three key milestones: We demonstrated how ideas from generative programming and software synthesis can help support the development of bulk-synchronous distributed memory kernels. These ideas are realized in a new language called MSL, a C-like language that combines synthesis features with high level notations for array manipulation and bulk-synchronous parallelism to simplify the semantic analysis required for synthesis. We also demonstrated that these high level notations map easily to low level C code and show that the performance of this generated code matches that of handwritten Fortran. Second, we introduced the idea of solver-aided domain-specific languages (SDSLs), which are an emerging class of computer-aided programming systems. SDSLs ease the construction of programs by automating tasks such as verification, debugging, synthesis, and non-deterministic execution. SDSLs are implemented by translating the DSL program into logical constraints. Next, we developed a symbolic virtual machine called Rosette, which simplifies the construction of such SDSLs and their compilers. We have used Rosette to build SynthCL, a subset of OpenCL that supports synthesis. Third, we developed novel numeric algorithms that move as little data as possible, either between levels of a memory hierarchy or between parallel processors over a network. We achieved progress in three aspects of this problem. First we determined lower bounds on communication. Second, we compared these lower bounds to widely used versions of these algorithms, and noted that these widely used algorithms usually communicate asymptotically more than is necessary. Third, we identified or invented new algorithms for most linear algebra problems that do attain these lower bounds, and demonstrated large speed-ups in theory and practice.

  18. Production of "Green Natural Gas" Using Solid Oxide Electrolysis Cells (SOEC): Status of Technology and Costs

    DEFF Research Database (Denmark)

    Mogensen, Mogens Bjerg; Jensen, Søren Højgaard; Ebbesen, Sune Dalgaard

    2012-01-01

    This paper gives arguments in favour of using green natural gas (GNG) as storage media for the intermittent renewable energy sources. GNG is here defined as being CH4, i.e. methane, often called synthetic natural gas or substitute natural gas (SNG), produced using renewable or at least CO2 neutral...... energy sources only. Also dimethyl ether (DME = (CH3)2O), which might be called Liquefied Green Gas, LGG, in analogy to Liquefied Petroleum Gas, LPG, because DME has properties similar to LPG. It further gives a short review of the state of the art of electrolysis in general and SOEC in particular....... Production of synthesis gas (H2 + CO) from CO2 and H2O using SOEC technology is evaluated. GNG and LGG can be produced from synthesis gas (or short: syngas) by means of well established commercially available catalysis technology. Finally, estimations of costs and efficiencies are presented and the relative...

  19. Scouring Process of Natural Color Cotton Products

    Institute of Scientific and Technical Information of China (English)

    XU Wei

    2002-01-01

    In order to improve the absorbency of color cotton products, alkali and pectase scouring processes under different conditions were tested, by comparing the actual results of two different scouring processes. It was considered that the pectase scouring process more suits color cotton products.

  20. Poly(ADP-ribose)--a unique natural polymer structural features, biological role and approaches to the chemical synthesis.

    Science.gov (United States)

    Drenichev, Mikhail S; Mikhailov, Sergey N

    2015-01-01

    Poly(ADP-ribose) (PAR) is a natural polymer, taking part in numerous important cellular processes. Several enzymes are involved in biosynthesis and degradation of PAR. One of them, poly(ADP-ribose)polymerase-1 (PARP-1) is considered to be a perspective target for the design of new drugs, affecting PAR metabolism. The structure of PAR was established by enzymatic hydrolysis and further analysis of the products, but total chemical synthesis of PAR hasn't been described yet. Several approaches have been developed on the way to chemical synthesis of this unique biopolymer.

  1. The challenges and opportunities for integration of solar syngas production with liquid fuel synthesis

    Science.gov (United States)

    Hinkley, James T.; McNaughton, Robbie K.; Pye, John; Saw, Woei; Stechel, Ellen B.

    2016-05-01

    Reforming of methane is practiced on a vast scale globally for the production of syngas as a precursor for the production of many commodities, including hydrogen, ammonia and synthetic liquid fuels. Solar reforming can reduce the greenhouse gas intensity of syngas production by up to about 40% by using solar thermal energy to provide the endothermic heat of reaction, traditionally supplied by combustion of some of the feed. This has the potential to enable the production of solar derived synthetic fuels as drop in replacements for conventional fuels with significantly lower CO2 intensity than conventional gas to liquids (GTL) processes. However, the intermittent nature of the solar resource - both diurnal and seasonal - poses significant challenges for such a concept, which relies on synthesis processes that typically run continuously on very stable feed compositions. We find that the integration of solar syngas production to a GTL process is a non-trivial exercise, with the ability to turn down the capacity of the GTL synthesis section, and indeed to suspend operations for short periods without significant detriment to product quality or process operability, likely to be a key driver for the commercial implementation of solar liquid fuels. Projected costs for liquid fuel synthesis suggest that solar reforming and small scale gas to liquid synthesis can potentially compete with conventional oil derived transport fuels in the short to medium term.

  2. Catharanthus roseus:a natural source for the synthesis of silver nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Mukunthan KS; Elumalai EK; Trupti N Patel; V Ramachandra Murty

    2011-01-01

    Objective: To develop a simple rapid procedure for bioreduction of silver nanoparticles (AgNPs) using aqueous leaves extracts of Catharanthus roseus (C. roseus). Methods: Characterization were determined by using UV-Vis spectrophotometry, scanning electron microscopy (SEM), energy dispersive X-ray and X-ray diffraction. Results: SEM showed the formation of silver nanoparticles with an average size of 67 nm to 48 nm. X-ray diffraction analysis showed that the particles were crystalline in nature with face centered cubic geometry. Conclusions: C. roseus demonstrates strong potential for synthesis of silver nanoparticles by rapid reduction of silver ions (Ag+ to Ag0). This study provides evidence for developing large scale commercial production of value-added products for biomedical/nanotechnology-based industries.

  3. Synthesis of anatase and rutile TiO{sub 2} nanostructures from natural ilmenite

    Energy Technology Data Exchange (ETDEWEB)

    Wahyuingsih, Sayekti, E-mail: sayekti@mipa.uns.ac.id; Ramelan, Ari Handono; Pramono, Edi; Sulistya, Ariantama Djati; Argawan, Panji Rofa; Dharmawan, Frenandha Dwi; Rinawati, Ludfiaastu; Hanif, Qonita Awliya [Inorganic Materials Research Group, Faculty of Mathematic and Natural Science, Sebelas Maret University (Indonesia); Sulistiyono, Eko; Firdiyono, Florentinus [Metallurgy Extraction Laboratory, Central of Metallurgy Research LIPI, Serpong (Indonesia)

    2016-02-08

    Nanostructure anatase and rutile type TiO{sub 2} were synthesized from dissolution roasted ilmenite from natural ilmenite sand as the starting materials. Anatase TiO{sub 2} and rutile TiO{sub 2} (high crystallinity) with the diameters of 20–100 nm were obtained by calcined soluble ilmenite sand produced by leaching process. Calcinations of the xerogel TiO{sub 2} from liquor products were conducted for 4 hours at temperature of 450 °C. The samples were characterized by XRD (X-ray diffraction), STA (simultant thermal analysis), TEM (Transmission Electron Microscopy), and BET surface area. Titania Anatase-Rutile form as a mixture were produced by titania slag with the hydrolysis product. While, in another route, complete titania anatase phase was produced through hydrolysis and condensation steps of leach liquors. This synthesis methods provide a simple route to fabricate nanostructure TiO{sub 2} from low cost material.

  4. Synthesis of anatase and rutile TiO2 nanostructures from natural ilmenite

    Science.gov (United States)

    Wahyuingsih, Sayekti; Ramelan, Ari Handono; Pramono, Edi; Sulistya, Ariantama Djati; Argawan, Panji Rofa; Dharmawan, Frenandha Dwi; Rinawati, Ludfiaastu; Hanif, Qonita Awliya; Sulistiyono, Eko; Firdiyono, Florentinus

    2016-02-01

    Nanostructure anatase and rutile type TiO2 were synthesized from dissolution roasted ilmenite from natural ilmenite sand as the starting materials. Anatase TiO2 and rutile TiO2 (high crystallinity) with the diameters of 20-100 nm were obtained by calcined soluble ilmenite sand produced by leaching process. Calcinations of the xerogel TiO2 from liquor products were conducted for 4 hours at temperature of 450 °C. The samples were characterized by XRD (X-ray diffraction), STA (simultant thermal analysis), TEM (Transmission Electron Microscopy), and BET surface area. Titania Anatase-Rutile form as a mixture were produced by titania slag with the hydrolysis product. While, in another route, complete titania anatase phase was produced through hydrolysis and condensation steps of leach liquors. This synthesis methods provide a simple route to fabricate nanostructure TiO2 from low cost material.

  5. Generation of synthesis gas by partial oxidation of natural gas in a gas turbine

    NARCIS (Netherlands)

    Cornelissen, R.; Tober, E.; Kok, J.B.W.; Meer, van der T.H.

    2006-01-01

    The application of partial oxidation in a gas turbine (PO-GT) in the production of synthesis gas for methanol production is explored. In PO-GT, methane is compressed, preheated, partial oxidized and expanded. For the methanol synthesis a 12% gain in thermal efficiency has been calculated for the PO-

  6. Generation of synthesis gas by partial oxidation of natural gas in a gas turbine

    NARCIS (Netherlands)

    Cornelissen, R.; Tober, E.; Kok, Jacobus B.W.; van der Meer, Theodorus H.

    2006-01-01

    The application of partial oxidation in a gas turbine (PO-GT) in the production of synthesis gas for methanol production is explored. In PO-GT, methane is compressed, preheated, partial oxidized and expanded. For the methanol synthesis a 12% gain in thermal efficiency has been calculated for the

  7. Bioactive natural products in cancer prevention and therapy: Progress and promise.

    Science.gov (United States)

    Bishayee, Anupam; Sethi, Gautam

    2016-10-01

    Natural products represent a rich source for the discovery and development of cancer preventive and anticancer drugs. Nearly, 80% of all drugs approved by the United States Food and Drug Administration during the last three decades for cancer therapy are either natural products per se or are based thereon, or mimicked natural products in one form or another. With the advent and refinement of new technologies, such as genetic techniques for production of secondary plant metabolites, combinatorial synthesis and high-throughput screening, it is expected that novel compounds from natural sources, including medicinal plants, would be identified and developed as safe and effective chemopreventive and anticancer drugs. Numerous bioactive natural compounds have been shown to be useful in prevention and therapy of cancer by targeting various signaling molecules and pathways. Extensive literature underscores the anticancer and chemopreventive activity of a plethora of naturally occurring agents, including phytochemicals. Several of these molecules have been tested in clinical trials and some of them have shown promise in combination therapy when administered along with standard chemotherapeutic agents. Thus, accelerated chemopreventive and chemotherapeutic drug development from natural sources is of great importance. In this special theme issue, contributions from eminent scientists and scholars around the world presented critical analysis of the current progress and promise of natural bioactive constituents in cancer prevention and therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. New natural products as new leads for antibacterial drug discovery.

    Science.gov (United States)

    Brown, Dean G; Lister, Troy; May-Dracka, Tricia L

    2014-01-15

    Natural products have been a rich source of antibacterial drugs for many decades, but investments in this area have declined over the past two decades. The purpose of this review article is to provide a recent survey of new natural product classes and the mechanisms by which they work.

  9. Rapid Growth in China Natural Gas Demand and Production

    Institute of Scientific and Technical Information of China (English)

    Li Min

    2003-01-01

    @@ China's natural gas production will exceed 35 billion cubic meters in 2003,more than 7 percent up from last year,according to the estimation by the related department. There are now more than 60 enterprises engaged in natural gas production in China.

  10. China Ranks 15th for 2001 Natural Gas Production

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ China's natural gas output totaled 30.302 billion cubic meters in 2001, an 11 percent increase as compared with the previous year. However, China ranked 15th in the world for its natural gas production last year while Malaysia jumped to the 12th place in the ranking since the country saw a considerable increase in gas production.

  11. Psychoactive natural products: overview of recent developments

    OpenAIRE

    2014-01-01

    Natural psychoactive substances have fascinated the curious mind of shamans, artists, scholars and laymen since antiquity. During the twentieth century, the chemical composition of the most important psychoactive drugs, that is opium, cannabis, coca and "magic mushrooms", has been fully elucidated. The mode of action of the principal ingredients has also been deciphered at the molecular level. In the past two decades, the use of herbal drugs, such as kava, kratom and Salvia divinorum, began t...

  12. Recent Advances in Separation of Bioactive Natural Products

    Institute of Scientific and Technical Information of China (English)

    任其龙; 邢华斌; 鲍宗必; 苏宝根; 杨启炜; 杨亦文; 张治国

    2013-01-01

    Bioactive natural products are a main source of new drugs, functional foods and food additives. The separation of bioactive natural products plays an important role in transformation and use of biomass. The isolation and purification of bioactive principle from a complex matrix is often inherent bottleneck for the utilization of natural products, so a series of extraction and separation techniques have been developed. This review covers recent advances in the separation of bioactive natural products with an emphasis on their solubility and diffusion coeffi-cients, recent extraction techniques and isolation techniques. This overview of recent technological advances, dis-cussion of pertinent problems and prospect of current methodologies in the separation of bioactive natural products may provide a driving force for development of novel separation techniques.

  13. Bioactive natural products from Papua New Guinea marine sponges.

    Science.gov (United States)

    Noro, Jeffery C; Kalaitzis, John A; Neilan, Brett A

    2012-10-01

    The discovery of novel natural products for drug development relies heavily upon a rich biodiversity, of which the marine environment is an obvious example. Marine natural product research has spawned several drugs and many other candidates, some of which are the focus of current clinical trials. The sponge megadiversity of Papua New Guinea is a rich but underexplored source of bioactive natural products. Here, we review some of the many natural products derived from PNG sponges with an emphasis on those with interesting biological activity and, therefore, drug potential. Many bioactive natural products discussed here appear to be derived from non-ribosomal peptide and polyketide biosynthesis pathways, strongly suggesting a microbial origin of these compounds. With this in mind, we also explore the notion of sponge-symbiont biosynthesis of these bioactive compounds and present examples to support the working hypothesis.

  14. Marinopyrroles: Unique Drug Discoveries Based on Marine Natural Products.

    Science.gov (United States)

    Li, Rongshi

    2016-01-01

    Natural products provide a successful supply of new chemical entities (NCEs) for drug discovery to treat human diseases. Approximately half of the NCEs are based on natural products and their derivatives. Notably, marine natural products, a largely untapped resource, have contributed to drug discovery and development with eight drugs or cosmeceuticals approved by the U.S. Food and Drug Administration and European Medicines Agency, and ten candidates undergoing clinical trials. Collaborative efforts from drug developers, biologists, organic, medicinal, and natural product chemists have elevated drug discoveries to new levels. These efforts are expected to continue to improve the efficiency of natural product-based drugs. Marinopyrroles are examined here as a case study for potential anticancer and antibiotic agents.

  15. Natural Products Version 2.0: Connecting Genes to Molecules

    Science.gov (United States)

    Walsh, Christopher T.; Fischbach, Michael A.

    2009-01-01

    Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this perspective, we explore how connecting Nature’s small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and nonribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future? PMID:20121095

  16. Antimycobacterial susceptibility testing methods for natural products research

    Directory of Open Access Journals (Sweden)

    Juan Gabriel Bueno Sánchez

    2010-06-01

    Full Text Available The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need of continuous developments on new and efficient methods to determine the susceptibility of isolates of M. tuberculosis in the search for novel antimicrobial agents. Natural products constitute an important source of new drugs, but design and implementation of antimycobacterial susceptibility testing methods are necessary for evaluate the different extracts and compounds. A number of biological assay methodologies are in current use, ranging from the classical disk diffusion and broth dilution assay format, to radiorespirometric (BACTEC, dye-based, and fluorescent/luminescence reporter assays. This review presents an analysis on the in vitro susceptibility testing methods developed for determinate antitubercular activity in natural products and related compounds (semi-synthetic natural products and natural products-derived compounds and the criteria to select the adequate method for determination of biological activity of new natural products.

  17. MARINE NATURAL PRODUCTS: A WAY TO NEW DRUGS

    OpenAIRE

    Stonik, V.

    2009-01-01

    The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural...

  18. Marine actinobacteria: new opportunities for natural product search and discovery.

    Science.gov (United States)

    Bull, Alan T; Stach, James E M

    2007-11-01

    It is widely accepted that new drugs, especially antibiotics, are urgently required, and that the most propitious source remains natural products. We argue that in exploring new sources of bioactive natural products the marine environment warrants particular attention, in view of the remarkable diversity of microorganisms and metabolic products. Recent reports of new chemical entities and first-in-class drug candidates, and confirmation of indigenous marine actinobacteria, make exciting discoveries even more likely given the unrivalled capacity of this class of bacteria to produce exploitable natural products.

  19. The structural biology of enzymes involved in natural product glycosylation.

    Science.gov (United States)

    Singh, Shanteri; Phillips, George N; Thorson, Jon S

    2012-10-01

    The glycosylation of microbial natural products often dramatically influences the biological and/or pharmacological activities of the parental metabolite. Over the past decade, crystal structures of several enzymes involved in the biosynthesis and attachment of novel sugars found appended to natural products have emerged. In many cases, these studies have paved the way to a better understanding of the corresponding enzyme mechanism of action and have served as a starting point for engineering variant enzymes to facilitate to production of differentially-glycosylated natural products. This review specifically summarizes the structural studies of bacterial enzymes involved in biosynthesis of novel sugar nucleotides.

  20. Design, Synthesis and Trypanocidal Evaluation of Novel 1,2,4-Triazoles-3-thiones Derived from Natural Piperine

    Directory of Open Access Journals (Sweden)

    Marco Edilson Freire de Lima

    2013-05-01

    Full Text Available The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The variously substituted triazole derivatives were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain, with IC50s = 18.3 and 8.87 mM against epimastigotes and amastigotes, respectively.

  1. Temperature oscillations near natural nuclear reactor cores and the potential for prebiotic oligomer synthesis.

    Science.gov (United States)

    Adam, Zachary R

    2016-06-01

    Geologic settings capable of driving prebiotic oligomer synthesis reactions remain a relatively unexplored aspect of origins of life research. Natural nuclear reactors are an example of Precambrian energy sources that produced unique temperature fluctuations. Heat transfer models indicate that water-moderated, convectively-cooled natural fission reactors in porous host rocks create temperature oscillations that resemble those employed in polymerase chain reaction (PCR) devices to artificially amplify oligonucleotides. This temperature profile is characterized by short-duration pulses up to 70-100 °C, followed by a sustained period of temperatures in the range of 30-70 °C, and finally a period of relaxation to ambient temperatures until the cycle is restarted by a fresh influx of pore water. For a given reactor configuration, temperature maxima and the time required to relax to ambient temperatures depend most strongly on the aggregate effect of host rock permeability in decreasing the thermal expansion and increasing the viscosity and evaporation temperature of the pore fluids. Once formed, fission-fueled reactors can sustain multi-kilowatt-level power production for 10(5)-10(6) years, ensuring microenvironmental longevity and chemical output. The model outputs indicate that organic synthesis on young planetary bodies with a sizeable reservoir of fissile material can involve more sophisticated energy dissipation pathways than modern terrestrial analog settings alone would suggest.

  2. Temperature oscillations near natural nuclear reactor cores and the potential for prebiotic oligomer synthesis

    Science.gov (United States)

    Adam, Zachary R.

    2016-06-01

    Geologic settings capable of driving prebiotic oligomer synthesis reactions remain a relatively unexplored aspect of origins of life research. Natural nuclear reactors are an example of Precambrian energy sources that produced unique temperature fluctuations. Heat transfer models indicate that water-moderated, convectively-cooled natural fission reactors in porous host rocks create temperature oscillations that resemble those employed in polymerase chain reaction (PCR) devices to artificially amplify oligonucleotides. This temperature profile is characterized by short-duration pulses up to 70-100 °C, followed by a sustained period of temperatures in the range of 30-70 °C, and finally a period of relaxation to ambient temperatures until the cycle is restarted by a fresh influx of pore water. For a given reactor configuration, temperature maxima and the time required to relax to ambient temperatures depend most strongly on the aggregate effect of host rock permeability in decreasing the thermal expansion and increasing the viscosity and evaporation temperature of the pore fluids. Once formed, fission-fueled reactors can sustain multi-kilowatt-level power production for 105-106 years, ensuring microenvironmental longevity and chemical output. The model outputs indicate that organic synthesis on young planetary bodies with a sizeable reservoir of fissile material can involve more sophisticated energy dissipation pathways than modern terrestrial analog settings alone would suggest.

  3. Strategies for target identification of antimicrobial natural products.

    Science.gov (United States)

    Farha, Maya A; Brown, Eric D

    2016-05-04

    Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

  4. Specific Nature of Application of Various Carbon Components for Mechanochemical Synthesis of Titanium Carbide

    Science.gov (United States)

    Reva, V. P.; Yagofarov, V. U.; Gulevskii, D. A.; Filatenkov, A. E.; Mansurov, Yu N.

    2016-08-01

    It has been established that structure of carbon modifications, obtained via pyrolysis of vegetable feed, and ash content of natural graphite are crucial factors during mechanochemical synthesis of titanium carbide under vibratory conditions. The possibility of synthesis of titanium carbide with minimal sulfur content has been shown.

  5. NATURAL ANTIOXIDANTS IN PRODUCTION “BRUSHWOOD”

    Directory of Open Access Journals (Sweden)

    G. N. Dubtsova

    2015-01-01

    Full Text Available Flour wares use popularity, there is 48% of general volume of pastry wares on their stake. A marketing study on results that actuality of development of new type of flour good is set with the lowered maintenance of fat and enriched by vitamins is undertaken. The use of natural antioxidant of "Guarding is reasonable toco 70" and introduction of 0,2% is recommended for stabilizing of sunflower-seed oil at fry of frying. Joint introduction of powders is studied from the garden-stuffs of brier and unabi on quality of the brushwood fried in sunflower-seed oil with the use of "Guarding toco 70". From wares extracted lipids and estimated on indexes: peroxides, acid and anizid numbers. It is set that an antioxidant and vegetable powders assist the decline of indexes of safety peroxides and asid in two times, and anizid in 1,3 time. Use of antioxidant of "Guarding toco 70", being in 70% from the natural concentrate of mixture of tocopherolss and 30% of soyaoil.

  6. Chemo- and site-selective derivatizations of natural products enabling biological studies.

    Science.gov (United States)

    Robles, Omar; Romo, Daniel

    2014-03-01

    Bioactive natural products and derivatives remain an enduring starting point for the discovery of new cellular targets for disease intervention and lead compounds for the development of new therapeutic agents. The former goal is accomplished through the synthesis of bioactive cellular probes from natural products, enabling insights into the mechanism of action of these natural products by classical affinity chromatography or more recent proteome profiling methods. However, the direct and selective modification of native natural products for these purposes remains a challenge due to the structural complexity and the wide functional group diversity found in these natural substances. The lack of selective synthetic methods available to directly manipulate unprotected complex small molecules, in particular to perform structure-activity relationship studies and prepare appropriate cellular probes, has recently begun to be addressed, benefitting from the broader emerging area of chemoselective synthetic methodology. Thus, new reagents, catalysts and reaction processes are enabling both chemo- and site-selective modifications of complex, native natural products. In this review, we describe selected recent examples of these functionalization strategies in this emerging area.

  7. Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B

    Directory of Open Access Journals (Sweden)

    Jacquie L. Harper

    2015-08-01

    Full Text Available In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds.

  8. Chemical Biology of Microbial Anticancer Natural Products

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Gotfredsen, Charlotte Held

    towards chronic lymphocytic leukemia (CLL) cells is crucial since CLL is considered as an incurable disease. To discover novel agents that targets CLL cells is complicated. CLL cells rapidly undergo apoptosis in vitro when they are removed from their natural microenvironment, even though they are long......Filamentous fungi and other microorganisms have amazing abilities to synthesize structural complex, diverse and unique small organic molecules. Many are bioactive and numerous compounds such as mycotoxins, antifungal, and anticancer agents have been reported in the literature within the last more......-living cells in vivo. Fortunately viability of CLL cells can be maintained in vitro by co-cultivation with stromal cells mimicking in vivo conditions. This has led to the development of a co-culture assay that is ideally suited for screening of NPs. The main goal of this study has been to discover fungal NPs...

  9. Efficient Product Customization by Structure Synthesis

    OpenAIRE

    Maurer, M.;Rupp, T.;Lindemann, U.

    2017-01-01

    The presented approach describes a new strategy for creating product structures, which are suitable for further customer driven product customization – i.e. the customization can be carried out within less time and for lower costs. The required input data is knowledge on the interconnectivity between product components and knowledge of principal scopes of customization demands (e.g. which components or functions customers would like to individualize, which ones are unknown or hidden). By mean...

  10. College of Natural Resources to offer Forest Products Marketing Workshop

    OpenAIRE

    Davis, Lynn

    2008-01-01

    Marketing has been called the backbone of successful forest products companies, yet many small businesses struggle with the marketing concept. Virginia Tech's College of Natural Resources continues its service to the forest products industry by presenting the fourteenth annual workshop on Forest Products Marketing, Oct. 23 through Oct. 24, at The Inn at Virginia Tech and Skelton Conference Center.

  11. Separation process design for isolation and purification of natural products

    DEFF Research Database (Denmark)

    Malwade, Chandrakant R.

    Natural products are defined as secondary metabolites produced by plants and form a vast pool of compounds with unlimited chemical and functional diversity. Many of these secondary metabolites are high value added chemicals that are frequently used as ingredients in food, cosmetics, pharmaceutica...... information is used to further optimize the process flow sheet. Chemometric methods have been used to extract molecular level information for understanding the process streams in relation to their separation operations....... and other consumer products. Therefore, process technology towards industrial scale production of such high value chemicals from plants has significant value. Natural products can be obtained in pure form via synthetic or semi-synthetic route, but due to their complicated nature these methods have not been...... developed to the extent of industrial production for majority of natural products. Thus, isolation and purification of such natural products from plants is the most viable way to obtain natural products in pure form. This PhD project is mainly concerned with the design of separation process to isolate...

  12. Dereplication of Microbial Natural Products by LC-DAD-TOFMS

    DEFF Research Database (Denmark)

    Nielsen, Kristian Fog; Månsson, Maria; Rank, Christian;

    2011-01-01

    Dereplication, the rapid identification of known compounds present in a mixture, is crucial to the fast discovery of novel natural products. Determining the elemental composition of compounds in mixtures and tentatively identifying natural products using MS/MS and UV/vis spectra is becoming easier...... with advances in analytical equipment and better compound databases. Here we demonstrate the use of LC-UV/vis-MS-based dereplication using data from UV/vis diode array detection and ESI+/ESI– time-of-flight MS for assignment of 719 microbial natural product and mycotoxin reference standards. ESI+ was the most...

  13. Solid-phase enrichment and analysis of electrophilic natural products

    Directory of Open Access Journals (Sweden)

    Frank Wesche

    2017-03-01

    Full Text Available In search for new natural products, which may lead to the development of new drugs for all kind of applications, novel methods are needed. Here we describe the identification of electrophilic natural products in crude extracts via their reactivity against azide as a nucleophile followed by their subsequent enrichment using a cleavable azide-reactive resin (CARR. Using this approach, natural products carrying epoxides and α,β-unsaturated enones as well as several unknown compounds were identified in crude extracts from entomopathogenic Photorhabdus bacteria.

  14. Lactide Synthesis and Chirality Control for Polylactic acid Production.

    Science.gov (United States)

    Van Wouwe, Pieter; Dusselier, Michiel; Vanleeuw, Evelien; Sels, Bert

    2016-05-10

    Polylactic acid (PLA) is a very promising biodegradable, renewable, and biocompatible polymer. Aside from its production, its application field is also increasing, with use not only in commodity applications but also as durables and in biomedicine. In the current PLA production scheme, the most expensive part is not the polymerization itself but obtaining the building blocks lactic acid (LA) and lactide, the actual cyclic monomer for polymerization. Although the synthesis of LA and the polymerization have been studied systematically, reports of lactide synthesis are scarce. Most lactide synthesis methods are described in patent literature, and current energy-intensive, aselective industrial processes are based on archaic scientific literature. This Review, therefore, highlights new methods with a technical comparison and description of the different approaches. Water-removal methodologies are compared, as this is a crucial factor in PLA production. Apart from the synthesis of lactide, this Review also emphasizes the use of chemically produced racemic lactic acid (esters) as a starting point in the PLA production scheme. Stereochemically tailored PLA can be produced according to such a strategy, giving access to various polymer properties.

  15. Production of Substitute Natural Gas from Coal

    Energy Technology Data Exchange (ETDEWEB)

    Andrew Lucero

    2009-01-31

    The goal of this research program was to develop and demonstrate a novel gasification technology to produce substitute natural gas (SNG) from coal. The technology relies on a continuous sequential processing method that differs substantially from the historic methanation or hydro-gasification processing technologies. The thermo-chemistry relies on all the same reactions, but the processing sequences are different. The proposed concept is appropriate for western sub-bituminous coals, which tend to be composed of about half fixed carbon and about half volatile matter (dry ash-free basis). In the most general terms the process requires four steps (1) separating the fixed carbon from the volatile matter (pyrolysis); (2) converting the volatile fraction into syngas (reforming); (3) reacting the syngas with heated carbon to make methane-rich fuel gas (methanation and hydro-gasification); and (4) generating process heat by combusting residual char (combustion). A key feature of this technology is that no oxygen plant is needed for char combustion.

  16. Manufacturing Natural Killer Cells as Medicinal Products

    Science.gov (United States)

    Chabannon, Christian; Mfarrej, Bechara; Guia, Sophie; Ugolini, Sophie; Devillier, Raynier; Blaise, Didier; Vivier, Eric; Calmels, Boris

    2016-01-01

    Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers. NK cell activity can possibly be modulated in vivo through direct or indirect actions exerted by small molecules or monoclonal antibodies. NK cells can also be adoptively transferred following more or less substantial modifications through cell and gene manufacturing, in order to empower them with new or improved functions and ensure their controlled persistence and activity in the recipient. In the present review, we will focus on the technological and regulatory challenges of NK cell manufacturing and discuss conditions in which these innovative cellular therapies can be brought to the clinic. PMID:27895646

  17. Bioinformatics for the synthetic biology of natural products: integrating across the Design–Build–Test cycle

    Science.gov (United States)

    Currin, Andrew; Jervis, Adrian J.; Rattray, Nicholas J. W.; Swainston, Neil; Yan, Cunyu; Breitling, Rainer

    2016-01-01

    Covering: 2000 to 2016 Progress in synthetic biology is enabled by powerful bioinformatics tools allowing the integration of the design, build and test stages of the biological engineering cycle. In this review we illustrate how this integration can be achieved, with a particular focus on natural products discovery and production. Bioinformatics tools for the DESIGN and BUILD stages include tools for the selection, synthesis, assembly and optimization of parts (enzymes and regulatory elements), devices (pathways) and systems (chassis). TEST tools include those for screening, identification and quantification of metabolites for rapid prototyping. The main advantages and limitations of these tools as well as their interoperability capabilities are highlighted. PMID:27185383

  18. Opportunities for natural products in 21(st) century antibiotic discovery.

    Science.gov (United States)

    Wright, Gerard D

    2017-07-01

    Natural products and their derivatives are mainstays of our antibiotic drugs, but they are increasingly in peril. The combination of widespread multidrug resistance in once susceptible bacterial pathogens, disenchantment with natural products as sources of new drugs, lack of success using synthetic compounds and target-based discovery methods, along with shifting economic and regulatory issues, conspire to move investment in research and development away from the antibiotics arena. The result is a growing crisis in antibiotic drug discovery that threatens modern medicine. 21(st) century natural product research is perfectly positioned to fill the antibiotic discovery gap and bring new drug candidates to the clinic. Innovations in genomics and techniques to explore new sources of antimicrobial chemical matter are revealing new chemistry. Increasing appreciation of the value of narrow-spectrum drugs and re-examination of once discarded chemical scaffolds coupled with synthetic biology methods to generate new compounds and improve yields offer new strategies to revitalize once moribund natural product programs. The increasing awareness that the combination of antibiotics with adjuvants, non-antibiotic compounds that overcome resistance and enhance drug activity, can rescue older chemical scaffolds, and concepts such as blocking pathogen virulence present orthogonal strategies to traditional antibiotics. In all these areas, natural products offer chemical matter, shaped by natural selection, that is privileged in this therapeutic area. Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis.

  19. Raman spectra of carotenoids in natural products

    Science.gov (United States)

    Withnall, Robert; Chowdhry, Babur Z.; Silver, Jack; Edwards, Howell G. M.; de Oliveira, Luiz F. C.

    2003-08-01

    Resonance Raman spectra of naturally occurring carotenoids have been obtained from nautilus, periwinkle ( Littorina littorea) and clam shells under 514.5 nm excitation and these spectra are compared with the resonance Raman spectra obtained in situ from tomatoes, carrots, red peppers and saffron. The tomatoes, carrots and red peppers gave rise to resonance Raman spectra exhibiting a ν1 band at ca. 1520 cm -1, in keeping with its assignment to carotenoids with ca. nine conjugated carboncarbon double bonds in their main chains, whereas the resonance Raman spectrum of saffron showed a ν1 band at 1537 cm -1 which can be assigned to crocetin, having seven conjugated carboncarbon double bonds. A correlation between ν1 wavenumber location and effective conjugated chain length has been used to interpret the data obtained from the shells, and the wavenumber position (1522 cm -1) of the ν1 band of the carotenoid in the orange clam shell suggests that it contains nine conjugated double bonds in the main chain. However, the black periwinkle and nautilus shells exhibit ν1 bands at 1504 and 1496 cm -1, respectively. On the basis of the correlation between ν1 wavenumber location and effective conjugated chain length, this indicates that they contain carotenoids with longer conjugated chains, the former having ca. 11 double bonds and the latter ca. 13 or even more. Raman spectra of the nautilus, periwinkle and clam shells also exhibited a strong band at 1085 cm -1 and a doublet with components at 701 and 705 cm -1, which can be assigned to biogenic calcium carbonate in the aragonite crystallographic form.

  20. Natural and within-farmland biodiversity enhances crop productivity.

    Science.gov (United States)

    Carvalheiro, Luísa Gigante; Veldtman, Ruan; Shenkute, Awraris Getachew; Tesfay, Gebreamlak Bezabih; Pirk, Christian Walter Werner; Donaldson, John Sydney; Nicolson, Susan Wendy

    2011-03-01

    Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture.

  1. Reinvigorating natural product combinatorial biosynthesis with synthetic biology.

    Science.gov (United States)

    Kim, Eunji; Moore, Bradley S; Yoon, Yeo Joon

    2015-09-01

    Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis--altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes--offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.

  2. Natural Product Polyamines That Inhibit Human Carbonic Anhydrases

    Directory of Open Access Journals (Sweden)

    Rohan A. Davis

    2014-01-01

    Full Text Available Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs. CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines 1–5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines 1–5 were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.

  3. Does species diversity limit productivity in natural grassland communities?

    NARCIS (Netherlands)

    Grace, James B.; Anderson, T. Michael; Smith, Melinda D.; Seabloom, Eric; Andelman, Sandy J.; Meche, Gayna; Weiher, Evan; Allain, Larry K.; Jutila, Heli; Sankaran, Mahesh; Knops, Johannes; Ritchie, Mark; Willig, Michael R.

    2007-01-01

    Theoretical analyses and experimental studies of synthesized assemblages indicate that under particular circumstances species diversity can enhance community productivity through niche complementarity. It remains unclear whether this process has important effects in mature natural ecosystems where c

  4. Revealing the macromolecular targets of complex natural products

    Science.gov (United States)

    Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

  5. Does species diversity limit productivity in natural grassland communities?

    NARCIS (Netherlands)

    Grace, James B.; Anderson, T. Michael; Smith, Melinda D.; Seabloom, Eric; Andelman, Sandy J.; Meche, Gayna; Weiher, Evan; Allain, Larry K.; Jutila, Heli; Sankaran, Mahesh; Knops, Johannes; Ritchie, Mark; Willig, Michael R.

    Theoretical analyses and experimental studies of synthesized assemblages indicate that under particular circumstances species diversity can enhance community productivity through niche complementarity. It remains unclear whether this process has important effects in mature natural ecosystems where

  6. Nigerian Journal of Natural Products and Medicine - Vol 2 (1998)

    African Journals Online (AJOL)

    Nigerian Journal of Natural Products and Medicine - Vol 2 (1998) ... RESEARCH AND DEVELOPMENT INTO HERBAL MEDICINES · EMAIL FULL ... OF BRIDELIA FERRUGUBEA STEM BARK ON BLOOD CHEMISTRY AND HISTOLOGY OF ...

  7. Marine organisms: an alternative source of potentially valuable natural products

    Directory of Open Access Journals (Sweden)

    Alphonse Kelecom

    1991-01-01

    Full Text Available This paper recalls the outcoming of marine natural products research and reviews a selection of marirne bioactive metabolites in current use together with promising trends in marine pharmacology.

  8. Use of Brown Algae to Demonstrate Natural Products Techniques.

    Science.gov (United States)

    Porter, Lee A.

    1985-01-01

    Background information is provided on the natural products found in marine organisms in general and the brown algae in particular. Also provided are the procedures needed to isolate D-mannitol (a primary metabolite) and cholesterol from brown algae. (JN)

  9. Journals on Traditional Medicine and Natural Products Published in English

    Institute of Scientific and Technical Information of China (English)

    CONG Wei-hong; CHEN Ke-ji

    2010-01-01

    @@ Due to better understanding of traditional medicine, complementary and alternative medicine, and natural products, there are increasing findings in these fields.In order to facilitate the findings to be known widely and timely by readers, here this article showed researchers some journals on traditional medicine, complementary and alternative medicine,and natural products, published in English and tracked by Thomson Reuters (ISI) in 2009, as well as some influential journals untracked by ISI.

  10. Marine natural products sourced from marine-derived Penicillium fungi.

    Science.gov (United States)

    Ma, Hong-Guang; Liu, Qiang; Zhu, Guo-Liang; Liu, Hai-Shan; Zhu, Wei-Ming

    2016-01-01

    Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.

  11. Emerging trends in the discovery of natural product antibacterials

    DEFF Research Database (Denmark)

    Bologa, Cristian G; Ursu, Oleg; Oprea, Tudor;

    2013-01-01

    mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antibacterial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting bacterial phenotypes....... These efforts have identified a critical mass of natural product antibacterial lead compounds and discovery technologies with high probability of successful implementation against emerging bacterial pathogens....

  12. Anti-Enterovirus 71 Agents of Natural Products

    Directory of Open Access Journals (Sweden)

    Liyan Wang

    2015-09-01

    Full Text Available This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  13. Biotechnological production of natural zero-calorie sweeteners.

    Science.gov (United States)

    Philippe, Ryan N; De Mey, Marjan; Anderson, Jeff; Ajikumar, Parayil Kumaran

    2014-04-01

    The increasing public awareness of adverse health impacts from excessive sugar consumption has created increasing interest in plant-derived, natural low-calorie or zero-calorie sweeteners. Two plant species which contain natural sweeteners, Stevia rebaudiana and Siraitia grosvenorii, have been extensively profiled to identify molecules with high intensity sweetening properties. However, sweetening ability does not necessarily make a product viable for commercial applications. Some criteria for product success are proposed to identify which targets are likely to be accepted by consumers. Limitations of plant-based production are discussed, and a case is put forward for the necessity of biotechnological production methods such as plant cell culture or microbial fermentation to meet needs for commercial-scale production of natural sweeteners.

  14. 15 CFR 715.1 - Annual declaration requirements for production by synthesis of unscheduled discrete organic...

    Science.gov (United States)

    2010-01-01

    ... production by synthesis of unscheduled discrete organic chemicals (UDOCs). 715.1 Section 715.1 Commerce and... DISCRETE ORGANIC CHEMICALS (UDOCs) § 715.1 Annual declaration requirements for production by synthesis of unscheduled discrete organic chemicals (UDOCs). (a) Declaration of production by synthesis of UDOCs for...

  15. The sustainable management of a productive natural capital

    DEFF Research Database (Denmark)

    Daubanes, Julien Xavier

    This paper examines an industry whose economic activity uses a natural capital on which its profit also relies. When such a productive natural capital has a limited capacity to recover from its exploitation, a free market tends to over-exploit it, calling for public intervention. The analysis...... is relevant, among other examples, to the case of naturebased tourism. I study the sustainable management of a productive natural capital: the conditions under which its exploitation generates maximum long-run social benefits; the various ways in which a regulator can implement such an exploitation; the rent...

  16. Microgravity Production of Nanoparticles of Novel Materials Using Plasma Synthesis

    Science.gov (United States)

    Frenklach, Michael; Fernandez-Pello, Carlos

    2001-01-01

    The research goal is to study the formation in reduced gravity of high quality nanoparticulate of novel materials using plasma synthesis. Particular emphasis will be placed on the production of powders of non-oxide materials like diamond, SiC, SiN, c-BN, etc. The objective of the study is to investigate the effect of gravity on plasma synthesis of these materials, and to determine how the microgravity synthesis can improve the quality and yield of the nanoparticles. It is expected that the reduced gravity will aid in the understanding of the controlling mechanisms of plasma synthesis, and will increase the yield, and quality of the synthesized powder. These materials have properties of interest in several industrial applications, such as high temperature load bearings or high speed metal machining. Furthermore, because of the nano-meter size of the particulate produced in this process, they have specific application in the fabrication of MEMS based combustion systems, and in the development and growth of nano-systems and nano-structures of these materials. These are rapidly advancing research areas, and there is a great need for high quality nanoparticles of different materials. One of the primary systems of interest in the project will be gas-phase synthesis of nanopowder of non-oxide materials.

  17. Natural product biosynthesis: It's all downhill from here

    Science.gov (United States)

    Hornsby, Charles E.; Paton, Robert S.

    2014-02-01

    High selectivity is essential in the enzymatic biosynthesis of complex natural products. Now, the discovery of multiple sequential bifurcations on the reaction path towards the formation of a diterpenoid shows how dynamics affect selectivity, and suggests how enzymes may steer reactions towards a specific product.

  18. Nature-Inspired Design: Strategies for Sustainable Product Development

    NARCIS (Netherlands)

    De Pauw, I.C.

    2015-01-01

    Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing sustainability. Biomimic

  19. Nature-Inspired Design: Strategies for Sustainable Product Development

    NARCIS (Netherlands)

    De Pauw, I.C.

    2015-01-01

    Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing

  20. Nature-Inspired Design: Strategies for Sustainable Product Development

    NARCIS (Netherlands)

    De Pauw, I.C.

    2015-01-01

    Product designers can apply different strategies, methods, and tools for sustainable product development. Nature-Inspired Design Strategies (NIDS) offer designers a distinct class of strategies that use ‘nature’ as a guiding source of knowledge and inspiration for addressing sustainability. Biomimic

  1. Natural product-inspired rational design, synthesis and biological evaluation of 2,3-dihydropyrano[2,3-f]chromen-4(8H)-one based hybrids as potential mitochondrial apoptosis inducers.

    Science.gov (United States)

    Sakthivel, Palaniappan; Ilangovan, Andivelu; Kaushik, Mahabir Prasad

    2016-10-21

    Synthesis of novel pyranochromanone amide hybrids, by combining pyranochromanone pharmacophore and privileged scaffolds such as 2-amino-1,3,4-thiadiaole/2-aminothiazole/aminopyridine/aminonaphthalene and anti-cancer evaluation of a series led us to discover a series of new chemical entities (NCEs) showing broad spectrum of anti-cancer activity against three different human cancer cell lines (MCF-7, A549 and HeLa), at IC50 values ranging from 14.3 to 97.8 μM. Among them, some compounds such as 15b, 15d, 20a and 20b displayed excellent activity against breast cancer cell line MCF-7. Detailed biological studies such as AO/EB dual staining, Hoechst 33342 staining, FACS analysis of mitochondrial membrane potential (Δψm) using JC-1 dye and DNA fragmentation confirmed the apoptosis induced by the hybrids. Gene expression studies by Real time RT-PCR has shown that these compounds are efficient regulator of anti-apoptotic gene Bcl-2. Western blot analysis also revealed that these compounds persuade apoptosis through intrinsic pathway by up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Molecular docking studies reveal that compounds 15b and 20b binds efficiently with Bcl-2 promoter G-quadruplex.

  2. Screening strategies for discovery of antibacterial natural products.

    Science.gov (United States)

    Singh, Sheo B; Young, Katherine; Miesel, Lynn

    2011-08-01

    Microbial-derived natural products have been a traditional source of antibiotics and antibiotic leads and continue to be effective sources of antibiotics today. The most important of these discoveries were made about 50 years ago. Chemical modifications of natural products discovered during those years continue to produce new clinical agents but their value is now, unfortunately, fading away owing to the exhaustion of opportunities of chemical modifications. The discovery of new natural antibiotics is directly linked to new screening technologies, particularly technologies that can help to eliminate the rediscovery of known antibiotics. In this article, we have reviewed the screening technologies from recent literature as well as originating from authors laboratories that were used for the screening of natural products. The article covers the entire spectrum of screening strategies, including classical empiric whole-cell assays to more sophisticated antisense based hypersensitive Staphylococcus aureus Fitness Test assays designed to screen all targets simultaneously. These technologies have led to the discovery of a series of natural product antibiotics, which have been summarized, including the discovery of platensimycin, platencin, nocathiacins, philipimycin, cyclothialidine and muryamycins. It is quite clear that natural products provide a tremendous opportunity to discover new antibiotics when combined with new hyper-sensitive whole-cell technologies.

  3. Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs.

    Science.gov (United States)

    Islam, Md Asiful; Alam, Fahmida; Khalil, Md Ibrahim; Sasongko, Teguh Haryo; Gan, Siew Hua

    2016-01-01

    Globally, thrombosis-associated disorders are one of the main contributors to fatalities. Besides genetic influences, there are some acquired and environmental risk factors dominating thrombotic diseases. Although standard regimens have been used for a long time, many side effects still occur which can be life threatening. Therefore, natural products are good alternatives. Although the quest for antithrombotic natural products came to light only since the end of last century, in the last two decades, a considerable number of natural products showing antithrombotic activities (antiplatelet, anticoagulant and fibrinolytic) with no or minimal side effects have been reported. In this review, several natural products used as antithrombotic agents including medicinal plants, vegetables, fruits, spices and edible mushrooms which have been discovered in the last 15 years and their target sites (thrombogenic components, factors and thrombotic pathways) are described. In addition, the side effects, limitations and interactions of standard regimens with natural products are also discussed. The active compounds could serve as potential sources for future research on antithrombotic drug development. As a future direction, more advanced researches (in quest of the target cofactor or component involved in antithrombotic pathways) are warranted for the development of potential natural antithrombotic medications (alone or combined with standard regimens) to ensure maximum safety and efficacy.

  4. Plant-Derived Natural Products for Parkinson's Disease Therapy.

    Science.gov (United States)

    Sengupta, T; Vinayagam, J; Singh, R; Jaisankar, P; Mohanakumar, K P

    2016-01-01

    Plant-derived natural products have made their own niche in the treatment of neurological diseases since time immemorial. Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, has no cure and the treatment available currently is symptomatic. This chapter thoughtfully and objectively assesses the scientific basis that supports the increasing use of these plant-derived natural products for the treatment of this chronic and progressive disorder. Proper considerations are made on the chemical nature, sources, preclinical tests and their validity, and mechanisms of behavioural or biochemical recovery observed following treatment with various plants derived natural products relevant to PD therapy. The scientific basis underlying the neuroprotective effect of 6 Ayurvedic herbs/formulations, 12 Chinese medicinal herbs/formulations, 33 other plants, and 5 plant-derived molecules have been judiciously examined emphasizing behavioral, cellular, or biochemical aspects of neuroprotection observed in the cellular or animal models of the disease. The molecular mechanisms triggered by these natural products to promote cell survivability and to reduce the risk of cellular degeneration have also been brought to light in this study. The study helped to reveal certain limitations in the scenario: lack of preclinical studies in all cases barring two; heavy dependence on in vitro test systems; singular animal or cellular model to establish any therapeutic potential of drugs. This strongly warrants further studies so as to reproduce and confirm these reported effects. However, the current literature offers scientific credence to traditionally used plant-derived natural products for the treatment of PD.

  5. A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives: Formal synthesis of naturally occurring norephedrine, virolin and 3-hydroxy-2-phosphonylmethoxypropyl adenine

    Indian Academy of Sciences (India)

    S Saha; P Chakraborty; S C Roy

    2014-05-01

    A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin and 3-hydroxy-2-phosphonylmethoxypropyl adenine has been demonstrated.

  6. Chitin elicitation of natural product production in marine bacteria

    DEFF Research Database (Denmark)

    Månsson, Maria; Wietz, Matthias; Larsen, Thomas Ostenfeld

    Genome sequences reveal that our current standard laboratory conditions only support a fraction of the potential secondary metabolism in bacteria.1 Thus, we must rethink cultivation, detection, and isolation strategies for bacterial secondary metabolites in order to explore the huge, so far...... uncharacterized chemical potential of these organisms. As part of a new project on ecology-driven drug discovery at the Technical University of Denmark, we investigate the use of chitin to elicit or alter production of antibacterial compounds in marine bacteria. Within our large collection of Gram......-negative bacteria (mainly Pseudoalteromonas and Vibrio), we found that some strains were capable of producing antibacterial compounds when grown on chitin, an N-acetyl-D-glucosamine polymer found in the exoskeleton of zooplankton.2 A strain of Vibrio coralliilyticus solely produced the antibiotic andrimid,3...

  7. Synthesis gas production from various biomass feedstocks

    Directory of Open Access Journals (Sweden)

    Juan A. Conesa

    2013-10-01

    Full Text Available The decomposition of five different biomass samples was studied in a horizontal laboratory reactor. The samples consisted of esparto grass, straw, Posidonea Oceanic seaweed, waste from urban and agricultural pruning and waste from forest pruning. Both pyrolysis in inert atmosphere and combustion in the presence of oxygen were studied. Different heating rates were used by varying the input speed. Major gas compounds were analyzed. The experimental results show that the amount of CO formed is lower in less dense species. It is also found that there is an increase of hydrocarbons formed at increasing feeding rates, in particular methane, while there is a decrease in the production of hydrogen.

  8. Template free synthesis of natural carbohydrates functionalised fluorescent silver nanoclusters.

    Science.gov (United States)

    Ebrahiminezhad, Alireza; Berenjian, Aydin; Ghasemi, Younes

    2016-06-01

    Template-assisted synthesis is one of the most recognised techniques for fabrication of silver nanoclusters (AgNCs). However, this process is time consuming, toxic and expensive. In this study, the authors report a completely novel approach for the green and facile synthesis of AgNCs using Matricaria chamomilla, without any additional template. Fluorescent and colloidally stable AgNCs with average particle size of 2.4 nm were successfully produced. They found that carbohydrates from Matricaria chamomilla act as an ideal template to generate fluorescent AgNCs. Moreover, oxygen-bearing functional groups were validated to be the active groups for anchoring and reducing of Ag(+) ions. The novel carbohydrate coating method makes the prepared nanoclusters completely hydrophilic and stable in aqueous matrices.

  9. New Synthesis of TATB. Scaleup and Product Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, R.D.; Mitchell, A.R.; Lee, G.S.; Pagoria, P.F.; Coburn, M.D.; Quinlan, W.T.; Thorpe, R.; Cates, M.

    2000-03-15

    At the 29th International Annual Conference of ICT (1998), the authors described the results of laboratory-scale process development studies for a new synthesis of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). This new synthesis approach--which uses vicarious nucleophilic substitution (VNS) methodology--converts picramide to TATB in high yield, and potentially at lower cost and with few environmental effects than existing synthetic approaches. In this report they describe results of their work on producing TATB by the VNS method at the pilot plant scale. They will discuss structure and control of impurities, changes in yield/quality with reaction conditions, choice of solvents, workup and product isolation, safety, and environmental considerations. Product characterization (particle size, DSC, HPLC, etc.) as well as small-scale safety and performance testing is also discussed.

  10. Hypervalent Iodine-Induced Oxidative Couplings (New Metal-Free Coupling Advances and Their Applications in Natural Product Syntheses).

    Science.gov (United States)

    Dohi, Toshifumi; Kita, Yasuyuki

    2016-01-01

    Recently, hypervalent iodine reagents have been extensively used in organic synthesis. A variety of reactions available for natural product syntheses have been developed using phenyliodine(III) diacetate (PIDA), phenyliodine(III) bis(trifluoroacetate) (PIFA), and other iodine(III) and (V) reagents. These reactions are expected to have applications in pharmaceutical and agrochemical processes because of their safety, mild reaction conditions, and high yields of pure products. Under such considerations, this chapter focuses on the oxidative coupling reactions of hypervalent iodine reagents found in total syntheses of biologically active natural products and their related compounds.

  11. Literature Review and Synthesis for the Natural Gas Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Folga, Stephen [Argonne National Lab. (ANL), Argonne, IL (United States); Talaber, Leah [Argonne National Lab. (ANL), Argonne, IL (United States); McLamore, Michael [Argonne National Lab. (ANL), Argonne, IL (United States); Kraucunas, Ian [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McPherson, Timothy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Parrott, Lori [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Manzanares, Trevor [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-06-01

    The efficient and effective movement of natural gas from producing regions to consuming regions requires an extensive and elaborate transportation system. In many instances, natural gas produced from a particular well has to travel a great distance to reach its point of use. The transportation system for natural gas consists of a complex network of pipelines designed to quickly and efficiently transport the gas from its origin to areas of high demand. The transportation of natural gas is closely linked to its storage: If the natural gas being transported is not immediately required, it can be put into storage facilities until it is needed. A description of the natural gas transmission, storage, and distribution (TS&D) sector is provided as follows.

  12. Evaluation of Reformer Produced Synthesis Gas for Emissions Reductions in Natural Gas Reciprocating Engines

    Energy Technology Data Exchange (ETDEWEB)

    Mark Scotto

    2010-05-30

    Rolls-Royce Fuel Cell Systems (US) Inc. (RRFCS) has developed a system that produces synthesis gas from air and natural gas. A near-term application being considered for this technology is synthesis gas injection into reciprocating engines for reducing NO{sub x} emissions. A proof of concept study using bottled synthesis gas and a two-stroke reciprocating engine showed that injecting small amounts of high-flammable content synthesis gas significantly improved combustion stability and enabled leaner engine operation resulting in over 44% reduction in NO{sub x} emissions. The actual NO{sub x} reduction that could be achieved in the field is expected to be engine specific, and in many cases may be even greater. RRFCS demonstrated that its synthesis gas generator could produce synthesis gas with the flammable content that was successfully used in the engine testing. An economic analysis of the synthesis gas approach estimates that its initial capital cost and yearly operating cost are less than half that of a competing NO{sub x} reduction technology, Selective Catalytic Reduction. The next step in developing the technology is an integrated test of the synthesis gas generator with an engine to obtain reliability data for system components and to confirm operating cost. RRFCS is actively pursuing opportunities to perform the integrated test. A successful integrated test would demonstrate the technology as a low-cost option to reduce NO{sub x} emissions from approximately 6,000 existing two-stroke, natural gas-fired reciprocating engines used on natural gas pipelines in North America. NO{sub x} emissions reduction made possible at a reasonable price by this synthesis gas technology, if implemented on 25% of these engines, would be on the order of 25,000 tons/year.

  13. Evaluation of Reformer Produced Synthesis Gas for Emissions Reductions in Natural Gas Reciprocating Engines

    Energy Technology Data Exchange (ETDEWEB)

    Mark V. Scotto; Mark A. Perna

    2010-05-30

    Rolls-Royce Fuel Cell Systems (US) Inc. (RRFCS) has developed a system that produces synthesis gas from air and natural gas. A near-term application being considered for this technology is synthesis gas injection into reciprocating engines for reducing NOx emissions. A proof of concept study using bottled synthesis gas and a two-stroke reciprocating engine showed that injecting small amounts of highflammables content synthesis gas significantly improved combustion stability and enabled leaner engine operation resulting in over 44% reduction in NOx emissions. The actual NOx reduction that could be achieved in the field is expected to be engine specific, and in many cases may be even greater. RRFCS demonstrated that its synthesis gas generator could produce synthesis gas with the flammables content that was successfully used in the engine testing. An economic analysis of the synthesis gas approach estimates that its initial capital cost and yearly operating cost are less than half that of a competing NOx reduction technology, Selective Catalytic Reduction. The next step in developing the technology is an integrated test of the synthesis gas generator with an engine to obtain reliability data for system components and to confirm operating cost. RRFCS is actively pursuing opportunities to perform the integrated test. A successful integrated test would demonstrate the technology as a low-cost option to reduce NOx emissions from approximately 6,000 existing two-stroke, natural gas-fired reciprocating engines used on natural gas pipelines in North America. NOx emissions reduction made possible at a reasonable price by this synthesis gas technology, if implemented on 25% of these engines, would be on the order of 25,000 tons/year.

  14. Computer-Aided Drug Design of Bioactive Natural Products.

    Science.gov (United States)

    Prachayasittikul, Veda; Worachartcheewan, Apilak; Shoombuatong, Watshara; Songtawee, Napat; Simeon, Saw; Prachayasittikul, Virapong; Nantasenamat, Chanin

    2015-01-01

    Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being.

  15. The Traditional Medicine and Modern Medicine from Natural Products

    Directory of Open Access Journals (Sweden)

    Haidan Yuan

    2016-04-01

    Full Text Available Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

  16. The Traditional Medicine and Modern Medicine from Natural Products.

    Science.gov (United States)

    Yuan, Haidan; Ma, Qianqian; Ye, Li; Piao, Guangchun

    2016-04-29

    Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

  17. Capillary electrophoresis of natural products: 2011-2012.

    Science.gov (United States)

    Tubaon, Ria Marni S; Rabanes, Heide; Haddad, Paul R; Quirino, Joselito P

    2014-01-01

    Bioactive natural products are major sources of lead compounds for drug discovery and pharmaceutical development, therefore, innovative and current separation and characterization techniques are important for these compounds. Here, CE methods applied for the analysis of natural products published during 2011-2012 are reviewed. This is an updated version of an earlier review paper in this journal, which highlighted developments during 2006-2010. The major method developments over the review period centered on derivatization, chiral analysis, modes of detection, stacking or on-line sample concentration, and sample preparation (predominantly using extraction methods). The samples analyzed were herbal products, foods, soil, and biological samples. Developments also occurred in the areas of quality control, toxicology assessment, and enzyme-inhibitor screening. A table that summarizes the areas, source of natural product, nature of the bioactive analyte, CE conditions, LODs, and corresponding reference is provided. A short description on the theory of CE and insights on future activities of CE on natural products are also presented.

  18. Culture-independent discovery of natural products from soil metagenomes.

    Science.gov (United States)

    Katz, Micah; Hover, Bradley M; Brady, Sean F

    2016-03-01

    Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.

  19. An Innovative Methodology of Product Design from Nature

    Institute of Scientific and Technical Information of China (English)

    Hui-I Wen; Shu-jun Zhang; Kevin Hapeshi; Xiao-feng Wang

    2008-01-01

    Nature is an information sourcebeok of behaviour, function, colour and shape which can inspire visual design and invention. Studying the form and functional characteristics of a natural object can provide inspiration for product design and help to improve the marketability of manufactured products. The inspiration can be triggered either by direct observation or captured by threo-dimensional (3D) digitising techniques to obtain superficial information (geometry and colour). An art designer often creates a concept in the form of a two-dimensional (2D) sketch while engineering methods lead to a point cloud in 3D. Each has its limitations in that the art designer commonly lacks the knowledge to build a final product from a 2D sketch and the engineering designer's 3D point clouds may not be very beautiful. We propose a method for Product Design from Nature (PDN),coupling aesthetic intent and geometrical characteristics, exploring the interactions between designers and nature's systems in PDN. We believe that this approach would considerably reduce the lead time and cost of product design from nature.

  20. Potential antimalarials from African natural products: A reviw.

    Science.gov (United States)

    Lawal, Bashir; Shittu, Oluwatosin Kudirat; Kabiru, Adamu Yusuf; Jigam, Ali Audu; Umar, Maimuna Bello; Berinyuy, Eustace Bonghan; Alozieuwa, Blessing Uchenna

    2015-01-01

    Malaria remains an overwhelming infectious disease with significant health challenges in African and other endemic countries globally. Resistance to antimalarial drugs has become one of the most momentous challenges to human health, and thus has necessitated the hunt for new and effective drugs. Consequently, few decades have witnessed a surfeit of research geared to validate the effectiveness of commonly used traditionally medicines against malaria fever. The present review work focuses on documenting natural products from African whose activity has been reported in vivo or in vitro against malaria parasite. Literature was collected using electronic search of published articles (Google Scholar, PubMed, Medline, Sciencedirect, and Science domain) that report on antiplasmodial activity of natural products from differernts Africa region. A total of 652 plant taxa from 146 families, 134 isolated antimalarial compounds from 39 plants species, 2 herbal formulations and 4 insect/products were found to be reported in literature from 1996 to 2015. Plants species from family Asteraceae (11.04%), Fababceae (8.128%), Euphorbiaceae (5.52%), Rubiaceas (5.52%), and Apocyanaceae (5.214%), have received more scientific validation than others. African natural products possess remarkable healing properties as revealed in the various citations as promising antimalarial agents. Some of these natural products from Africa demonstrate high, promising or low activities against Plasmodium parasite. This study also shows that natural products from Africa have a huge amount of novel antimalarial compounds that could serve as a leads for the development of new and effective antiplasmodial drugs. However, in a view of bridging the gap in knowledge, clinical validation of these natural products are of paramount importance.

  1. Discovery and resupply of pharmacologically active plant-derived natural products: A review.

    Science.gov (United States)

    Atanasov, Atanas G; Waltenberger, Birgit; Pferschy-Wenzig, Eva-Maria; Linder, Thomas; Wawrosch, Christoph; Uhrin, Pavel; Temml, Veronika; Wang, Limei; Schwaiger, Stefan; Heiss, Elke H; Rollinger, Judith M; Schuster, Daniela; Breuss, Johannes M; Bochkov, Valery; Mihovilovic, Marko D; Kopp, Brigitte; Bauer, Rudolf; Dirsch, Verena M; Stuppner, Hermann

    2015-12-01

    Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

  2. Synthesis of Nature-Inspired Medium-Sized Fused Heterocycles from Amino Acids.

    Science.gov (United States)

    Ventosa-Andrés, Pilar; La-Venia, Agustina; Ripoll, Carlos Alfonso Barea; Hradilová, Ludmila; Krchňák, Viktor

    2015-09-07

    Herein, we describe the synthesis of molecular scaffolds consisting of medium-sized fused heterocycles using amino acids, which are some of the most useful building blocks used by nature as well as chemists to create structural diversity. The acyclic precursors were assembled by using traditional Merrifield solid-phase peptide synthesis, and cyclization was carried out through acid-mediated tandem endocyclic N-acyliminium ion formation, followed by nucleophilic addition with internal nucleophiles. The synthesis of molecular scaffolds consisting of seven-, eight-, and nine-membered rings proceeded with full stereocontrol of the newly generated stereogenic center in most cases.

  3. Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.

    Science.gov (United States)

    Ju, Kou-San; Gao, Jiangtao; Doroghazi, James R; Wang, Kwo-Kwang A; Thibodeaux, Christopher J; Li, Steven; Metzger, Emily; Fudala, John; Su, Joleen; Zhang, Jun Kai; Lee, Jaeheon; Cioni, Joel P; Evans, Bradley S; Hirota, Ryuichi; Labeda, David P; van der Donk, Wilfred A; Metcalf, William W

    2015-09-29

    Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed "genome mining" as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibacterial phosphonopeptide composed of aminomethylphosphonate in peptide linkage to a rare amino acid N(5)-hydroxyarginine; valinophos, an N-acetyl l-Val ester of 2,3-dihydroxypropylphosphonate; and phosphonocystoximate, an unusual thiohydroximate-containing molecule representing a new chemotype of sulfur-containing phosphonate natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products.

  4. Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer

    Science.gov (United States)

    Macha, Muzafar A.; Krishn, Shiv Ram; Jahan, Rahat; Banerjee, Kasturi; Batra, Surinder K.; Jain, Maneesh

    2015-01-01

    Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders and has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy. PMID:25624117

  5. Establishment of new crops for the production of natural rubber.

    Science.gov (United States)

    van Beilen, Jan B; Poirier, Yves

    2007-11-01

    Natural rubber is a unique biopolymer of strategic importance that, in many of its most significant applications, cannot be replaced by synthetic alternatives. The rubber tree Hevea brasiliensis is the almost exclusive commercial source of natural rubber currently and alternative crops should be developed for several reasons, including: a disease risk to the rubber tree that could potentially decimate current production, a predicted shortage of natural rubber supply, increasing allergic reactions to rubber obtained from the Brazilian rubber tree and a general shift towards renewables. This review summarizes our knowledge of plants that can serve as alternative sources of natural rubber, of rubber biosynthesis and the scientific gaps that must be filled to bring the alternative crops into production.

  6. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.

    Science.gov (United States)

    Baud, Matthias G J; Leiser, Thomas; Meyer-Almes, Franz-Josef; Fuchter, Matthew J

    2011-02-07

    New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.

  7. Alkynol natural products target ALDH2 in cancer cells by irreversible binding to the active site.

    Science.gov (United States)

    Heydenreuter, Wolfgang; Kunold, Elena; Sieber, Stephan A

    2015-11-11

    Falcarinol and stipudiol are natural products with potent anti-cancer activity found in several vegetables. Here, we use a chemical proteomic strategy to identify ALDH2 as a molecular target of falcarinol in cancer cells and confirm enzyme inhibition via covalent alkylation of the active site. Furthermore, the synthesis of stipudiol led to the observation that ALDH2 exhibits preference for alkynol-based binders. Inhibition of ALDH2 impairs detoxification of reactive aldehydes and limits oxidative stress response, two crucial pathways for cellular viability.

  8. Natural product modulators to overcome multidrug resistance in cancer.

    Science.gov (United States)

    Cort, Aysegul; Ozben, Tomris

    2015-01-01

    Multidrug resistance (MDR) is a condition that makes cells simultaneously unresponsive to different drugs, unrelated to their chemical structure and mechanism of action. MDR caused by the presence and overexpression of ABC transporters makes obstacles in cancer treatment and lower the effectiveness of chemotherapy. Natural products are investigated by many researchers as MDR modulators for their low toxicity and potent, selective behavior. When coadministered, MDR modulators compete with cytotoxic agents for binding to the active site of the membrane transporters and reduce drug efflux. Natural product-based drugs are important in struggling against drug resistance during cancer therapy. This review is focused on the potential mechanisms against drug resistance, the development of inhibitors for ABC drug transporters, natural product modulators, and nanoparticle drug delivery.

  9. Dietary Natural Products for Prevention and Treatment of Liver Cancer

    Science.gov (United States)

    Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Li, Sha; Li, Hua-Bin

    2016-01-01

    Liver cancer is the most common malignancy of the digestive system with high death rate. Accumulating evidences suggests that many dietary natural products are potential sources for prevention and treatment of liver cancer, such as grapes, black currant, plum, pomegranate, cruciferous vegetables, French beans, tomatoes, asparagus, garlic, turmeric, ginger, soy, rice bran, and some edible macro-fungi. These dietary natural products and their active components could affect the development and progression of liver cancer in various ways, such as inhibiting tumor cell growth and metastasis, protecting against liver carcinogens, immunomodulating and enhancing effects of chemotherapeutic drugs. This review summarizes the potential prevention and treatment activities of dietary natural products and their major bioactive constituents on liver cancer, and discusses possible mechanisms of action. PMID:26978396

  10. Plant extracts as natural antioxidants in meat and meat products.

    Science.gov (United States)

    Shah, Manzoor Ahmad; Bosco, Sowriappan John Don; Mir, Shabir Ahmad

    2014-09-01

    Antioxidants are used to minimize the oxidative changes in meat and meat products. Oxidative changes may have negative effects on the quality of meat and meat products, causing changes in their sensory and nutritional properties. Although synthetic antioxidants have already been used but in recent years, the demand for natural antioxidants has been increased mainly because of adverse effects of synthetic antioxidants. Thus most of the recent investigations have been directed towards the identification of natural antioxidants from various plant sources. Plant extracts have been prepared using different solvents and extraction methods. Grape seed, green tea, pine bark, rosemary, pomegranate, nettle and cinnamon have exhibited similar or better antioxidant properties compared to some synthetic ones. This review provides the recent information on plant extracts used as natural antioxidants in meat and meat products, specifically red meat. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Bioactive natural products from Chinese marine flora and fauna

    Institute of Scientific and Technical Information of China (English)

    Zhen-fang ZHOU; Yue-wei GUO

    2012-01-01

    In recent decades,the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists.Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges,soft corals,and mollusks),resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins.Of particular interest is the fact that many of these compounds show promising biological activities,including cytotoxic,antibacterial,and enzyme inhibitory effects- By describing representative studies,this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade.Several interesting examples are discussed in detail.

  12. Dietary Natural Products for Prevention and Treatment of Liver Cancer

    Directory of Open Access Journals (Sweden)

    Yue Zhou

    2016-03-01

    Full Text Available Liver cancer is the most common malignancy of the digestive system with high death rate. Accumulating evidences suggests that many dietary natural products are potential sources for prevention and treatment of liver cancer, such as grapes, black currant, plum, pomegranate, cruciferous vegetables, French beans, tomatoes, asparagus, garlic, turmeric, ginger, soy, rice bran, and some edible macro-fungi. These dietary natural products and their active components could affect the development and progression of liver cancer in various ways, such as inhibiting tumor cell growth and metastasis, protecting against liver carcinogens, immunomodulating and enhancing effects of chemotherapeutic drugs. This review summarizes the potential prevention and treatment activities of dietary natural products and their major bioactive constituents on liver cancer, and discusses possible mechanisms of action.

  13. In situ natural product discovery via an artificial marine sponge.

    Directory of Open Access Journals (Sweden)

    James J La Clair

    Full Text Available There is continuing international interest in exploring and developing the therapeutic potential of marine-derived small molecules. Balancing the strategies for ocean based sampling of source organisms versus the potential to endanger fragile ecosystems poses a substantial challenge. In order to mitigate such environmental impacts, we have developed a deployable artificial sponge. This report provides details on its design followed by evidence that it faithfully recapitulates traditional natural product collection protocols. Retrieving this artificial sponge from a tropical ecosystem after deployment for 320 hours afforded three actin-targeting jasplakinolide depsipeptides that had been discovered two decades earlier using traditional sponge specimen collection and isolation procedures. The successful outcome achieved here could reinvigorate marine natural products research, by producing new environmentally innocuous sources of natural products and providing a means to probe the true biosynthetic origins of complex marine-derived scaffolds.

  14. Anti-cancer natural products isolated from chinese medicinal herbs

    Directory of Open Access Journals (Sweden)

    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  15. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  16. Knowledge based decision making: perspective on natural gas production

    Energy Technology Data Exchange (ETDEWEB)

    Ydstie, B. Erik; Stuland, Kjetil M.

    2009-07-01

    Conclusions (drawn by the author): Decarbonization of energy sources - From coal to renewable. Natural Gas Abundantly available - Norway is no. 3 exporter. Natural gas important as - Hydrogen source for chemicals; - Electricity; - End consumer usage (heating etc). Large potential for application of model based decision making; - Where and when to install platforms and drill wells - How to operate platforms and pipeline systems; - How to operate and optimize chemical production; - Optimization of electricity generation systems. (author)

  17. Synthesis of zeolite phases from combustion by-products

    Energy Technology Data Exchange (ETDEWEB)

    Pimraksa, K.; Chindaprasirt, P.; Setthaya, N. [Chiang Mai University, Chiang Mai (Thailand). Dept. of Industrial Chemistry

    2010-12-15

    Synthesis of zeolites from combustion by-products, including fly ash, bottom ash and rice husk ash, was studied. A molar ratio of SiO{sub 2}/Al2O{sub 3} of 1.5 was used for the syntheses. Refluxing and hydrothermal methods were also used for synthesis for comparison. The reaction temperatures of refluxing and hydrothermal methods were 100{sup o}C and 130{sup o}C, respectively. Sodalite, phillipsite-K, and zeolite P1 with analcime were obtained when fly ash, bottom ash and rice husk ash were used as starting materials, respectively. With rice husk ash as a starting material, zeolite P1 was produced. This result had advantages over previous studies as there was no prior activation required for the synthesis. The concentrations and types of alkaline used in the synthesis also determined the zeolite type. The different zeolites obtained from three systems were measured for specific surface area and pore size by using BET and Hg-porosimetry, respectively. Ammonium exchange capacities of the synthesised powders containing zeolites, sodalite, zeolite P1 and phillipsite-K were 38.5, 65.0 and 154.7 meq 100 g{sup 1}, respectively.

  18. Synthesis of zeolite phases from combustion by-products.

    Science.gov (United States)

    Pimraksa, Kedsarin; Chindaprasirt, Prinya; Setthaya, Naruemon

    2010-12-01

    Synthesis of zeolites from combustion by-products, including fly ash, bottom ash and rice husk ash, was studied. A molar ratio of SiO2/Al2O3 of 1.5 was used for the syntheses. Refluxing and hydrothermal methods were also used for synthesis for comparison. The reaction temperatures of refluxing and hydrothermal methods were 100 degrees C and 130 degrees C, respectively. Sodalite, phillipsite-K, and zeolite P1 with analcime were obtained when fly ash, bottom ash and rice husk ash were used as starting materials, respectively. With rice husk ash as a starting material, zeolite P1 was produced. This result had advantages over previous studies as there was no prior activation required for the synthesis. The concentrations and types of alkaline used in the synthesis also determined the zeolite type. The different zeolites obtained from three systems were measured for specific surface area and pore size by using BET and Hg-porosimetry, respectively. Ammonium exchange capacities of the synthesised powders containing zeolites, sodalite, zeolite P1 and phillipsite-K were 38.5, 65.0 and 154.7 meq 100 g(-1), respectively.

  19. Metal and metalloid containing natural products and a brief overview of their applications in biology, biotechnology and biomedicine.

    Science.gov (United States)

    Dias, Daniel A; Kouremenos, Konstantinos A; Beale, David J; Callahan, Damien L; Jones, Oliver A H

    2016-02-01

    Bioinorganic natural product chemistry is a relatively unexplored but rapidly developing field with enormous potential for applications in biology, biotechnology (especially in regards to nanomaterial development, synthesis and environmental cleanup) and biomedicine. In this review the occurrence of metals and metalloids in natural products and their synthetic derivatives are reviewed. A broad overview of the area is provided followed by a discussion on the more common metals and metalloids found in natural sources, and an overview of the requirements for future research. Special attention is given to metal hyperaccumulating plants and their use in chemical synthesis and bioremediation, as well as the potential uses of metals and metalloids as therapeutic agents. The potential future applications and development in the field are also discussed.

  20. The impact of natural products upon modern drug discovery.

    Science.gov (United States)

    Ganesan, A

    2008-06-01

    In the period 1970-2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the 'Lipinski universe' and complies with the Rule of Five. The second is a 'parallel universe' that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of logP and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug.

  1. SCHEMES OF GAS PRODUCTION FROM NATURAL GAS HYDRATES

    Institute of Scientific and Technical Information of China (English)

    李淑霞; 陈月明; 杜庆军

    2003-01-01

    Natural gas hydrates are a kind of nonpolluting and high quality energy resources for future, the reserves of which are about twice of the carbon of the current fossil energy (petroleum, natural gas and coal) on the earth. And it will be the most important energy for the 21st century. The energy balance and numerical simulation are applied to study the schemes of the natural gas hydrates production in this paper,and it is considered that both depressurization and thermal stimulation are effective methods for exploiting natural gas hydrates, and that the gas production of the thermal stimulation is higher than that of the depressurization. But thermal stimulation is non-economic because it requires large amounts of energy.Therefore the combination of the two methods is a preferable method for the current development of the natural gas hydrates. The main factors which influence the production of natural gas hydrates are: the temperature of injected water, the injection rate, the initial saturation of the hydrates and the initial temperature of the reservoir which is the most important factor.

  2. Patentability potential of natural products for xerostomia treatment

    OpenAIRE

    2016-01-01

    Xerostomia is characterized as a symptom caused by hyposalivation, which can occur for reasons such as age, polypharmacy, radiation therapy, among others. Currently,few products are available for the treatment of xerostomia, which is a subject still underestimated by many health professionals. Thus, we searched patents applied and approved in Brazil on xerostomia, to verify the existing innovation involving natural products. We found 33 patents applied and approved in Brazil, many of them usi...

  3. Catalytic Production of Ethanol from Biomass-Derived Synthesis Gas

    Energy Technology Data Exchange (ETDEWEB)

    Trewyn, Brian G. [Colorado School of Mines, Golden, CO (United States); Smith, Ryan G. [Iowa State Univ., Ames, IA (United States)

    2016-06-01

    Heterogeneous catalysts have been developed for the conversion of biomass-derived synthetic gas (syngas) to ethanol. The objectives of this project were to develop a clean synthesis gas from biomass and develop robust catalysts with high selectivity and lifetime for C2 oxygenate production from biomass-derived syngas and surrogate syngas. During the timeframe for this project, we have made research progress on the four tasks: (1) Produce clean bio-oil generated from biomass, such as corn stover or switchgrass, by using fast pyrolysis system, (2) Produce clean, high pressure synthetic gas (syngas: carbon monoxide, CO, and hydrogen, H2) from bio-oil generated from biomass by gasification, (3) Develop and characterize mesoporous mixed oxide-supported metal catalysts for the selective production of ethanol and other alcohols, such as butanol, from synthesis gas, and (4) Design and build a laboratory scale synthesis gas to ethanol reactor system evaluation of the process. In this final report, detailed explanations of the research challenges associated with this project are given. Progress of the syngas production from various biomass feedstocks and catalyst synthesis for upgrading the syngas to C2-oxygenates is included. Reaction properties of the catalyst systems under different reaction conditions and different reactor set-ups are also presented and discussed. Specifically, the development and application of mesoporous silica and mesoporous carbon supports with rhodium nanoparticle catalysts and rhodium nanoparticle with manganese catalysts are described along with the significant material characterizations we completed. In addition to the synthesis and characterization, we described the activity and selectivity of catalysts in our micro-tubular reactor (small scale) and fixed bed reactor (larger scale). After years of hard work, we are proud of the work done on this project, and do believe that this work will provide a solid

  4. Idaho Habitat and Natural Production Monitoring : Annual Report 1989.

    Energy Technology Data Exchange (ETDEWEB)

    Kiefer, Russell B.; Forster, Katharine A.

    1991-01-01

    Project 83-7 was established under the Northwest Power Planning Council's 1982 Fish and Wildlife Program to monitor natural production of anadromous fish, evaluate Bonneville Power Administration (BPA) habitat improvement projects, and develop a credit record for off-site mitigation projects in Idaho. Project 83-7 is divided into two subprojects: general and intensive monitoring. Primary objectives of the general monitoring subproject (Part 1) are to determine natural production increases due to habitat improvement projects in terms of parr production and to determine natural production status and trends in Idaho. The second objective is accomplished by combining parr density data from monitoring and evaluation of BPA habitat projects and from other Idaho Department of Fish and Game (IDFG) management and research activities. Primary objectives of the intensive monitoring subproject (Part 2) are to determine the number of returning chinook and steelhead adults necessary to achieve optimal smolt production and to develop mitigation accounting based on increases in smolt production. Two locations are being intensively studied to meet these objectives. Field work began in 1987 in the upper Salmon River and Crooked River (South Fork Clearwater River tributary). 22 refs., 10 figs., 17 tabs.

  5. Pseudomonas putida—a versatile host for the production of natural products

    OpenAIRE

    Loeschcke, Anita; Thies, Stephan

    2015-01-01

    The biosynthesis of natural products by heterologous expression of biosynthetic pathways in amenable production strains enables biotechnological access to a variety of valuable compounds by conversion of renewable resources. Pseudomonas putida has emerged as a microbial laboratory work horse, with elaborated techniques for cultivation and genetic manipulation available. Beyond that, this bacterium offers several particular advantages with regard to natural product biosynthesis, notably a vers...

  6. The EROI of Conventional Canadian Natural Gas Production

    Directory of Open Access Journals (Sweden)

    Jon Freise

    2011-11-01

    Full Text Available Canada was the world’s third largest natural gas producer in 2008, with 98% of its gas being produced by conventional, tight gas, and coal bed methane wells in Western Canada. Natural gas production in Western Canada peaked in 2001 and remained nearly flat until 2006 despite more than quadrupling the drilling rate. Canada seems to be one of many counter examples to the idea that oil and gas production can rise with sufficient investment. This study calculated the Energy Return on Energy Invested and Net Energy of conventional natural gas and oil production in Western Canada by a variety of methods to explore the energy dynamics of the peaking process. All these methods show a downward trend in EROI during the last decade. Natural gas EROI fell from 38:1 in 1993 to 15:1 at the peak of drilling in 2005. The drilling intensity for natural gas was so high that net energy delivered to society peaked in 2000–2002, while production did not peak until 2006. The industry consumed all the extra energy it delivered to maintain the high drilling effort. The inability of a region to increase net energy may be the best definition of peak production. This increase in energy consumption reduces the total energy provided to society and acts as a contracting pressure on the overall economy as the industry consumes greater quantities of labor, steel, concrete and fuel. It appears that energy production from conventional oil and gas in Western Canada has peaked and entered permanent decline.

  7. Natural products as storage media for avulsed tooth

    Directory of Open Access Journals (Sweden)

    Deepika Jain

    2015-01-01

    Full Text Available Avulsion of tooth is complete displacement of tooth out of its socket that results in mutilation of periodontal ligaments. The desirable treatment option is replantation of the tooth. However, unsuccessful replantation is a matter of great discontentment. Unsuccessful replantation is due to inappropriate management of the avulsed tooth. Protection of teeth from desiccation due to drying of the periodontal ligament tissue, by keeping it in storage media can improve the outcome of the treatment. This review paper focuses on the use of natural products as storage media for avulsed teeth. In vitro and in vivo research published during 1995-2014, allowing open access on National Center for Biotechnology Information (NCBI database and articles on EBSCO host (EBSCO-Elton B. Stephens Company were included. It was found that natural products such as milk, coconut water, propolis, green tea, red mulberry, Aloe vera, egg-white and pomegranate have shown ability to maintain viability of periodontal ligament cells of avulsed teeth. Few natural products such as coconut water and milk can be used in raw form, while other products such as green tea and red mulberry need processing. Ability to maintain periodontal cell viability for a longer time is warranted in cases of major accidents, where teeth can be replanted only after other major surgeries. Natural products have easy availability, greater efficacy and longer storage time as compared to Hank′s balanced salt solution which has been recommended by the International Association of Dental Traumatology as standard solution for storage of avulsed teeth. Natural products have shown good qualities in in vitro experiments; further in vivo studies are needed to evaluate their efficacy as storage media.

  8. A Short Synthesis of Natural Isocoumarin Glucoside Delphoside

    Institute of Scientific and Technical Information of China (English)

    SAEED,Aamer

    2005-01-01

    A simple synthesis of delphoside, 3-methyl-6-hydroxy-8-O-β-D-glucopyranosyloxy isocoumarin (1), isolated from Delphinium spp. is described. 3,5-Dimethoxyhomophthalic anhydride (2) on treatment with acetyl chloride in the presence of 1,1,3,3-tetramethylguanidine (TMG) and triethyl amine afforded the 6,8-dimethoxy-3-methylisocoumarin (3). Regioselective demethylation of the latter furnished 8-hydroxy-6-methoxy-3-methylisocoumarin (4). Glycosylation with O-(2,3,4,6-tetra-O-acetyl-D-glucopyranosyl)trichloroacetimidate in presence of catalytic amount of boron trifluoride etherate followed by deacetylation using 5% potassium carbonate afforded 3-methyl-6-methoxy-8-O-β-D-glucopyranosyloxyisocoumarin (6) that was finally demethylated to yield delphoside 1.

  9. Production of hydrogen by thermocatalytic cracking of natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Muradov, N.Z. [Univ. of Central Florida, Cape Canaveral, FL (United States)

    1995-09-01

    It is universally accepted that in the next few decades hydrogen production will continue to rely on fossil fuels (primarily, natural gas). On the other hand, the conventional methods of hydrogen production from natural gas (for example, steam reforming) are complex multi-step processes. These processes also result in the emission of large quantities of CO{sub 2} into the atmosphere that produce adverse ecological effects. One alternative is the one-step thermocatalytic cracking (TCC) (or decomposition) of natural gas into hydrogen and carbon. Preliminary analysis indicates that the cost of hydrogen produced by thermal decomposition of natural gas is somewhat lower than the conventional processes after by-product carbon credit is taken. In the short term, this process can be used for on-site production of hydrogen-methane mixtures in gas-filling stations and for CO{sub x}-free production of hydrogen for fuel cell driven prime movers. The experimental data on the thermocatalytic cracking of methane over various catalysts and supports in a wide range of temperatures (500-900{degrees}C) are presented in this paper. Two types of reactors were designed and built at FSEC: continuous flow and pulse fix bed catalytic reactors. The temperature dependence of the hydrogen production yield using oxide type catalysts was studied. Alumina-supported Ni- and Fe-catalysts demonstrated relatively high efficiency in the methane cracking reaction at moderate temperatures (600-800{degrees}C). Kinetic curves of hydrogen production over metal and metal oxide catalysts at different temperatures are presented in the paper. Fe-catalyst demonstrated good stability (for several hours), whereas alumina-supported Pt-catalyst rapidly lost its catalytic activity.

  10. The catalytic conversion of natural gas to useful products

    NARCIS (Netherlands)

    Ross, J.R.H.; Ross, J.R.H.; van Keulen, A.N.J.; van Keulen, A.N.J.; Hegarty, M.E.S.; Seshan, Kulathuiyer

    1996-01-01

    This paper gives a brief summary of some processes, direct and indirect, for the conversion of natural gas to useful products. It then proceeds to give an outline of some work from the authors' laboratories on subjects such as steam reforming, oxidative coupling and CO2 reforming of methane, paying

  11. Liquefied natural gas production at Hammerfest: A transforming marine community

    NARCIS (Netherlands)

    Bets, van L.K.J.; Tatenhove, van J.P.M.; Mol, A.P.J.

    2016-01-01

    Global energy demand and scarce petroleum resources require communities to adapt to a rapidly changing Arctic environment, but as well to a transforming socio-economic environment instigated by oil and gas development. This is illustrated by liquefied natural gas production by Statoil at Hammerfest,

  12. The 9th European Conference on Marine Natural Products

    Directory of Open Access Journals (Sweden)

    RuAngelie Edrada-Ebel

    2015-12-01

    Full Text Available The 9th European Conference on Marine Natural Products (ECMNP in Glasgow follows its predecessors in La Toja (2013, Tjärnö (2011, Porto (2009, Ischia (2007, Paris (2005, Elmau (2002, Santiago de Compostela (1999, and Athens (1997. [...

  13. Bioactive Natural Products From Chinese Tropical Marine Organisms

    Institute of Scientific and Technical Information of China (English)

    GUO,Yue-Wei

    2004-01-01

    @@ The oceans contain a vast biological diversity of species that have so far been utilized by mankind mainly as a source of protein. In the last few decades, however, natural products chemists have started to discover the wealth of bioactive secondary metabolites that are produced by marine invertebrates such as sponges, soft corals, molluscs and others.

  14. Current perspectives in drug discovery against tuberculosis from natural products.

    Science.gov (United States)

    Nguta, Joseph Mwanzia; Appiah-Opong, Regina; Nyarko, Alexander K; Yeboah-Manu, Dorothy; Addo, Phyllis G A

    2015-09-01

    Currently, one third of the world's population is latently infected with Mycobacterium tuberculosis (MTB), while 8.9-9.9 million new and relapse cases of tuberculosis (TB) are reported yearly. The renewed research interests in natural products in the hope of discovering new and novel antitubercular leads have been driven partly by the increased incidence of multidrug-resistant strains of MTB and the adverse effects associated with the first- and second-line antitubercular drugs. Natural products have been, and will continue to be a rich source of new drugs against many diseases. The depth and breadth of therapeutic agents that have their origins in the secondary metabolites produced by living organisms cannot be compared with any other source of therapeutic agents. Discovery of new chemical molecules against active and latent TB from natural products requires an interdisciplinary approach, which is a major challenge facing scientists in this field. In order to overcome this challenge, cutting edge techniques in mycobacteriology and innovative natural product chemistry tools need to be developed and used in tandem. The present review provides a cross-linkage to the most recent literature in both fields and their potential to impact the early phase of drug discovery against TB if seamlessly combined.

  15. Low Carbon Technology Options for the Natural Gas Electricity Production

    Science.gov (United States)

    The ultimate goal of this task is to perform environmental and economic analysis of natural gas based power production technologies (different routes) to investigate and evaluate strategies for reducing emissions from the power sector. It is a broad research area. Initially, the...

  16. Solvent-free extraction of food and natural products

    OpenAIRE

    Fabiano-Tixier, Anne-Sylvie; Vian, Maryline; Allaf, Tamara; Vorobiev, Eugene

    2015-01-01

    This review presents useful and green techniques of solvent-free extraction used in ancient times, such as extraction of olive oil and citrus essential oil, and innovative techniques, such as pulsed electric field, microwave, instantaneous controlled pressure drop, and extrusion. We discuss the devices, their applications, mechanisms, and parameters influencing sample preparation prior to analysis of natural products.

  17. Low Carbon Technology Options for the Natural Gas Electricity Production

    Science.gov (United States)

    The ultimate goal of this task is to perform environmental and economic analysis of natural gas based power production technologies (different routes) to investigate and evaluate strategies for reducing emissions from the power sector. It is a broad research area. Initially, the...

  18. A New Golden Age of Natural Products Drug Discovery

    Science.gov (United States)

    Shen, Ben

    2016-01-01

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell and Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. PMID:26638061

  19. Natural products chemistry research 2010's progress in China.

    Science.gov (United States)

    Ye, Yang; Li, Xi-Qiang; Tang, Chun-Ping; Yao, Sheng

    2012-01-01

    This article reviews the progresses made by Chinese scientists in the field of natural products chemistry in 2010. Selected compounds with unique structural features and/or promising bioactivities were described herein on the basis of structural types. Copyright © 2012 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  20. Natural Products as Source of Therapeutics against Parasitic Diseases.

    Science.gov (United States)

    Hertweck, Christian

    2015-12-01

    An end to suffering: Parasitic infections with protozoa and worms cause unimaginable misery, in particular in the tropics. Fortunately, natural products, such as the antimalarial artemisinin (1) and the anthelmintic avermectin (2) were discovered and developed into therapeutics. These major achievements now culminated in the 2015 Nobel Prize for Medicine.

  1. Short history of natural product research in the CSIR

    CSIR Research Space (South Africa)

    Walwyn, D

    2006-02-01

    Full Text Available Natural product research has been a major component of the CSIR's bioscience activities for its entire history, and particularly in the 1960s and 1970s. This type of work is also strongly aligned with one of the objectives of the CSIR, namely...

  2. Natural product derived insecticides: discovery and development of spinetoram.

    Science.gov (United States)

    Galm, Ute; Sparks, Thomas C

    2016-03-01

    This review highlights the importance of natural product research and industrial microbiology for product development in the agricultural industry, based on examples from Dow AgroSciences. It provides an overview of the discovery and development of spinetoram, a semisynthetic insecticide derived by a combination of a genetic block in a specific O-methylation of the rhamnose moiety of spinosad coupled with neural network-based QSAR and synthetic chemistry. It also emphasizes the key role that new technologies and multidisciplinary approaches play in the development of current spinetoram production strains.

  3. HEURISTIC OPTIMIZATION OF NATURAL PRODUCTION INVENTORY MODELS WITH THE PREFERENCE OF A DECISION MAKER

    OpenAIRE

    CHIH HSUN HSIEH

    2008-01-01

    In this paper, two natural production inventory models based on fuzzy total production inventory cost with the preference of a decision maker are introduced, and combined by natural number parameters in which values are linguistic values in natural language, crisp real number variables, and fuzzy number variables. These are the one natural production inventory model for crisp production quantity, and the other natural production inventory model for fuzzy production quantity. The natural arith...

  4. Systematics-guided bioprospecting for bioactive microbial natural products.

    Science.gov (United States)

    Liu, Xueting; Bolla, Krishna; Ashforth, Elizabeth Jane; Zhuo, Ying; Gao, Hong; Huang, Pei; Stanley, Sarah A; Hung, Deborah T; Zhang, Lixin

    2012-01-01

    Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well.

  5. Synthetic biology tools for bioprospecting of natural products in eukaryotes.

    Science.gov (United States)

    Unkles, Shiela E; Valiante, Vito; Mattern, Derek J; Brakhage, Axel A

    2014-04-24

    Filamentous fungi have the capacity to produce a battery of natural products of often unknown function, synthesized by complex metabolic pathways. Unfortunately, most of these pathways appear silent, many in intractable organisms, and their products consequently unidentified. One basic challenge is the difficulty of expressing a biosynthesis pathway for a complex natural product in a heterologous eukaryotic host. Here, we provide a proof-of concept solution to this challenge and describe how the entire penicillin biosynthesis pathway can be expressed in a heterologous host. The method takes advantage of a combination of improved yeast in vivo cloning technology, generation of polycistronic mRNA for the gene cluster under study, and an amenable and easily manipulated fungal host, i.e., Aspergillus nidulans. We achieve expression from a single promoter of the pathway genes to yield a large polycistronic mRNA by using viral 2A peptide sequences to direct successful cotranslational cleavage of pathway enzymes.

  6. Natural products - plenty more where that came from

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, M.

    1980-12-22

    In this article, natural products and their possible use as renewable resources are reviewed. The fermentation of corn for the production of alcohol for motor fuel is discussed and other crops for this purpose include sugar cane, cassava, sweet potato and Jerusalem artichoke. The hydrolysis of cellulose to sugars based on enzyme hydrolysis is currently being researched in the USA. Also in the USA, Melvin Calvin hopes to breed a rubber-bearing plant whose latex can be easily cracked to motor fuel. Guayule and jojoba rubber-bearing plants are also the focus of research at present. The importance of natural vegetation in the manufacturing of medicines and in the chemical and food industries is stressed. Finally products of the sea, particularly alginates and carragheenins are mentioned, but as yet, the full potential of the sea to yield renewable resources is unknown.

  7. Virtual Natural Product Library - full text searchable database

    Directory of Open Access Journals (Sweden)

    Subhash Chandra Bose. Kotte

    2012-05-01

    Full Text Available Small molecules occurring in nature have special significance to mankind. They have varied applications from healthcare, food, nutrition, agriculture, personal care and well-being. These natural small molecules are from very diverse sources from the rarest plants to deep sea creatures. Recently they have assumed a lot of significance as pharmaceutical companies is constantly pushing the horizons to make them druggable due to their inherent bioactivities. Though they are not easy to synthesize or isolate, yet their diverse molecular scaffold confers them significance especially given the fact of prevailing resistance to drug scaffolds presently being used in the clinics. Hence its of paramount importance to have a database of diverse natural small molecules through the present effort of creating a Virtual Natural Products Library (VNPL-version 0.15.

  8. Infrared Spectroscopy Study of Structural Nature of Geopolymeric Products

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yunsheng; SUN Wei; LI Zongjin

    2008-01-01

    The bonding status and chemical environment of SiO4 and AlO4 tetrahedras of three types of geopolymeric products were systematically investigated by infrared spectroscopy.The relationship between amorphous geopolymeric products and zeolite crystals with the same overall chemical compositions was also discussed.The infrared evidence shows that SiO4 tetrahedra is partially bonded by AlO4 during the hydration process ofgeopolymeric cement.The two types of tetrahedras jointly construct the three dimensional framework structures of the geopolymeric products.The mutual transformation between geopolymeric products and corresponding zeolite crystals will take place once the reaction condition is suitable,which reveals that the nature ofgeopolymeric products are probably the amorphous equivalent of the corresponding zeolite crystals.

  9. Synthesis of New Anti-Cancer Natural Products

    DEFF Research Database (Denmark)

    Yu, Wanwan

    2016-01-01

    Cancer is one of the leading causes of morbidity and mortality worldwide, and more than 90% of the cancer-related deaths are due to the causes of metastatic pathological change. Tumor hypoxia, resulting from the inadequate blood supply in tumor tissues due to high cellular proliferation, is linked......M, respectively. In addition to the general potent cytotoxicity, rakicidins have been revealed to be distinct and potent hypoxia-selective cytotoxins in a variety of hypoxia induced drug resistant human cancer cell lines with rakicidin A as the pioneer. The unique and potent hypoxia-selective cytotoxicity makes...

  10. Synthesis Gas Production from Natural Gas on Supported Pt Catalysts

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Auto-thermal reforming of methane, combining partial oxidation and reforming of methane with CO2 or steam, was carried out with Pt/Al2O3, Pt/ZrO2 and Pt/CeO2 catalysts, in a temperature range of 300-900 ℃. The auto-thermal reforming occurs in two simultaneous stages, namely, total combustion of methane and reforming of the unconverted methane with steam and CO2, with the O2 conversion of 100% starting from 450 ℃. For combination with CO2 reforming, the Pt/CeO2 catalyst showed the lowest initial activity at 800 ℃, and the highest stability over 40 h on-stream. This catalyst also presented the best performance for the reaction with steam at 800 ℃. The higher resistance to coke formation of the catalyst supported on ceria is due to the metal-support interactions and the higher mobility of oxygen in the oxide lattice.

  11. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  12. Exploiting the potential of marine natural products: structure elucidation and metagenomic approaches to biotechnological production

    OpenAIRE

    Della Sala, Gerardo

    2013-01-01

    Sponges represent the most prolific producers of novel marine bioactive secondary metabolites. In the last years, several drugs derived from marine natural products have appeared in the market, and others are in clinical trials. The aim of my research project was to exploit the unusual and often surprising chemistry of marine sponges, in the frame of the more general purpose of discovering and developing new drugs from natural products. The research work presented in this PhD Thesis was di...

  13. Design, synthesis and decoration of molecular scaffolds for exploitation in the production of alkaloid-like libraries.

    Science.gov (United States)

    Craven, Philip; Aimon, Anthony; Dow, Mark; Fleury-Bregeot, Nicolas; Guilleux, Rachel; Morgentin, Remy; Roche, Didier; Kalliokoski, Tuomo; Foster, Richard; Marsden, Stephen P; Nelson, Adam

    2015-06-01

    The design, synthesis and decoration of six small molecule libraries is described. Each library was inspired by structures embedded in the framework of specific alkaloid natural products. The development of optimised syntheses of the required molecular scaffolds is described, in which reactions including Pd-catalysed aminoarylation and diplolar cycloadditions have been exploited as key steps. The synthesis of selected exemplar screening compounds is also described. In five cases, libraries were subsequently nominated for production on the basis of the scope and limitations of the validation work, as well as predicted molecular properties. In total, the research has led to the successful synthesis of >2500 novel alkaloid-like compounds for addition to the screening collection (the Joint European Compound Library, JECL) of the European Lead Factory.

  14. Next Generation Sequencing of Actinobacteria for the Discovery of Novel Natural Products

    Directory of Open Access Journals (Sweden)

    Juan Pablo Gomez-Escribano

    2016-04-01

    Full Text Available Like many fields of the biosciences, actinomycete natural products research has been revolutionised by next-generation DNA sequencing (NGS. Hundreds of new genome sequences from actinobacteria are made public every year, many of them as a result of projects aimed at identifying new natural products and their biosynthetic pathways through genome mining. Advances in these technologies in the last five years have meant not only a reduction in the cost of whole genome sequencing, but also a substantial increase in the quality of the data, having moved from obtaining a draft genome sequence comprised of several hundred short contigs, sometimes of doubtful reliability, to the possibility of obtaining an almost complete and accurate chromosome sequence in a single contig, allowing a detailed study of gene clusters and the design of strategies for refactoring and full gene cluster synthesis. The impact that these technologies are having in the discovery and study of natural products from actinobacteria, including those from the marine environment, is only starting to be realised. In this review we provide a historical perspective of the field, analyse the strengths and limitations of the most relevant technologies, and share the insights acquired during our genome mining projects.

  15. Next Generation Sequencing of Actinobacteria for the Discovery of Novel Natural Products.

    Science.gov (United States)

    Gomez-Escribano, Juan Pablo; Alt, Silke; Bibb, Mervyn J

    2016-04-13

    Like many fields of the biosciences, actinomycete natural products research has been revolutionised by next-generation DNA sequencing (NGS). Hundreds of new genome sequences from actinobacteria are made public every year, many of them as a result of projects aimed at identifying new natural products and their biosynthetic pathways through genome mining. Advances in these technologies in the last five years have meant not only a reduction in the cost of whole genome sequencing, but also a substantial increase in the quality of the data, having moved from obtaining a draft genome sequence comprised of several hundred short contigs, sometimes of doubtful reliability, to the possibility of obtaining an almost complete and accurate chromosome sequence in a single contig, allowing a detailed study of gene clusters and the design of strategies for refactoring and full gene cluster synthesis. The impact that these technologies are having in the discovery and study of natural products from actinobacteria, including those from the marine environment, is only starting to be realised. In this review we provide a historical perspective of the field, analyse the strengths and limitations of the most relevant technologies, and share the insights acquired during our genome mining projects.

  16. Dietary Natural Products for Prevention and Treatment of Breast Cancer.

    Science.gov (United States)

    Li, Ya; Li, Sha; Meng, Xiao; Gan, Ren-You; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-07-08

    Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.

  17. Utilization of compressed natural gas for the production of carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Kim-Yang Lee; Wei-Ming Yeoh; Siang-Piao Chai; Abdul Rahman Mohamed

    2012-01-01

    The present work aims at utilizing compressed natural gas (CNG) as carbon source for the synthesis of carbon nanotubes (CNTs) over CoO-MoO/Al2O3 catalyst via catalytic chemical vapor deposition (CCVD) method.The as-produced carbonaceous product was characterized by thermal gravimetric analyzer (TGA),scanning electron microscopy (SEM),transmission electron microscopy (TEM) and Raman spectroscopy.The experimental finding shows that CNTs were successfully produced from CNG while carbon nanofibers (CNFs) were formed as the side products.In addition,the catalytic activity and lifetime were found sustained and prolonged,as compared with using high purity methane as carbon source.The present study suggests an alternative route which can effectively produce CNTs and CNFs using low cost CNG.

  18. Optimizing patient care with "natural" products: treatment of hyperpigmentation.

    Science.gov (United States)

    Woolery-Lloyd, Heather; Friedman, Adam

    2009-06-01

    Patients with skin of color suffer from different cutaneous issues when compared with skin of light complexion, and therefore management of the former must be representative of these variations. The most common pigmentary complaints in patients with skin of color are post-inflammatory hyperpigmentation, melasma and sun-induced hyperpigmentation. Often, patients with darker skin will turn to naturally occurring ingredients over synthetic analogues both to satisfy cultural preferences and to limit potential adverse effects that have been tied to synthetics. Science-based natural products can offer an attractive adjunct to conventional therapies that treat melasma, post-inflammatory hyperpigmentaion, and other dyschromias. Increasing data on the biological effects and the efficacy of natural therapies support the use of these complementary therapies in treating hyperpigmentation.

  19. Nature as a source of inspiration for cationic lipid synthesis.

    Science.gov (United States)

    Labas, Romain; Beilvert, Fanny; Barteau, Benoit; David, Stéphanie; Chèvre, Raphaël; Pitard, Bruno

    2010-02-01

    Synthetic gene delivery systems represent an attractive alternative to viral vectors for DNA transfection. Cationic lipids are one of the most widely used non-viral vectors for the delivery of DNA into cultured cells and are easily synthesized, leading to a large variety of well-characterized molecules. This review discusses strategies for the design of efficient cationic lipids that overcome the critical barriers of in vitro transfection. A particular focus is placed on natural hydrophilic headgroups and lipophilic tails that have been used to synthesize biocompatible and non-toxic cationic lipids. We also present chemical features that have been investigated to enhance the transfection efficiency of cationic lipids by promoting the escape of lipoplexes from the endosomal compartment and DNA release from DNA-liposome complexes. Transfection efficiency studies using these strategies are likely to improve the understanding of the mechanism of cationic lipid-mediated gene delivery and to help the rational design of novel cationic lipids.

  20. Journal of Asian Natural Products Research简介

    Institute of Scientific and Technical Information of China (English)

    李霄茜

    2009-01-01

    @@ Journal of Asian Natural Products Research(,简称JANPR;ISSN:1028-6020;e-ISSN:1477-2213)是由英国Taylor & Francis公司出版发行的一本以亚洲传统医学中天然产品的化学和药理学研究为主要方向的国际性杂志.

  1. Five decades in the study of natural products*

    Indian Academy of Sciences (India)

    T R Govindachari

    2002-06-01

    This paper describes the five-decade long fascinating journey taken by Prof. T R Govindachari towards the study of the natural products of India. A variety of Indian plants were investigated by him for the study of their constituent alkaloids and terpenoids. The concluding part of the paper summarizes the isolation and identification of the constituents of the Neem kernel, which eventually led to the first X-ray structure determination of azadirachtin A.

  2. Cytotoxic Natural Products from Marine Sponge-Derived Microorganisms

    Directory of Open Access Journals (Sweden)

    Huawei Zhang

    2017-03-01

    Full Text Available A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last 62 years from 1955 to 2016, which are assorted into seven types: terpenes, alkaloids, peptides, aromatics, lactones, steroids, and miscellaneous compounds.

  3. Synthesis of carbon nanotubes using natural carbon precursor: Castor oil

    Science.gov (United States)

    Raziah, A. Z.; Junizah, A. R.; Saifuddin, N.

    2012-09-01

    Castor oil has long been an article of commerce due to its versatility as it is widely used as a starting material for many industrial chemical products because of its unique structure. In this study, carbon nanotubes has been synthesized by thermal decomposition of castor oil in nitrogen atmosphere at 300-400δC using custom-made microwave processing unit. The precursor material was catalyzed by iron clusters originating from the addition of ferrocene. The morphology and characterization of the CNTs were studied and discussed by transmission electron microscopy (TEM).

  4. An Update on Natural Products with Carbonic Anhydrase Inhibitory Activity.

    Science.gov (United States)

    Karioti, Anastasia; Carta, Fabrizio; Supuran, Claudiu T

    2016-01-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological processes. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. It is more than 70 years that synthetic compounds, mainly sulfonamides, have been used in clinical practice as diuretics and systemic acting antiglaucoma drugs. Recent studies using natural product libraries and isolated constituents from natural sources (such as fungi and plants) have disclosed novel chemotypes possessing carbonic anhydrase inhibition activities. These natural sources offer new opportunities in the search for new and more effective carbonic anhydrase inhibitors, and may serve as new leads for the design and development of future drugs. This review will discuss the most recent advances in the search of naturally occurring products and their synthetic derivatives that inhibit the CAs and their mechanisms of action at molecular level. Plant extracts are not considered in the present review.

  5. Rationale for a natural products approach to herbicide discovery.

    Science.gov (United States)

    Dayan, Franck E; Owens, Daniel K; Duke, Stephen O

    2012-04-01

    Weeds continue to evolve resistance to all the known modes of herbicidal action, but no herbicide with a new target site has been commercialized in nearly 20 years. The so-called 'new chemistries' are simply molecules belonging to new chemical classes that have the same mechanisms of action as older herbicides (e.g. the protoporphyrinogen-oxidase-inhibiting pyrimidinedione saflufenacil or the very-long-chain fatty acid elongase targeting sulfonylisoxazoline herbicide pyroxasulfone). Therefore, the number of tools to manage weeds, and in particular those that can control herbicide-resistant weeds, is diminishing rapidly. There is an imminent need for truly innovative classes of herbicides that explore chemical spaces and interact with target sites not previously exploited by older active ingredients. This review proposes a rationale for a natural-products-centered approach to herbicide discovery that capitalizes on the structural diversity and ingenuity afforded by these biologically active compounds. The natural process of extended-throughput screening (high number of compounds tested on many potential target sites over long periods of times) that has shaped the evolution of natural products tends to generate molecules tailored to interact with specific target sites. As this review shows, there is generally little overlap between the mode of action of natural and synthetic phytotoxins, and more emphasis should be placed on applying methods that have proved beneficial to the pharmaceutical industry to solve problems in the agrochemical industry.

  6. Natural Products as Source of Potential Dengue Antivirals

    Directory of Open Access Journals (Sweden)

    Róbson Ricardo Teixeira

    2014-06-01

    Full Text Available Dengue is a neglected disease responsible for 22,000 deaths each year in areas where it is endemic. To date, there is no clinically approved dengue vaccine or antiviral for human beings, even though there have been great efforts to accomplish these goals. Several approaches have been used in the search for dengue antivirals such as screening of compounds against dengue virus enzymes and structure-based computational discovery. During the last decades, researchers have turned their attention to nature, trying to identify compounds that can be used as dengue antivirals. Nature represents a vast reservoir of substances that can be explored with the aim of discovering new leads that can be either used directly as pharmaceuticals or can serve as lead structures that can be optimized towards the development of new antiviral agents against dengue. In this review we describe an assortment of natural products that have been reported as possessing dengue antiviral activity. The natural products are organized into classes of substances. When appropriate, structure-activity relationships are outlined. The biological assays used to assess antiviral activity are briefly described.

  7. Novel fermentation processes for manufacturing plant natural products.

    Science.gov (United States)

    Zhou, Jingwen; Du, Guocheng; Chen, Jian

    2014-02-01

    Microbial production of plant natural products (PNPs), such as terpenoids, flavonoids from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. Rapid development of metabolic engineering and synthetic biology of microorganisms shows many advantages to replace the current extraction of these useful high price chemicals from plants. Although few of them were actually applied on a large scale for PNPs production, continuous research on these high-price chemicals and the rapid growing global market of them, show the promising future for the production of these PNPs by microorganisms with a more economic and environmental friendly way. Introduction of novel pathways and optimization of the native cellular processes by metabolic engineering of microorganisms for PNPs production are rapidly expanding its range of cell-factory applications. Here we review recent progress in metabolic engineering of microorganisms for the production of PNPs. Besides, factors restricting the yield improvement and application of lab-scale achievements to industrial applications have also been discussed.

  8. An overview on the potential of natural products as ureas

    Directory of Open Access Journals (Sweden)

    Luzia V. Modolo

    2015-01-01

    Full Text Available Ureases, enzymes that catalyze urea hydrolysis, have received considerable attention for their impact on living organisms’ health and life quality. On the one hand, the persistence of urease activity in human and animal cells can be the cause of some diseases and pathogen infections. On the other hand, food production can be negatively affected by ureases of soil microbiota that, in turn, lead to losses of nitrogenous nutrients in fields supplemented with urea as fertilizer. In this context, nature has proven to be a rich resource of natural products bearing a variety of scaffolds that decrease the ureolytic activity of ureases from different organisms. Therefore, this work compiles the state-of-the-art researches focused on the potential of plant natural products (present in extracts or as pure compounds as urease inhibitors of clinical and/or agricultural interests. Emphasis is given to ureases of Helicobacter pylori, Canavalia ensiformis and soil microbiota although the active site of this class of hydrolases is conserved among living organisms.

  9. Automated genome mining of ribosomal peptide natural products

    Energy Technology Data Exchange (ETDEWEB)

    Mohimani, Hosein; Kersten, Roland; Liu, Wei; Wang, Mingxun; Purvine, Samuel O.; Wu, Si; Brewer, Heather M.; Pasa-Tolic, Ljiljana; Bandeira, Nuno; Moore, Bradley S.; Pevzner, Pavel A.; Dorrestein, Pieter C.

    2014-07-31

    Ribosomally synthesized and posttranslationally modified peptides (RiPPs), especially from microbial sources, are a large group of bioactive natural products that are a promising source of new (bio)chemistry and bioactivity (1). In light of exponentially increasing microbial genome databases and improved mass spectrometry (MS)-based metabolomic platforms, there is a need for computational tools that connect natural product genotypes predicted from microbial genome sequences with their corresponding chemotypes from metabolomic datasets. Here, we introduce RiPPquest, a tandem mass spectrometry database search tool for identification of microbial RiPPs and apply it for lanthipeptide discovery. RiPPquest uses genomics to limit search space to the vicinity of RiPP biosynthetic genes and proteomics to analyze extensive peptide modifications and compute p-values of peptide-spectrum matches (PSMs). We highlight RiPPquest by connection of multiple RiPPs from extracts of Streptomyces to their gene clusters and by the discovery of a new class III lanthipeptide, informatipeptin, from Streptomyces viridochromogenes DSM 40736 as the first natural product to be identified in an automated fashion by genome mining. The presented tool is available at cy-clo.ucsd.edu.

  10. Antimycobacterial natural products--an opportunity for the Colombian biodiversity.

    Science.gov (United States)

    Bueno, Juan; Coy, Ericsson David; Stashenko, Elena

    2011-12-01

    It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug-resistance. For over 50 years, natural products have served us well on combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites have helped to double our life span, reduced pain and suffering, and revolutionized medicine. Colombia is a megadiverse country with enormous potential to offer leads for new antimycobacterial drugs. The principal aim of this article is to show a state of the art on antimycobacterial natural products research in Colombia compared to the rest of the world, in order to develop programs for bioprospecting with a view to determining the biological activity for pharmaceutical and industrial application of natural products in our country.

  11. Natural products research in South Africa: 1890–2010

    Directory of Open Access Journals (Sweden)

    Siegfried E. Drewes

    2012-05-01

    Full Text Available Having spent some 50 years as an organic chemist with an interest in medicinal plant chemistry in South Africa it was relevant now to ask three questions, (1 when were natural products first utilised, (2 who were the people involved, and (3 what is the status quo? Based on older literature published in the South African Journal of Chemistry, information gleaned from attendance at innumerable chemistry conferences, and relevant literature in university archives, a great deal of information was gathered to answer the first two questions. For example, that the first veterinarian to treat cattle diseases caused by poisonous plants in the Eastern Cape was Dr Jotella Soga in the 1890s. Contributions from other prominent scientists such as Marais, Rindl, Rimington and Warren followed. From about 1940 to the 1990s, researchers concentrated mainly on the isolation of new compounds from local plants for which some indigenous knowledge was recorded. Foreign chemists also arrived and did a fair amount of ‘exploitation’ of natural products. Thus, the anti-cancer compound combretastatin was first isolated from the indigenous tree Combretum caffrum. Plant chemistry in South Africa has blossomed in the last decade, with many students from previously disadvantaged backgrounds, but with a keen interest in muti or medicinal chemistry, entering the field. Recent findings have rekindled the belief that a major development in natural products would at last emerge from Africa.

  12. Natural gas production problems : solutions, methodologies, and modeling.

    Energy Technology Data Exchange (ETDEWEB)

    Rautman, Christopher Arthur; Herrin, James M.; Cooper, Scott Patrick; Basinski, Paul M. (El Paso Production Company, Houston, TX); Olsson, William Arthur; Arnold, Bill Walter; Broadhead, Ronald F. (New Mexico Bureau of Geology and Mineral Resources, Socorro, NM); Knight, Connie D. (Consulting Geologist, Golden, CO); Keefe, Russell G.; McKinney, Curt (Devon Energy Corporation, Oklahoma City, OK); Holm, Gus (Vermejo Park Ranch, Raton, NM); Holland, John F.; Larson, Rich (Vermejo Park Ranch, Raton, NM); Engler, Thomas W. (New Mexico Institute of Mining and Technology, Socorro, NM); Lorenz, John Clay

    2004-10-01

    Natural gas is a clean fuel that will be the most important domestic energy resource for the first half the 21st centtuy. Ensuring a stable supply is essential for our national energy security. The research we have undertaken will maximize the extractable volume of gas while minimizing the environmental impact of surface disturbances associated with drilling and production. This report describes a methodology for comprehensive evaluation and modeling of the total gas system within a basin focusing on problematic horizontal fluid flow variability. This has been accomplished through extensive use of geophysical, core (rock sample) and outcrop data to interpret and predict directional flow and production trends. Side benefits include reduced environmental impact of drilling due to reduced number of required wells for resource extraction. These results have been accomplished through a cooperative and integrated systems approach involving industry, government, academia and a multi-organizational team within Sandia National Laboratories. Industry has provided essential in-kind support to this project in the forms of extensive core data, production data, maps, seismic data, production analyses, engineering studies, plus equipment and staff for obtaining geophysical data. This approach provides innovative ideas and technologies to bring new resources to market and to reduce the overall environmental impact of drilling. More importantly, the products of this research are not be location specific but can be extended to other areas of gas production throughout the Rocky Mountain area. Thus this project is designed to solve problems associated with natural gas production at developing sites, or at old sites under redevelopment.

  13. Microbial production of fructosyltransferases for synthesis of pre-biotics.

    Science.gov (United States)

    Maiorano, Alfredo Eduardo; Piccoli, Rosane Moniz; da Silva, Elda Sabino; de Andrade Rodrigues, Maria Filomena

    2008-11-01

    Fructooligosaccharides (FOS) are prebiotic substances found in several vegetable or natural foods. The main commercial production of FOS comes from enzymatic transformation of sucrose by the microbial enzyme fructosyltransferase. The development of more efficient enzymes, with high activity and stability, is required and this has attracted the interest of biotechnologists and microbiologists with production by several microorganisms being studied. This article reviews and discusses FOS chemical structure, enzyme characteristics, the nomenclature, producer microorganisms and enzyme production both in solid state fermentation and submerged cultivation.

  14. 76 FR 19996 - Cooperative Agreement With the University of Mississippi's National Center for Natural Products...

    Science.gov (United States)

    2011-04-11

    ... National Center for Natural Products Research (U01) To Develop and Disseminate Botanical Natural Product... and dissemination of natural products research and science and the programs developed under the... develop and disseminate botanical natural product research with an emphasis on public safety according...

  15. Enhancement of dimethylsulfide production by anoxic stress in natural seawater

    Science.gov (United States)

    Omori, Yuko; Tanimoto, Hiroshi; Inomata, Satoshi; Wada, Shigeki; Thume, Kathleen; Pohnert, Georg

    2015-05-01

    Dimethylsulfide (DMS) is produced by phytoplankton in the ocean and plays an important role in biogeochemical cycles and climate system of the Earth. Previous field studies reported a possible relationship between DMS enhancement and anoxic condition, although the governing processes are still to be identified. Here we show the first direct evidence for the enhancement of DMS production by natural planktonic assemblages caused by anoxic stress. Under the anoxic condition, DMS production was considerably enhanced and DMS bacterial consumption was inhibited, resulting in an eightfold higher rate of gross DMS production than that under the oxic condition. Our results demonstrated that anoxic stress is one of important "environmental factors" in the marine DMS dynamics, suggesting the possible global importance due to ubiquity of anoxic conditions in the coastal oceans. This process would become more important in the future due to expansion of coastal hypoxic and anoxic zones by global warming.

  16. Natural synthesis of bioactive greigite by solid-gas reactions

    Science.gov (United States)

    Igarashi, Kensuke; Yamamura, Yasuhisa; Kuwabara, Tomohiko

    2016-10-01

    Greigite, a ferrimagnetic iron sulfide Fe(II)Fe(III)2S4, is thought to have played an essential role in chemical evolution leading to the origin of life. Greigite contains a [4Fe-4S] cluster-like structure and has been synthesized in the laboratory by liquid-state reactions. However, it is unclear how greigite can be synthesized in nature. Herein, we show that greigite is synthesized by the solid-gas reaction of Fe(III)-oxide-hydroxides and H2S. We discovered that the hyperthermophilic hydrogenotrophic methanogen Methanocaldococcus jannaschii reduced elemental sulfur, and the resulting sulfide generated greigite from hematite. The time course and pH dependence of the reaction respectively indicated the involvement of amorphous FeS and H2S as reaction intermediates. An abiotic solid-gas reaction of hematite and H2S (g) under strictly anaerobic conditions was developed. The solid-gas reaction fully converted hematite to greigite/pyrite at 40-120 °C within 12 h and was unaffected by the bulk gas phase. Similar abiotic reactions occurred, but relatively slowly, with aqueous H2S in acidulous liquids using hematite, magnetite, or amorphous FeO(OH) as starting materials, suggesting that greigite was extensively produced in the Hadean Eon as these Fe(III)-oxide-hydroxides were shown to be present or routinely produced during that era. Surprisingly, the obtained greigite induced methanogenesis and growth of hydrogenotrophic methanogens, suggesting that the external greigite crystals enhanced reactions that would otherwise require enzymes, such as [4Fe-4S] cluster-harboring membrane-bound hydrogenases. These data suggested that the greigite produced by the solid-gas and solid-dissolved gas reactions was bioactive.

  17. Contrast-negation and texture synthesis differentially disrupt natural texture appearance

    Directory of Open Access Journals (Sweden)

    Benjamin J Balas

    2012-11-01

    Full Text Available Natural textures have characteristic image statistics that make them discriminable from unnatural textures. For example, both contrast-negation and texture synthesis alter the appearance of natural textures even though each manipulation preserves some features while disrupting others. Here, we examined the extent to which contrast-negation and texture synthesis each introduce or remove critical perceptual features for discriminating unnatural textures from natural textures. We find that both manipulations remove information that observers use for distinguishing natural textures from transformed versions of the same patterns, but do so in different ways. Texture synthesis removes information that is relevant for discrimination in both abstract patterns and ecologically valid textures, and we also observe a category-dependent asymmetry for identifying an oddball real texture among synthetic distractors. Contrast negation exhibits no such asymmetry, and also does not impact discrimination performance in abstract patterns. We discuss our results in the context of the visual system’s tuning to ecologically relevant patterns and other results describing sensitivity to higher-order statistics in texture patterns.

  18. Protein structure similarity clustering (PSSC) and natural product structure as inspiration sources for drug development and chemical genomics.

    Science.gov (United States)

    Dekker, Frank J; Koch, Marcus A; Waldmann, Herbert

    2005-06-01

    Finding small molecules that modulate protein function is of primary importance in drug development and in the emerging field of chemical genomics. To facilitate the identification of such molecules, we developed a novel strategy making use of structural conservatism found in protein domain architecture and natural product inspired compound library design. Domains and proteins identified as being structurally similar in their ligand-sensing cores are grouped in a protein structure similarity cluster (PSSC). Natural products can be considered as evolutionary pre-validated ligands for multiple proteins and therefore natural products that are known to interact with one of the PSSC member proteins are selected as guiding structures for compound library synthesis. Application of this novel strategy for compound library design provided enhanced hit rates in small compound libraries for structurally similar proteins.

  19. Magnesium carbide synthesis from methane and magnesium oxide - a potential methodology for natural gas conversion to premium fuels and chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, A.F.; Modestino, A.J.; Howard, J.B. [Massachusetts Institute of Technology, Cambridge, MA (United States)] [and others

    1995-12-31

    Diversification of the raw materials base for manufacturing premium fuels and chemicals offers U.S. and international consumers economic and strategic benefits. Extensive reserves of natural gas in the world provide a valuable source of clean gaseous fuel and chemical feedstock. Assuming the availability of suitable conversion processes, natural gas offers the prospect of improving flexibility in liquid fuels and chemicals manufacture, and thus, the opportunity to complement, supplement, or displace petroleum-based production as economic and strategic considerations require. The composition of natural gas varies from reservoir to reservoir but the principal hydrocarbon constituent is always methane (CH{sub 4}). With its high hydrogen-to-carbon ratio, methane has the potential to produce hydrogen or hydrogen-rich products. However, methane is a very chemically stable molecule and, thus, is not readily transformed to other molecules or easily reformed to its elements (H{sub 2} and carbon). In many cases, further research is needed to augment selectivity to desired product(s), increase single-pass conversions, or improve economics (e.g. there have been estimates of $50/bbl or more for liquid products) before the full potential of these methodologies can be realized on a commercial scale. With the trade-off between gas conversion and product selectivity, a major challenge common to many of these technologies is to simultaneously achieve high methane single-pass conversions and high selectivity to desired products. Based on the results of the scoping runs, there appears to be strong indications that a breakthrough has finally been achieved in that synthesis of magnesium carbides from MgO and methane in the arc discharge reactor has been demonstrated.

  20. Characterization of rapidly and naturally quenched skeletal iron catalysts for FT synthesis

    Institute of Scientific and Technical Information of China (English)

    YAN Shi-run; QIAO Ming-hua; ZHU Yuan-long; FAN Kang-nian

    2004-01-01

    The slurry phase is a promising system for Fischer-Tropsch (FT) synthesis. Since the liquid medium efficiently removes the heat of reaction so that the steady-state reaction is easily achieved. High catalytic activity is maintained due to removal of waxy products from the catalyst surface by the action of solvent. In addition, CO-rich syngas from coal gasification can be directly used in FT synthesis which may increase the thermal efficiency of the indirect coal liquefaction. One of the important problems to be solved for slurry phase FT is the catalyst attrition and separation from wax residue. Fused iron and Raney iron were found to have high attrition resistance and easy to separate from wax in slurry phase FT synthesis, but their activity is relatively low. Amorphous alloys made by rapid quenching techniques have drawn increasing interest due to their superior mechanical,chemical and magnetic properties compared to the thermodynamically stable crystalline alloys of the same compositions. It is reported that rapidly quenched skeletal Ni catalyst showed higher catalytic activity than Raney Ni in selective hydrogenation of unsaturated organic functional groups.In this paper, Fe50Al50 (by weight) alloys with different quenching rates, rapid quenching (RQ) and natural quenching (NQ) were prepared for FT synthesis. The phase composition of alloys was characterized by XRD. The physical properties, thermal-stability and adsorption properties of skeletal Fe that was prepared by leaching aluminum of the corresponding alloy with aqueous solution of NaOH were also studied by BET, in situ XRD and H2- and CO-TPD. It is found from XRD patterns of the alloys that RQ Fe50Al50 is composed of orthorhombic phase, and NQ Fe50Al50 alloy is mainly composed of monoclinic phase. Meanwhile, diffraction peaks of the RQ alloy are seriously broadened. After leaching aluminum by aqueous solution of NaOH at the same conditions,skeletal Fe from the RQ alloy give the higher specific surface

  1. Combinatorial synthesis by nature: volatile organic sulfur-containing constituents of Ruta chalepensis L.

    Science.gov (United States)

    Escher, Sina; Niclass, Yvan; van de Waal, Matthijs; Starkenmann, Christian

    2006-09-01

    Ongoing interest in discovering new natural fragrance and flavor ingredients prompted us to examine a solvent extract of sulfurous-sweaty smelling Ruta chalepensis L. (Rutaceae) plant material more closely. Twenty-one sulfur-containing constituents of similar structures were identified by GC/MS techniques. Amongst them, 14 have never been described to occur in nature. The compounds 1-18 belong to a family of natural flavor and fragrance molecules having a 1,3-positioned O,S moiety in common. The identities of the natural constituents were confirmed by comparison with synthetic reference samples, and the organoleptic properties of the latter were studied. The relative and absolute configurations of the four stereoisomers of 4-methyl-3-sulfanylhexan-1-ol (5) were established by stereoselective synthesis. The natural isomers consisted of a 65 : 35 mixture of (3R,4S)-5 and (3S,4S)-5.

  2. Production of hydrogen by thermocatalytic cracking of natural gas

    Energy Technology Data Exchange (ETDEWEB)

    Muradov, N. [Florida Solar Energy Center, Cocoa, FL (United States)

    1996-10-01

    The conventional methods of hydrogen production from natural gas (for example, steam reforming and partial oxidation) are complex, multi-step processes that produce large quantities of CO{sub 2}. The main goal of this project is to develop a technologically simple process for hydrogen production from natural gas (NG) and other hydrocarbon fuels via single-step decomposition of hydrocarbons. This approach eliminates or significantly reduces CO{sub 2} emission. Carbon is a valuable by-product of this process, whereas conventional methods of hydrogen production from NG produce no useful by-products. This approach is based on the use of special catalysts that reduce the maximum temperature of the process from 1400-1500{degrees}C (thermal non-catalytic decomposition of methane) to 500-900{degrees}C. Transition metal based catalysts and various forms of carbon are among the candidate catalysts for the process. This approach can advantageously be used for the development of compact NG reformers for on-site production of hydrogen-methane blends at refueling stations and, also, for the production of hydrogen-rich gas for fuel cell applications. The author extended the search for active methane decomposition catalysts to various modifications of Ni-, Fe-, Mo- and Co-based catalysts. Variation in the operational parameters makes it possible to produce H{sub 2}-CH{sub 4} blends with a wide range of hydrogen concentrations that vary from 15 to 98% by volume. The author found that Ni-based catalysts are more effective at temperatures below 750{degrees}C, whereas Fe-based catalysts are effective at temperatures above 800{degrees}C for the production of hydrogen with purity of 95% v. or higher. The catalytic pyrolysis of liquid hydrocarbons (pentane, gasoline) over Fe-based catalyst was conducted. The author observed the production of a hydrogen-rich gas (hydrogen concentration up to 97% by volume) at a rate of approximately 1L/min.mL of hydrocarbon fuel.

  3. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya

    2014-09-01

    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  4. Polyphenols-rich natural products for treatment of diabetes.

    Science.gov (United States)

    Dragan, S; Andrica, F; Serban, Maria-Corina; Timar, R

    2015-01-01

    Currently, experimental and clinical evidences showed that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities in type 2 diabetes mellitus (DM), due to their biological properties. Natural products modulate the carbohydrate metabolism by various mechanisms, such as restoring beta-cells integrity and physiology, enhancing insulin releasing activity, and the glucose using. Sea buckthorn berries, red grapes, bilberries, chokeberries and popular drinks like cocoa, coffee and green tea are all rich in polyphenols and may decrease the insulin response, offer in g a natural alternative of treatment in diabetes. Therefore, researches are now focused on potential efficacies of different types of polyphenols, including flavonoids, phenolic acids, lignans, anthocyans and stilbenes. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia and insulin resistance, increase lipid metabolism and optimize oxidative stress and inflammatory processes. It is important to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.

  5. Natural products as potential cancer therapy enhancers: A preclinical update.

    Science.gov (United States)

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran; Mahajna, Jamal

    2014-01-01

    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  6. Improved pinocembrin production in Escherichia coli by engineering fatty acid synthesis.

    Science.gov (United States)

    Cao, Weijia; Ma, Weichao; Zhang, Bowen; Wang, Xin; Chen, Kequan; Li, Yan; Ouyang, Pingkai

    2016-04-01

    The development of efficient microbial processes for pinocembrin production has attracted considerable attention. However, pinocembrin biosynthetic efficiency is greatly limited by the low availability of the malonyl-CoA cofactor in Escherichia coli. Fatty acid biosynthesis is the only metabolic process in E. coli that consumes malonyl-CoA; therefore, we overexpressed the fatty acid biosynthetic pathway enzymes β-ketoacyl-ACP synthase III (FabH) and β-ketoacyl-ACP synthase II (FabF) alone and in combination, and investigated the effect on malonyl-CoA. Interestingly, overexpressing FabH, FabF or both enzymes in E. coli BL21 (DE3) decreased fatty acid synthesis and increased cellular malonyl-CoA levels 1.4-, 1.6-, and 1.2-fold, respectively. Furthermore, pinocembrin production was increased 10.6-, 31.8-, and 5.87-fold in recombinant strains overexpressing FabH, FabF and both enzymes, respectively. Overexpression of FabF, therefore, triggered the highest pinocembrin production and malonyl-CoA levels. The addition of cerulenin further increased pinocembrin production in the FabF-overexpressing strain, from 25.8 to 29.9 mg/L. These results demonstrated that overexpressing fatty acid synthases can increase malonyl-CoA availability and improve pinocembrin production in a recombinant E. coli host. This strategy may hold promise for the production of other important natural products in which cellular malonyl-CoA is rate limiting.

  7. Entotheonella Bacteria as Source of Sponge-Derived Natural Products: Opportunities for Biotechnological Production.

    Science.gov (United States)

    Bhushan, Agneya; Peters, Eike E; Piel, Jörn

    2017-01-01

    Marine sponges belong to the oldest animals existing today. Apart from their role in recycling of carbon and nitrogen in the ocean, they are also an important source of a wide variety of structurally diverse bioactive natural products. Over the past few decades, a multitude of compounds from sponges have been discovered exhibiting diverse, pharmacologically promising activities. However, in many cases the low substance quantities present in the sponge tissue would require the collection of large amounts of sponge material, thus impeding further drug development. Recent research has focused on understanding natural product biosynthesis in sponges and on investigating symbiotic bacteria as possible production sources in order to develop sustainable production systems. This chapter covers research efforts that have taken place over the past few years involving the identification of 'Entotheonella' symbionts responsible for production of sponge compounds, as well as the elucidation of their biosynthetic routes, highlighting future biotechnological applications.

  8. Water for wood products versus nature, food or feed

    Science.gov (United States)

    Schyns, Joep; Booij, Martijn; Hoekstra, Arjen

    2017-04-01

    more water available for the generation of other ecosystem services. Our findings contribute to a more complete picture of the human appropriation of water and the understanding of the interlinkages between the SDGs, thus feeding the debate on water for wood products versus nature, food or feed.

  9. Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids.

    Science.gov (United States)

    Fichna, Jakub; Lewellyn, Kevin; Yan, Feng; Roth, Bryan L; Zjawiony, Jordan K

    2011-01-01

    The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents for binding affinity of salvinorin A derivatives.

  10. Synthesis And Application Of Natural Polymeric Plasticizer Obtained Through Polyesterification Of Rice Fatty Acid

    OpenAIRE

    Vieira, MGA; da Silva, MA; Macumoto, ACG; dos Santos, LO; Beppu, Mm

    2014-01-01

    This study includes the synthesis of a new natural plasticizer obtained through esterification reaction of rice fatty acid and polyols, its physicochemical characterization and its preliminary application in polyvinyl chloride (PVC). Monopropylene glycol, octanol and diethylene glycol were used as polyols for esterification reaction. Catalyst Fascat (R) 4100, was also added. Viscosity, acidity and hydroxyl index, moisture content, molar mass, chemical composition (by FTIR) and color were dete...

  11. Environmental review of natural gas production in Lake Erie

    Energy Technology Data Exchange (ETDEWEB)

    O' Shea, K. [Dillon Consulting Ltd., Cambridge, ON (Canada)

    2002-07-01

    The water of Lake Erie is used as a source of drinking water for Ontario, New York, Pennsylvania, Ohio and Michigan. An environmental review has been conducted to determine the impact of drilling operations on the overall ecology of the lake. Since 1913, 2000 natural gas wells have been drilled in Lake Erie, of which 550 currently produce gas and account for 75 per cent of Ontario's total gas production. 180 wells are shut-in or suspended and the remaining wells have been abandoned. The gas wells are connected to onshore production facilities by approximately 1,600 km of small diameter pipelines that lie buried near shore or on top of the lake bed. Nearly 90 per cent of the in-lake infrastructure is in water depths of more than 20 metres. Talisman Energy is actively involved with the Canadian Coast Guard, the Department of Fisheries and Oceans, and the Ministry of Natural Resources to ensure cooperation between regulators and off-shore personnel. The environmental assessment of natural gas production in Lake Erie included a review of regulatory and best management practices, a biophysical overview of the lake, and a review of drilling practices, well completions, handling of waste streams, materials management, operations inspections, wastewater discharge, air emissions, and oil spills. It was revealed that for most drilling programs, cuttings are washed and discharged to the Lake. Ongoing testing will determine the impact that this practice has on benthic populations. The drill muds used for drilling operations are water based, environmentally friendly, and re-used between well locations. For completion programs, all well activities are closed circuit operations. Wells are abandoned through plugging with cement, removing wellheads and casing below the lake bottom. There has been a reported volume of about 23,000 litres of spilled product from 1990 to 2001, of which 68 per cent has come from 3 industrial companies that operate near Lake Erie. The offshore gas

  12. Bioactive Natural Products of Marine Sponges from the Genus Hyrtios

    Directory of Open Access Journals (Sweden)

    Nourhan Hisham Shady

    2017-05-01

    Full Text Available Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.

  13. A general enantioselective route to the chamigrene natural product family

    KAUST Repository

    White, David E.

    2010-06-01

    Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

  14. NMR structural studies of oligosaccharides and other natural products

    DEFF Research Database (Denmark)

    Kjærulff, Louise

    produce secondary metabolites for signaling and competing against other organisms, and these molecules are important in drug discovery due to their inherent biological activities. From a marine Photobacterium (P. halotolerans) we isolated the solonamides and the ngercheumicins, two families of cyclic....... fijiensis, was also investigated for production of novel secondary metabolites, and a new pyranonigrin (E) was isolated and structure elucidated by NMR spectroscopy along with JBIR-74 and decumbenone A, two known metabolites previously isolated from Aspergillus and Penicillium species. Oligosaccharides...... with respect to n+1JHH between these two experiments, observed in the nJCH HMBC cross peak. Through a double editing procedure this enables straightforward determination of both sign and magnitude of n+1JHH, including for very small coupling constants. Excellent results were obtained for the natural product...

  15. Natural products from Bacillus subtilis with antimicrobial properties☆

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Yafei Liang; Mianbin Wu; Zhengjie Chen; Jianping Lin; Lirong Yang

    2015-01-01

    Bacil us subtilis produces many chemical y-diverse secondary metabolites of interest to chemists and biologists. Based on this, this review gives a detalled overview of the natural components produced by B. subtilis including cyclic lipopeptides, polypeptides, proteins (enzymes), and non-peptide products. Their structures, bioactive ac-tivities and the relevant variants as novel lead structures for drug discovery are also described. The challenging effects of fermentation metabolites, isolation and purification, as wel as the overproduction of bioactive com-pounds from B. subtilis by metabolic engineering, were also highlighted. Systematical y exploring biosynthetic routes and the functions of secondary metabolites from B. subtilis may not only be beneficial in improving yields of the products, but also in helping them to be used in food industry and public medical service on a large-scale.

  16. Natural Dietary and Herbal Products in Anti-Obesity Treatment.

    Science.gov (United States)

    Sun, Nan-Nong; Wu, Tsung-Yen; Chau, Chi-Fai

    2016-10-11

    The prevalence of overweight and obesity is on the rise around the world. Common comorbidities associated with obesity, particularly diabetes, hypertension, and heart disease have an impact on social and financial systems. Appropriate lifestyle and behavior interventions are still the crucial cornerstone to weight loss success, but maintaining such a healthy lifestyle is extremely challenging. Abundant natural materials have been explored for their obesity treatment potential and widely used to promote the development of anti-obesity products. The weight loss segment is one of the major contributors to the overall revenue of the dietary supplements market. In this review, the anti-obesity effects of different dietary or herbal products, and their active ingredients and mechanisms of action against obesity will be discussed.

  17. The snowmaker: nature identical snow production in the laboratory

    Science.gov (United States)

    Schleef, S.; Jaggi, M.; Loewe, H.; Schneebeli, M.

    2013-12-01

    Using natural snow for laboratory experiments can be tricky due to shortage of winter periods and snowfall, difficulties of sample casting and transport, and the great variability of natural snow due to the varying conditions of crystal growth in the clouds. This hinders repeatable laboratory experiments with reproducible specimen and microstructural characteristics. To minimize experimental uncertainties we designed an improved machine called snowmaker, which enables us to produce nature-identical snow in a cold laboratory under well defined conditions. The snowmaker is based on well-known principles: warm humid air from a heated water basin is advected into a cold nucleation chamber where the vapor resublimates on stretched Nylon wires. Crystals are automatically harvested by a motor driven brush rack and collected in a box, thereby several kilograms of snow can be produced per day with minimum maintenance. The excess vapor is collected in a moisture trap to avoid frost in the laboratory. The entire construction is designed as a rolling, modular assembly system which can easily carried out of the laboratory for defrosting. In addition to previous attempts we focus on the reproducibility of the samples and the comparison to natural snow down to the microscale. We show that the settings of water temperature and cold laboratory temperature facilitates the production of different crystal shapes like dendrites and needles in a reproducible way. Besides photography, we analyzed the microstructure of snowmaker crystals in aggregated specimen by X-ray microtomography. Depending on the settings we can create reproducible samples with density of 50-170 kg/m3 and specific surface areas of 50-80 mm-1. We briefly touch similarities between artificial and natural snow samples with respect to crystal habit, microstructural parameters and short-time metamorphism.

  18. US production of natural gas from tight reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    1993-10-18

    For the purposes of this report, tight gas reservoirs are defined as those that meet the Federal Energy Regulatory Commission`s (FERC) definition of tight. They are generally characterized by an average reservoir rock permeability to gas of 0.1 millidarcy or less and, absent artificial stimulation of production, by production rates that do not exceed 5 barrels of oil per day and certain specified daily volumes of gas which increase with the depth of the reservoir. All of the statistics presented in this report pertain to wells that have been classified, from 1978 through 1991, as tight according to the FERC; i.e., they are ``legally tight`` reservoirs. Additional production from ``geologically tight`` reservoirs that have not been classified tight according to the FERC rules has been excluded. This category includes all producing wells drilled into legally designated tight gas reservoirs prior to 1978 and all producing wells drilled into physically tight gas reservoirs that have not been designated legally tight. Therefore, all gas production referenced herein is eligible for the Section 29 tax credit. Although the qualification period for the credit expired at the end of 1992, wells that were spudded (began to be drilled) between 1978 and May 1988, and from November 5, 1990, through year end 1992, are eligible for the tax credit for a subsequent period of 10 years. This report updates the EIA`s tight gas production information through 1991 and considers further the history and effect on tight gas production of the Federal Government`s regulatory and tax policy actions. It also provides some high points of the geologic background needed to understand the nature and location of low-permeability reservoirs.

  19. Bacterial Glycosyltransferases: Challenges and opportunities of a highly diverse enzyme class toward tailoring natural products

    Directory of Open Access Journals (Sweden)

    Jochen eSchmid

    2016-02-01

    Full Text Available The enzyme subclass of glycosyltransferases (EC 2.4 currently comprises 97 families as specified by CAZy classification. One of their important roles is in the biosynthesis of disaccharides, oligosaccharides and polysaccharides by catalyzing the transfer of sugar moieties from activated donor molecules to other sugar molecules. In addition glycosyltransferases also catalyze the transfer of sugar moieties onto aglycons, which is of great relevance for the synthesis of many high value natural products. Bacterial glycosyltransferases show a higher sequence similarity in comparison to mammalian ones. Even when most glycosyltransferases are poorly explored, state of the art technologies, such as protein engineering, domain swapping or computational analysis strongly enhance our understanding and utilization of these very promising classes of proteins. This perspective article will focus on bacterial glycosyltransferases, especially on classification, screening and engineering strategies to alter substrate specificity. The future development in these fields as well as obstacles and challenges will be highlighted and discussed.

  20. The Root Growth-Regulating Brevicompanine Natural Products Modulate the Plant Circadian Clock.

    Science.gov (United States)

    de Montaigu, Amaury; Oeljeklaus, Julian; Krahn, Jan H; Suliman, Mohamed N S; Halder, Vivek; de Ansorena, Elisa; Nickel, Sabrina; Schlicht, Markus; Plíhal, Ondřej; Kubiasová, Karolina; Radová, Lenka; Kracher, Barbara; Tóth, Réka; Kaschani, Farnusch; Coupland, George; Kombrink, Erich; Kaiser, Markus

    2017-06-16

    Plant growth regulating properties of brevicompanines (Brvs), natural products of the fungus Penicillium brevicompactum, have been known for several years, but further investigations into the molecular mechanism of their bioactivity have not been performed. Following chemical synthesis of brevicompanine derivatives, we studied their activity in the model plant Arabidopsis by a combination of plant growth assays, transcriptional profiling, and numerous additional bioassays. These studies demonstrated that brevicompanines cause transcriptional misregulation of core components of the circadian clock, whereas other biological read-outs were not affected. Brevicompanines thus represent promising chemical tools for investigating the regulation of the plant circadian clock. In addition, our study also illustrates the potential of an unbiased -omics-based characterization of bioactive compounds for identifying the often cryptic modes of action of small molecules.

  1. The Impending Renaissance in Discovery & Development of Natural Products.

    Science.gov (United States)

    Pawar, Sandip V; Ho, Joe C H; Yadav, Ganapati D; Yadav, Vikramaditya G

    2017-01-01

    Antibiotics are wonder drugs. Unfortunately, owing to overuse, antibiotic resistance is now a serious problem. Society now finds itself in the post-antibiotic era, and the threat of infectious diseases is on the rise. New antibiotics are sorely needed. There is strong evidence that suggests natural products are an attractive source of new antimicrobials. They posses desirable structural and chemical properties that make them potent thearpeutics. However, steep tehnological challenges associated with screening and manufacturing these molecules has stifled the discovery, development and marketing of new antimicrobials. To this end, two recent scientific developments are poised to redress this situation. The recent development of metagenomics and ancillary high-throughput screening technologies has exponentiated the volume of useful genetic sequence information that can be screened for antimicrobial discovery. These approaches have been instrumental in the discovery of new antibiotics from soil and marine environments. Secondly, a new manufacturing paradigm employing metabolic engineering as its engine has greatly accelerated the path to market for these molecules, in addition to improving the atom and energy economy of antimicrobial manufacturing. We outine these developments in this review, and provide a perspective on integrating next-generation approaches such as metagenomics and metabolic engineering with traditional methodologies for discovering and manufacturing antimicrobial natural products in order to unleash a rennaissance in the discovery and development of antimicrobials.

  2. The potential of natural products for targeting PPARα

    Directory of Open Access Journals (Sweden)

    Daniela Rigano

    2017-07-01

    Full Text Available Peroxisome proliferator activated receptors (PPARs α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.

  3. Paraptosis in the anti-cancer arsenal of natural products.

    Science.gov (United States)

    Lee, Dongjoo; Kim, In Young; Saha, Sharmistha; Choi, Kyeong Sook

    2016-06-01

    Given the problems with malignant cancer cells showing innate and acquired resistance to apoptosis, we need alternative means to induce cell death in cancer. Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Although relatively little is known regarding the molecular basis of paraptosis, the underlying mechanism clearly differs from that of apoptosis. Recent studies have shown that various natural products, including curcumin, celastrol, 15d-PGJ2, ophiobolin A, and paclitaxel, demonstrate anti-cancer effects by inducing the paraptosis-associated cell death, which was commonly characterized by vacuolation derived from the ER. Perturbation of cellular proteostasis due to proteasomal inhibition and disruption of sulfhydryl homeostasis, generation of reactive oxygen species, and/or imbalanced homeostasis of ions (e.g., Ca(2+) and K(+)) appear to contribute to the accumulation of misfolded protein and proteotoxicity in this process. Given the pathophysiological importance of paraptosis and the debate regarding the importance of apoptosis in solid tumor, we need to collect the available knowledge regarding paraptosis and suggest future directions in the field. Here, we review the morphological and biochemical features of paraptosis, the natural products that induce paraptosis-associated cell death, their proposed mechanisms, and the significance of paraptosis as a potential anti-cancer strategy. Such work and future clarifications should enable the development of new strategies for preventing cancer and/or combating malignant cancer.

  4. Systems biology approaches to understand natural products biosynthesis

    Directory of Open Access Journals (Sweden)

    Cuauhtemoc eLicona-Cassani

    2015-12-01

    Full Text Available Actinomycetes populate soils and aquatic sediments which impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams and terpenes are well known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed towards a shift in the exploitation of actinomycetes biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets.

  5. Prevention of microbial communities: novel approaches based natural products.

    Science.gov (United States)

    Mogosanu, George D; Grumezescu, Alexandru M; Huang, Keng-Shiang; Bejenaru, Ludovic E; Bejenaru, Cornelia

    2015-01-01

    Firmly attached to different living or non-living, solid or fluid surfaces rich in nutrients and moisture, microbial biofilm is a matter of great interest due to its major importance for the healthcare community. Depending on common strategies such as mutual protection and hibernation (quiescent bacteria), the resistance, survival and virulence of microbial communities have large implications for human pathology, clinical environment and biomedical devices. The microbial biofilm is continuously changing, stimulating inflammation, increasing vascular permeability and preventing the action of macrophages. About 80% of human infections affecting the gastrointestinal, genitourinary and respiratory systems, oral mucosa and teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms. Therefore, the search for modern strategies is even more important as microbial biofilms resistant to conventional antibiotics, antiseptics and disinfectants are involved in the frequent treatment failures of some chronic inflammatory diseases and wounds. Natural products containing secondary metabolites, such as aromatic compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for the prophylaxis and treatment of chronic infections. Surface modification of medical devices with non-polar functionalized nanoparticles stabilizes the natural compounds antibiofilm activity and inhibits microbial adhesion and biofilm formation and growth for a longer period of time. In this regard, an interdisciplinary approach is needed due to the large number of natural derivatives alone or in combination with biocompatible and biodegradable micro-/ nano-engineered materials.

  6. Probiotics stimulate production of natural antibodies in chickens.

    Science.gov (United States)

    Haghighi, Hamid R; Gong, Jianhua; Gyles, Carlton L; Hayes, M Anthony; Zhou, Huaijun; Sanei, Babak; Chambers, James R; Sharif, Shayan

    2006-09-01

    Commensal bacteria in the intestine play an important role in the development of immune response. These bacteria interact with cells of the gut-associated lymphoid tissues (GALT). Among cells of the GALT, B-1 cells are of note. These cells are involved in the production of natural antibodies. In the present study, we determined whether manipulation of the intestinal microbiota by administration of probiotics, which we had previously shown to enhance specific systemic antibody response, could affect the development of natural antibodies in the intestines and sera of chickens. Our findings demonstrate that when 1-day-old chicks were treated with probiotics, serum and intestinal antibodies reactive to tetanus toxoid (TT) and Clostridium perfringens alpha-toxin in addition to intestinal immunoglobulin A (IgA) reactive to bovine serum albumin (BSA) were increased in unimmunized chickens. Moreover, IgG antibodies reactive to TT were increased in the intestines of probiotic-treated chickens compared to those of untreated controls. In serum, IgG and IgM reactive to TT and alpha-toxin were increased in probiotic-treated, unimmunized chickens compared to levels in untreated controls. However, no significant difference in serum levels of IgM or IgG response to BSA was observed. These results are suggestive of the induction of natural antibodies in probiotic-treated, unimmunized chickens. Elucidating the role of these antibodies in maintenance of the chicken immune system homeostasis and immune response to pathogens requires further investigation.

  7. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    Science.gov (United States)

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications.

  8. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    Directory of Open Access Journals (Sweden)

    Aikaterini Papazi

    Full Text Available Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939 and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications.

  9. Lichen Symbiosis: Nature's High Yielding Machines for Induced Hydrogen Production

    Science.gov (United States)

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont’s and photobiont’s consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont’s hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211

  10. Variations in mitochondrial membrane potential correlate with malic acid production by natural isolates of Saccharomyces cerevisiae sake strains.

    Science.gov (United States)

    Oba, Takahiro; Kusumoto, Kenichi; Kichise, Yuki; Izumoto, Eiji; Nakayama, Shunichi; Tashiro, Kosuke; Kuhara, Satoru; Kitagaki, Hiroshi

    2014-08-01

    Research on the relationship between mitochondrial membrane potential and fermentation profile is being intensely pursued because of the potential for developing advanced fermentation technologies. In the present study, we isolated naturally occurring strains of yeast from sake mash that produce high levels of malic acid and demonstrate that variations in mitochondrial membrane potential correlate with malic acid production. To define the underlying biochemical mechanism, we determined the activities of enzymes required for malic acid synthesis and found that pyruvate carboxylase and malate dehydrogenase activities in strains that produce high levels of malic acid were elevated compared with the standard sake strain K901. These results inspired us to hypothesize that decreased mitochondrial membrane potential was responsible for increased malic acid synthesis, and we present data supporting this hypothesis. Thus, the mitochondrial membrane potential of high malic acid producers was lower compared with standard strains. We conclude that mitochondrial membrane potential correlates with malic acid production.

  11. NATURAL ANTIOXIDANT INGREDIENT FROM BY-PRODUCTS OF FRUITS

    Directory of Open Access Journals (Sweden)

    G. S. El-Baroty

    2014-01-01

    used safely in the edible oil industry and cosmetics to delay its oxidation. It can be applied in other food industries as a natural antioxidant instead of synthetic antioxidants. Further study should be carried out to identify the predominant phenolics responsible for the antioxidant activity of by product extracts.

  12. Production of substitute natural gas by biomass hydrogasification

    Energy Technology Data Exchange (ETDEWEB)

    Mozaffarian, M.; Zwart, R.W.R. [ECN Biomass, Petten (Netherlands)

    2000-11-01

    Hydrogen, generated from renewable sources, is likely to play a major role in the future energy supply. The storage and transport of hydrogen can take place in its free form (H2), or chemically bound, e.g. as methane. However, the storage and transport of hydrogen in its free form are more complex, and probably would require more energy than the storage and transport of hydrogen in chemical form. An additional important advantage of the indirect use of hydrogen as energy carrier is, that in the future renewable energy supply, pads of the existing large-scale energy infra- structure could still be used. Production of Substitute Natural Gas (SNG) by biomass hydrogasification has been assessed as a process for chemical storage of hydrogen. Thermodynamic analysis has shown the feasibility of this process. The product gas of the process has a Wobbe-index, a mole percentage methane, and a calorific value quite comparable to the quality of the Dutch natural gas. With a hydrogen content below 10 mol%, the produced SNG can be transported through the existing gas net without any additional adjustment. The integrated system has an energetic efficiency of 81% (LHV). In the long term, the required hydrogen for this process can be produced by water electrolysis, with electricity from renewable sources. In the short term, hydrogen may be obtained from hydrogen-rich gases available as by-product from industrial processes. Results of thermodynamic analysis of the process and experimental work, application potentials of the process in the Netherlands, and plans for future development are presented. 21 refs.

  13. A General Approach to the Basiliolide/Transtaganolide Natural Products: Total Syntheses of Basiliolide B, epi-8-Basiliolide B, Transtaganolide C, and Transtaganolide D

    KAUST Repository

    Nelson, Hosea M.

    2011-03-25

    (Figure Presented) In a flash: The total synthesis of transtaganolide and basiliolide natural products is achieved in three steps from achiral, monocyclic esters (see scheme). Featured in the syntheses are an Ireland-Claisen/Diels- Alder cascade and a novel methoxyacetylide coupling/cyclization sequence. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA.

  14. Grubbs's Cross Metathesis of Eugenol with cis-2-butene-1, 4-diol to Make a Natural Product: An Organometallic Experiment for the Undergraduate Lab

    Science.gov (United States)

    Taber, Douglass F.; Frankowski, Kevin J.

    2006-01-01

    A modified experimental procedure for the one-step synthesis that is suitable for the undergraduate organic lab is presented. In the course of work towards the more routine use of air-sensitive organometallic complexes such as the Grubb's catalyst, the natural product (E)-4-(4-hydroxy-3-methoxyphenyl) but-2-en-ol, 4, was synthesized.

  15. Occurrence of aflatoxin B1 in natural products

    Directory of Open Access Journals (Sweden)

    Guilherme Prado

    2012-12-01

    Full Text Available The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15, immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg-1 and 1.0 µg kg-1respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 µg kg-1. The results revealed low aflatoxin B1contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination.

  16. Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin.

    Science.gov (United States)

    Irie, Kazuhiro; Yanagita, Ryo C

    2014-04-01

    Protein kinase C (PKC) isozymes play central roles in signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and teleocidins have the potential to become therapeutic leads, most of them are potent tumor promoters in mouse skin. By contrast, bryostatin-1 (bryo-1) isolated from marine bryozoan is a potent PKC activator with little tumor-promoting activity. Numerous investigations have suggested bryo-1 to be a promising therapeutic candidate for the above intractable diseases. However, there is a supply problem of bryo-1 both from natural sources and by organic synthesis. Recent approaches on the synthesis of bryo-1 have focused on its simplification, without decreasing the ability to activate PKC isozymes, to develop new medicinal leads. Another approach is to use the skeleton of natural PKC ligands to develop bryo-1 surrogates. We have recently identified 10-methyl-aplog-1 (26), a simplified analog of tumor-promoting aplysiatoxin (ATX), as a possible therapeutic lead for cancer. This review summarizes recent investigations on the simplification of natural PKC ligands, bryo-1 and ATX, to develop potential medicinal leads. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Ginkgo biloba: a natural reducing agent for the synthesis of cytocompatible graphene

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Park, Jung Hyun; Eppakayala, Vasuki; Kim, Jin-Hoi

    2014-01-01

    Background Graphene is a novel two-dimensional planar nanocomposite material consisting of rings of carbon atoms with a hexagonal lattice structure. Graphene exhibits unique physical, chemical, mechanical, electrical, elasticity, and cytocompatible properties that lead to many potential biomedical applications. Nevertheless, the water-insoluble property of graphene restricts its application in various aspects of biomedical fields. Therefore, the objective of this work was to find a novel biological approach for an efficient method to synthesize water-soluble and cytocompatible graphene using Ginkgo biloba extract (GbE) as a reducing and stabilizing agent. In addition, we investigated the biocompatibility effects of graphene in MDA-MB-231 human breast cancer cells. Materials and methods Synthesized graphene oxide (GO) and GbE-reduced GO (Gb-rGO) were characterized using various sequences of techniques: ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. Biocompatibility of GO and Gb-rGO was assessed in human breast cancer cells using a series of assays, including cell viability, apoptosis, and alkaline phosphatase (ALP) activity. Results The successful synthesis of graphene was confirmed by UV-vis spectroscopy and FTIR. DLS analysis was performed to determine the average size of GO and Gb-rGO. X-ray diffraction studies confirmed the crystalline nature of graphene. SEM was used to investigate the surface morphologies of GO and Gb-rGO. AFM was employed to investigate the morphologies of prepared graphene and the height profile of GO and Gb-rGO. The formation of defects in Gb-rGO was confirmed by Raman spectroscopy. The biocompatibility of the prepared GO and Gb-rGO was investigated using a water-soluble tetrazolium 8 assay on human breast cancer cells. GO exhibited a dose-dependent toxicity, whereas Gb

  18. Ginkgo biloba: a natural reducing agent for the synthesis of cytocompatible graphene.

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Park, Jung Hyun; Eppakayala, Vasuki; Kim, Jin-Hoi

    2014-01-01

    Graphene is a novel two-dimensional planar nanocomposite material consisting of rings of carbon atoms with a hexagonal lattice structure. Graphene exhibits unique physical, chemical, mechanical, electrical, elasticity, and cytocompatible properties that lead to many potential biomedical applications. Nevertheless, the water-insoluble property of graphene restricts its application in various aspects of biomedical fields. Therefore, the objective of this work was to find a novel biological approach for an efficient method to synthesize water-soluble and cytocompatible graphene using Ginkgo biloba extract (GbE) as a reducing and stabilizing agent. In addition, we investigated the biocompatibility effects of graphene in MDA-MB-231 human breast cancer cells. Synthesized graphene oxide (GO) and GbE-reduced GO (Gb-rGO) were characterized using various sequences of techniques: ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. Biocompatibility of GO and Gb-rGO was assessed in human breast cancer cells using a series of assays, including cell viability, apoptosis, and alkaline phosphatase (ALP) activity. The successful synthesis of graphene was confirmed by UV-vis spectroscopy and FTIR. DLS analysis was performed to determine the average size of GO and Gb-rGO. X-ray diffraction studies confirmed the crystalline nature of graphene. SEM was used to investigate the surface morphologies of GO and Gb-rGO. AFM was employed to investigate the morphologies of prepared graphene and the height profile of GO and Gb-rGO. The formation of defects in Gb-rGO was confirmed by Raman spectroscopy. The biocompatibility of the prepared GO and Gb-rGO was investigated using a water-soluble tetrazolium 8 assay on human breast cancer cells. GO exhibited a dose-dependent toxicity, whereas Gb-rGO-treated cells showed significant

  19. Natural gas productive capacity for the lower 48 states 1985 through 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    This publication presents information on wellhead productive capacity and a projection of gas production requirements. A history of natural gas production and productive capacity at the wellhead, along with a projection of the same, is illustrated.

  20. Coupling of glycerol processing with Fischer-Tropsch synthesis for production of liquid fuels

    DEFF Research Database (Denmark)

    Simonetti, D.A.; Rass-Hansen, Jeppe; Kunkes, E.L.

    2007-01-01

    % methanol, ethanol, and acetone, which can be separated from the water by distillation and used in the chemical industry or recycled for conversion to gaseous products. This integrated process has the potential to improve the economics of "green'' Fischer-Tropsch synthesis by reducing capital costs......Liquid alkanes can be produced directly from glycerol by an integrated process involving catalytic conversion to H-2/CO gas mixtures (synthesis gas) combined with Fischer-Tropsch synthesis. Synthesis gas can be produced at high rates and selectivities suitable for Fischer-Tropsch synthesis (H-2/CO......, acetone, and acetol. Fischer -Tropsch synthesis experiments at 548 K and 5 bar over a Ru-based catalyst reveal that water, ethanol, and acetone in the synthesis gas feed have only small effects, whereas acetol can participate in Fischer -Tropsch chain growth, forming pentanones, hexanones, and heptanones...