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Sample records for alkaloids total synthesis

  1. Total synthesis, biosynthesis and biological profiles of clavine alkaloids.

    Science.gov (United States)

    McCabe, Stephanie R; Wipf, Peter

    2016-07-01

    This review highlights noteworthy synthetic and biological aspects of the clavine subfamily of ergot alkaloids. Recent biosynthetic insights have laid the groundwork for a better understanding of the diverse biological pathways leading to these indole derivatives. Ergot alkaloids were among the first fungal-derived natural products identified, inspiring pharmaceutical applications in CNS disorders, migraine, infective diseases, and cancer. Pergolide, for example, is a semi-synthetic clavine alkaloid that has been used to treat Parkinson's disease. Synthetic activities have been particularly valuable to facilitate access to rare members of the Clavine family and empower medicinal chemistry research. Improved molecular target identification tools and a better understanding of signaling pathways can now be deployed to further extend the biological and medical utility of Clavine alkaloids. PMID:27215547

  2. The Total Synthesis of Galbulimima Alkaloid (+/-) G. B. 13 and the Development of an Anomalous Heck Reaction

    OpenAIRE

    Larson, Kimberly Katherine

    2009-01-01

    This dissertation describes our strategy for the total synthesis of Galbulimima alkaloid ()-G. B. 13. First, an overview of the isolation and structural classification of the twenty-eight alkaloids in the Galbulimima family is presented. Proposals for the biosyntheses of these natural products as well as the determination of their absolute stereochemical relationships are discussed. Additionally, the biological and medicinal properties of himbacine, another Galbulimima alkaloid, are present...

  3. Copper catalysed synthesis of indolylquinazolinone alkaloid bouchardatine

    Indian Academy of Sciences (India)

    Mayavan Viji; Rajagopal Nagarajan

    2014-07-01

    We describe the total synthesis of indolylquinazolinone alkaloid bouchardatine and some of the quinazolinone derivatives. The aerobic oxidation induced by copper(I) bromide, followed by Vilsmeier-Haack formylation gives the natural product bouchardatine alkaloid in good yield.

  4. First total synthesis of a guanidine alkaloid Nitensidine D using immobilized ionic liquid, microwaves and formamidinesulfinic acid

    Indian Academy of Sciences (India)

    Shallu; M L Sharma; Jasvinder Singh

    2014-11-01

    An efficient first total synthesis of a naturally occurring guanidine alkaloid, Nitensidine D isolated from ethanol extract of Pterogyne nitens has been described. Geraniol has been used as the starting material. N-alkylation of phthalimide has been achieved using immobilized ionic liquid and formamidinesulfinic acid acts as the guanylating reagent.

  5. Cytotoxic 1,3-Thiazole and 1,2,4-Thiadiazole Alkaloids from Penicillium oxalicum: Structural Elucidation and Total Synthesis

    Directory of Open Access Journals (Sweden)

    Zheng Yang

    2016-02-01

    Full Text Available Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3, were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473, one of important cancer drugs target.

  6. Synthesis of the isoquinoline alkaloid, crispine C

    OpenAIRE

    Blair, A.; Stevenson, L; Sutherland, A

    2012-01-01

    The first total synthesis of the isoquinoline alkaloid, crispine C is described in seven steps using a Henry reaction and the Pictet–Gams variant of the Bischler–Napieralski reaction to effect the key transformations.

  7. A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

    Science.gov (United States)

    Sherwood, Trevor C; Trotta, Adam H; Snyder, Scott A

    2014-07-01

    Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy for dimer formation that obviates these difficulties, one which rapidly constructs the coccinellid dimers psylloborine A and isopsylloborine A through a terminating sequence of two reaction cascades that generate five bonds, five rings, and four stereocenters. In addition, a common synthetic intermediate is identified which allows for the rapid, asymmetric formal or complete total syntheses of eight monomeric members of the class. PMID:24959981

  8. Total Synthesis of the Strychnos Alkaloid (+)-Minfiensine: Tandem Enantioselective Intramolecular Heck–Iminium Ion Cyclization

    OpenAIRE

    Dounay, Amy B.; Humphreys, Philip G.; Overman, Larry E.; Wrobleski, Aaron D.

    2008-01-01

    A 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (4) is a central structural feature of the Strychnos alkaloid minfiensine (1) and akuammiline alkaloids such as vincorine (5) and echitamine (6). A cascade catalytic asymmetric Heck-iminium cyclization was developed that rapidly provides 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazoles in high enantiomeric purity. Two sequences were developed for advancing 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole 27 to (+)-minfiensine. In our first-genera...

  9. A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

    OpenAIRE

    Sharpe, Robert J.; Johnson, Jeffrey S.

    2015-01-01

    A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C–H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.

  10. A Strategy for Complex Dimer Formation When Biomimicry Fails: Total Synthesis of Ten Coccinellid Alkaloids

    OpenAIRE

    Sherwood, Trevor C.; Trotta, Adam H.; Snyder, Scott A.

    2014-01-01

    Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature’s presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strat...

  11. An efficient synthesis of loline alkaloids

    Science.gov (United States)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

    Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

  12. Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids

    OpenAIRE

    Ewen D. D. Calder; McGonagle, Fiona I.; Harkiss, Alexander H.; McGonagle, Grant A.; Sutherland, Andrew

    2014-01-01

    Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramol...

  13. Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids.

    Science.gov (United States)

    Calder, Ewen D D; McGonagle, Fiona I; Harkiss, Alexander H; McGonagle, Grant A; Sutherland, Andrew

    2014-08-15

    Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann-Beller palladacycle was used to effect the key step during the synthesis of the natural products. PMID:25060853

  14. Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins

    Directory of Open Access Journals (Sweden)

    Yasufumi Wada

    2010-04-01

    Full Text Available Manynatural products with biologically interesting structures have been isolated from marine animals and plants such as sponges, corals, worms, etc. Some of them are discorhabdin alkaloids. The discorhabdin alkaloids (discorhabdin A-X, isolated from marine sponges, have a unique structure with azacarbocyclic spirocyclohexanone and pyrroloiminoquinone units. Due to their prominent potent antitumor activity, discorhabdins have attracted considerable attention. Many studies have been reported toward the synthesis of discorhabdins. We have accomplished the first total synthesis of discorhabdin A (1, having the strongest activity in vitro among discorhabdins in 2003. In 2009, we have also accomplished the first total synthesis of prianosin B (2, having the 16,17-dehydropyrroloiminoquinone moiety, by a novel dehydrogenation reaction with a catalytic amount of NaN3. These synthetic studies, as well as syntheses of the discorhabdins by various chemists to-date, are reviewed here.

  15. Total synthesis of atropurpuran.

    Science.gov (United States)

    Gong, Jing; Chen, Huan; Liu, Xiao-Yu; Wang, Zhi-Xiu; Nie, Wei; Qin, Yong

    2016-01-01

    Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.0(4,9).0(4,12)]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (±)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. PMID:27387707

  16. Total Synthesis of Millingtonine.

    Science.gov (United States)

    Brown, Patrick D; Lawrence, Andrew L

    2016-07-11

    Millingtonine is a glycosidic alkaloid that exists as a pair of pseudo-enantiomeric diastereomers. Consideration of the likely biosynthetic origins of this unusual natural product has resulted in the development of a seven-step total synthesis. Results from this synthetic work provide evidence in support of a proposed network of biosynthetic pathways that can account for the formation of several phenylethanoid natural products. PMID:27249628

  17. Enantioselective Total Synthesis of (+)-Gliocladin C

    OpenAIRE

    Overman, Larry E.; Shin, Youseung

    2007-01-01

    The first total synthesis of gliocladin C, a fungal-derived marine alkaloid containing a rare trioxopiperazine fragment, is reported. This asymmetric synthesis establishes the absolute configuration of this structurally novel natural product.

  18. Total Synthesis of (-)-Daphenylline.

    Science.gov (United States)

    Yamada, Ryosuke; Adachi, Yohei; Yokoshima, Satoshi; Fukuyama, Tohru

    2016-05-10

    Total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid, was achieved. Construction of the tricyclic DEF ring system was initiated by asymmetric Negishi coupling followed by an intramolecular Friedel-Crafts reaction. Installation of a side chain onto the tricyclic core was carried out through Sonogashira coupling, stereocontrolled Claisen rearrangement by taking advantage of the characteristic conformation of the tricyclic DEF core, and the stereoselective alkylation of a lactone. After the introduction of a glycine unit, the ABC ring system was stereoselectively constructed through intramolecular cycloaddition of the cyclic azomethine ylide. PMID:27062676

  19. Total synthesis of (±)-isophellibiline

    OpenAIRE

    Funk, Raymond L.; Belmar, Johannes

    2012-01-01

    The total synthesis of (±)-isophellibiline is described. This represents the first synthesis of a member of the nonaromatic homoerythrinan family of alkaloids. The tetracyclic ring system of the natural product was quickly assembled by a strategy that features a retrocycloaddition/cycloaddition reaction of an amidodioxin, an intramolecular Heck reaction and a 6π-electrocyclic ring closure of a dienoic acid.

  20. An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Linfeng Li

    2014-09-01

    Full Text Available Recently, we characterized neoamphimedine (neo as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%. In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM. We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis.

  1. Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

    OpenAIRE

    Kieron M. G. O’Connell; Monica Díaz-Gavilán; Galloway, Warren R. J. D.; Spring, David R.

    2012-01-01

    Two-directional synthesis represents an ideal strategy for the rapid elaboration of simple starting materials and their subsequent transformation into complex molecular architectures. As such, it is becoming recognised as an enabling technology for diversity-oriented synthesis. Herein, we provide a thorough account of our work combining two-directional synthesis with diversity-oriented synthesis, with particular reference to the synthesis of polycyclic alkaloid scaffolds.

  2. Total Synthesis of (-)-Cardiopetaline.

    Science.gov (United States)

    Nishiyama, Yoshitake; Yokoshima, Satoshi; Fukuyama, Tohru

    2016-05-20

    The total synthesis of (-)-cardiopetaline, an aconitine-type natural product, has been accomplished. Our synthesis involved a Wagner-Meerwein rearrangement of a sulfonyloxirane that enabled, in a single step, the construction of the bicyclo[3.2.1] system in the aconitine skeleton and effective introduction of oxygen functional groups at the appropriate positions. PMID:27166640

  3. Unified Synthesis of 10-Oxygenated Lycopodium Alkaloids: Impact of C10-Stereochemistry on Reactivity.

    Science.gov (United States)

    Saha, Mrinmoy; Li, Xin; Collett, Nathan D; Carter, Rich G

    2016-07-15

    The pronounced impact of the C10 stereochemistry on the successful construction of a polycyclic Lycopodium alkaloid scaffold has been explored. A wide range of reaction conditions and functionality were investigated to control a keto sulfone Michael addition to construct the C7-C12 linkage. An unexpected, overriding impact of the C10 stereochemistry in stereoselectivity and reaction rate in the Michael addition was observed. Furthermore, divergent reactivity of a conformationally accelerated, intramolecular Mannich cyclization based on the C10 stereochemistry was discovered. The successful execution of this synthetic route resulted in the total synthesis of all three known 10-oxygenated Lycopodium alkaloids: 10-hydroxylycopodine, paniculine, and deacetylpaniculine. PMID:27353498

  4. Synthesis studies on the Melodinus alkaloid meloscine

    OpenAIRE

    Feldman, Ken S.; Antoline, Joshua F.

    2013-01-01

    The pentacyclic Melodinus alkaloid (±)-meloscine was synthesized in 19 chemical steps from 2-bromobenzaldehyde through a route featuring an allenyl azide cyclization cascade to deliver the core azabicyclo[3.3.0]octane substructure. Peripheral functionalization of this core included a Tollens-type aldol condensation to set the quaternary center at C(20) and a diastereoselective ring closing metathesis to forge the tetrahydropyridine ring.

  5. Total Synthesis of Teixobactin.

    Science.gov (United States)

    Giltrap, Andrew M; Dowman, Luke J; Nagalingam, Gayathri; Ochoa, Jessica L; Linington, Roger G; Britton, Warwick J; Payne, Richard J

    2016-06-01

    The first total synthesis of the cyclic depsipeptide natural product teixobactin is described. Synthesis was achieved by solid-phase peptide synthesis, incorporating the unusual l-allo-enduracididine as a suitably protected synthetic cassette and employing a key on-resin esterification and solution-phase macrolactamization. The synthetic natural product was shown to possess potent antibacterial activity against a range of Gram-positive pathogenic bacteria, including a virulent strain of Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA). PMID:27191730

  6. Total synthesis of teixobactin.

    Science.gov (United States)

    Jin, Kang; Sam, Iek Hou; Po, Kathy Hiu Laam; Lin, Du'an; Ghazvini Zadeh, Ebrahim H; Chen, Sheng; Yuan, Yu; Li, Xuechen

    2016-01-01

    To cope with the global bacterial multidrug resistance, scientific communities have devoted significant efforts to develop novel antibiotics, particularly those with new modes of actions. Teixobactin, recently isolated from uncultured bacteria, is considered as a promising first-in-class drug candidate for clinical development. Herein, we report its total synthesis by a highly convergent Ser ligation approach and this strategy allows us to prepare several analogues of the natural product. PMID:27484680

  7. Total synthesis of ochnaflavone

    OpenAIRE

    Monica M. Ndoile; van Heerden, Fanie R

    2013-01-01

    The first total syntheses of ochnaflavone, an asymmetric biflavone consisting of apigenin and luteolin moieties, and the permethyl ether of 2,3,2'',3''-tetrahydroochnaflavone have been achieved. The key steps in the synthesis of ochnaflavone were the formation of a diaryl ether and ring cyclization of an ether-linked dimeric chalcone to assemble the two flavone nuclei. Optimal experimental conditions for the oxidative cyclization to form ochnaflavone were established.

  8. Total synthesis of ochnaflavone

    Directory of Open Access Journals (Sweden)

    Monica M. Ndoile

    2013-07-01

    Full Text Available The first total syntheses of ochnaflavone, an asymmetric biflavone consisting of apigenin and luteolin moieties, and the permethyl ether of 2,3,2'',3''-tetrahydroochnaflavone have been achieved. The key steps in the synthesis of ochnaflavone were the formation of a diaryl ether and ring cyclization of an ether-linked dimeric chalcone to assemble the two flavone nuclei. Optimal experimental conditions for the oxidative cyclization to form ochnaflavone were established.

  9. Total synthesis of (-)-spinosyn A.

    Science.gov (United States)

    Mergott, Dustin J; Frank, Scott A; Roush, William R

    2004-08-17

    A convergent, highly stereoselective total synthesis of (-)-spinosyn A (1) is described. Key features of the synthesis include the transannular Diels-Alder reaction of macrocyclic pentaene 11 and the transannular Morita-Baylis-Hillman cyclization of 12 that generates tetracycle 26. The total synthesis of (-)-spinosyn A was completed by a sequence involving the highly beta-selective glycosidation reaction of 13 and glycosyl imidate 30. PMID:15173590

  10. Studies on quantitative determination of total alkaloids and berberine in five origins of crude medicine "Sankezhen".

    Science.gov (United States)

    Li, Luyang; Long, Weifang; Wan, Xiangluan; Ding, Qi; Zhang, Fei; Wan, Dingrong

    2015-02-01

    The roots of Berberis plants are widely used as a traditional Chinese medicine called "Sankezhen", having the activities of antibacterial and anti-inflammatory, and the ingredients are alkaloids. This work aims to study and compare the total alkaloids and individual alkaloid (berberine) contents in roots and stems from five origins of Berberis plants (Berberis soulieana Schneid., B. henryana Schneid., B. triacanthophora Fedde, B. gagnepainii Schneid. and B. bergmanniae Schneid.) and provides some references for resource and quality evaluation of the medicine. Acid dye colorimetry and high-performance liquid chromatography were used in the determination. The results showed that the contents for the total alkaloids in root and stem samples were in the range of 1.60-4.72% and 0.76-2.70%, while those of the berberine were 0.70-2.92% and 0.23-1.07%. With higher contents of the total alkaloids and berberine, the roots of B. soulieana, B. gagnepainii and B. bergmanniae were good sources of "Sankezhen". Meanwhile, the contents were also high in stems of the three plants, indicating that the stems were likely to be alternative sources of "Sankezhen" after further research. As the results of precision, stability and recovery tests shown, the methods were simple, rapid and reliable, and provided valuable basis for quality evaluation and new resource investigation of "Sankezhen". PMID:25013028

  11. Synthesis of 1-Substituted Isoquinolines by Heterocyclization of TosMIC Derivatives: Total Synthesis of Cassiarin A.

    Science.gov (United States)

    Gutiérrez, Sara; Coppola, Anna; Sucunza, David; Burgos, Carolina; Vaquero, Juan J

    2016-07-15

    A new method for the synthesis of 1-substituted isoquinolines by a heterocyclization that involves α-benzyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to a total synthesis of cassiarin A, an alkaloid with potent antiplasmodial activity against Plasmodium falciparum. PMID:27351205

  12. Total Synthesis of Propolisbenzofuran B†

    OpenAIRE

    Jones, Brian T.; Avetta, Christopher T.; Thomson, Regan J.

    2014-01-01

    The first total synthesis of propolisbenzofuran B, a bioactive natural product isolated from honeybee propolis resin, is reported. The convergent synthesis makes use of a silicon-tether controlled oxidative ketone–ketone cross-coupling and a novel benzofuran-generating cascade reaction to deliver the core structure of the natural product from readily prepared precursors.

  13. Total Synthesis of Kealiinines A-C, Kealiiquinone, 2-Deoxy-2-aminokealiiquinone and Study Towards Total Synthesis of Spirocalcaridines A-B

    Science.gov (United States)

    Das, Jayanta Kumar

    Our group is mainly interested in the total synthesis of imidazole-containing alkaloids along with other kinds of alkaloids. A new family of imidazole alkaloids, the Leucetta alkaloids, is a group of 60 or so 2-aminoimidazole natural products found in marine sponges, which have received substantial attention recently because of their challenging structures and strong biological activities. Over the past few years, our laboratory has developed several synthetic methods for the total synthesis of 2-aminoimidazole alkaloids using site selective functionalization of polyhaloimidazoles. By using the above synthetic strategy, the development of high yielding and protecting group-free total syntheses of the reported structures of the Leucetta alkaloids kealiinine A-C has been accomplished. In addition to the challenging syntheses of these, our data unequivocally prove that the reported structures of those natural products did not match synthetic material due to discrepancies in the interpretation of spectroscopic data during initial isolation and characterization. Finally, the correct structure assignment was achieved with the help of extensive experimentation using 2D NMR spectroscopy (HMBC, HSQC and ROESY) and X-ray crystallography of these synthetic natural products. A second set of targets was accessed using a biosynthetic guided strategy according to which, kealiinine C would serve as a precursor to kealiiquinone and 2-deoxy-2-aminokealiiquinone. The synthesis of both alkaloids was completed from a late stage intermediate from the kealiinine C synthesis by oxidation. Although the first total synthesis of kealiiquinone was accomplished by Ohta et al. in 1995, the current method was protecting group-free and required only 6 steps in comparison to 12 steps by the Japanese group. The first total synthesis of the 2-amino congener was also accomplished. After successful syntheses of those natural products, in collaboration with Dr. Mandal's group, the cytotoxicity of these

  14. Concise total synthesis and structural revision of (+)-pestalazine B.

    Science.gov (United States)

    Pérez-Balado, Carlos; de Lera, Angel R

    2010-11-21

    A convergent synthesis of the proposed structure of (+)-pestalazine B has been achieved in 4 steps using the N-alkylation of an unprotected tryptophan diketopiperazine with a 3a-bromopyrrolidinoindoline as the key step. Although its structure was confirmed by X-ray analysis, the spectroscopic data did not match those of the natural product. The versatility of the methodology allowed the preparation of several diastereomers, and the database generated led to the proposal of an isomeric structure for the natural alkaloid where the d-leucine and d-phenylalanine residues exchanged positions, which was corroborated by total synthesis. PMID:20848034

  15. Diastereoselective Total Synthesis of (-)-Galiellalactone.

    Science.gov (United States)

    Kim, Taewoo; Han, Young Taek; An, Hongchan; Kim, Kyeojin; Lee, Jeeyeon; Suh, Young-Ger

    2015-12-18

    An enantioselective total synthesis of (-)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the cis-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (-)-galiellalactone via a combination of diastereoselective Hosomi-Sakurai crotylation and ring-closing metathesis (RCM). PMID:26544529

  16. First total synthesis of Boehmenan

    Indian Academy of Sciences (India)

    Yamu Xia; Xiaoli Dai; Haixin Liu; Chen Chai

    2014-05-01

    The first total synthesis of dilignan Boehmenan has been achieved. A biomimetic oxidative coupling of the ferulic acid methyl ester in the presence of silver oxide is the crucial step in the synthesis sequence, generating the dihydrobenzofuran skeleton. Hydroxyl group was protected with DHP and reducted with LiAlH4 to afford the intermediate diol. The diol was condensated with the derivative of ferulic acid, then removed the protecting groups, to get Boehmenan. Meanwhile, a study on the ring-opening reaction of the intermediate dihydrobenzofuran neolignan under base conditions was described.

  17. Simple Indolizidine and Quinolizidine Alkaloids.

    Science.gov (United States)

    Michael, Joseph P

    2016-01-01

    This review of simple indolizidine and quinolizidine alkaloids (i.e., those in which the parent bicyclic systems are in general not embedded in polycyclic arrays) is an update of the previous coverage in Volume 55 of this series (2001). The present survey covers the literature from mid-1999 to the end of 2013; and in addition to aspects of the isolation, characterization, and biological activity of the alkaloids, much emphasis is placed on their total synthesis. A brief introduction to the topic is followed by an overview of relevant alkaloids from fungal and microbial sources, among them slaframine, cyclizidine, Steptomyces metabolites, and the pantocins. The important iminosugar alkaloids lentiginosine, steviamine, swainsonine, castanospermine, and related hydroxyindolizidines are dealt with in the subsequent section. The fourth and fifth sections cover metabolites from terrestrial plants. Pertinent plant alkaloids bearing alkyl, functionalized alkyl or alkenyl substituents include dendroprimine, anibamine, simple alkaloids belonging to the genera Prosopis, Elaeocarpus, Lycopodium, and Poranthera, and bicyclic alkaloids of the lupin family. Plant alkaloids bearing aryl or heteroaryl substituents include ipalbidine and analogs, secophenanthroindolizidine and secophenanthroquinolizidine alkaloids (among them septicine, julandine, and analogs), ficuseptine, lasubines, and other simple quinolizidines of the Lythraceae, the simple furyl-substituted Nuphar alkaloids, and a mixed quinolizidine-quinazoline alkaloid. The penultimate section of the review deals with the sizable group of simple indolizidine and quinolizidine alkaloids isolated from, or detected in, ants, mites, and terrestrial amphibians, and includes an overview of the "dietary hypothesis" for the origin of the amphibian metabolites. The final section surveys relevant alkaloids from marine sources, and includes clathryimines and analogs, stellettamides, the clavepictines and pictamine, and bis

  18. Pharmacological Evaluation of Total Alkaloids from Nux Vomica: Effect of Reducing Strychnine Contents

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2014-04-01

    Full Text Available The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF. The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP. In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

  19. Stereoselective Total Synthesis of Mycalamides

    Institute of Scientific and Technical Information of China (English)

    Masahiro Toyota

    2005-01-01

    @@ 1Introduction Mycalamides A (1a) and B (1b) are potent antiviral compounds from a New Zealand sponge of the genus Mycale. Apart from their antitumor property, mycalamide A (1a) exhibits immunosuppressive action by blocking T-cell activation in mice and is significantly more potent than FK-506 and cyclosporine A. Because of their intriguing biological activity, unique structures and scarce supply of these natural products, mycalamides A (1a) and B (1b) have attracted considerable attention as target molecules for total synthesis, and total, formal, or partial syntheses of this family of compounds have been reported[1,2].

  20. A Concise Total Synthesis of S-(+)-Tylophorine

    Institute of Scientific and Technical Information of China (English)

    JIN,Zhong; WANG,Qing-Min; LI,Hao; LIU,Yu-Xiu; LI,Shi-Pu; HUANG,Run-Qiu

    2004-01-01

    @@ Phenanthroindolizidine alkaloids, which exhibit extensively biological properties, are widely present at various plants of the Asclepiadaceae family.[1] The significantly biological importance of these natural products has attracted considerable synthetic efforts.[2] We herein report an efficiently asyinmetric synthesis of S-(+)-tylophorine (1), as a typically representative alkaloids.

  1. Cu-Mediated Stille Reactions of Sterically Congested Fragments: Towards the Total Synthesis of Zoanthamine

    DEFF Research Database (Denmark)

    Nielsen, Thomas E.; Le Quement, Sebastian; Juhl, Martin; Tanner, David Ackland

    2005-01-01

    A study on the Stille reaction of alkenyl iodides and starmanes with structural resemblance to retrosynthetic fragments of a projected total synthesis of the marine alkaloid zoanthamine was carried out. A range of reaction conditions was examined, and a protocol developed by Corey utilizing excess...

  2. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

    OpenAIRE

    Alessandra Mirtes Marques Neves Gonçalves; Aline Brito de Lima; Maria Cristina da Silva Barbosa; Luiz Fernando de Camargos; Júlia Teixeira Oliveira; Camila de Souza Barbosa; José Augusto Ferreira Perez Villar; André Carvalho Costa; Isabella Viana Gomes da Silva; Luciana Maria Silva; Fernando de Pilla Varotti; Fabio Vieira dos Santos; Gustavo Henrique Ribeiro Viana

    2014-01-01

    Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a ...

  3. Isolation, structure elucidation, and biomimetic total synthesis of versicolamide B and the isolation of antipodal (-)-stephacidin A and (+)-notoamide B from Aspergillus versicolor

    Science.gov (United States)

    A new prenylated indole alkaloid, versicolamide B, was isolated from cultures of Aspergillus versicolor NRRL 35600. The structure was assigned by 2D NMR data, and confirmed by a biomimetic total synthesis. Versicolamide B is the first member of the paraherquamide-stephacidin family of alkaloids fo...

  4. Total Synthesis of the Ammosamides

    Science.gov (United States)

    Hughes, Chambers C.; Fenical, William

    2010-01-01

    The ammosamides A-C are chlorinated pyrrolo[4,3,2-de]quinoline metabolites isolated from the marine-derived Streptomyces strain CNR-698. The natural products, which possess a dense array of heteroatoms, were synthesized in 17–19 steps from 4-chloroisatin. That the five nitrogen atoms were introduced at the appropriate time and in a suitable oxidation state was key to the success of the total synthesis. Compared to synthetic deschloro ammosamide B, natural ammosamide B is much less susceptible to oxidative degradation. PMID:20131899

  5. Synthesis of bicyclic alkaloids from the iridoid antirrhinoside

    DEFF Research Database (Denmark)

    Frederiksen, Signe Maria

    The present thesis describes the isolation of the iridoid glucoside antirrhinoside from Antirrhinum majus, and the approaches made towards its transformation into analogues of biologically active compounds, with special interest in syntheses of bicyclic alkaloids.A synthetic piperidine monoterpene...... alkaloids. The corresponding ditosyl derivative was treated with benzylamine to afford a bicyclic N-benzylated pyrrolidine. An alternative starting material was prepared from 5,6:4',6'-di-O-isopropylidene antirrhinoside by reduction with lithium aluminum hydride. Subsequent ozonolysis and sodium borohydride...... gave the expected triol. The corresponding ditosyl derivative was treated with benzylamine or 2-methoxy-benzylamine to afford bicyclic pyrrolidines in 54-66% yield. The isopropylidene protection was removed and the unprotected pyrrolidine was acylated with benzoyl chloride to afford a potential...

  6. Modular Total Synthesis of Protein Kinase C Activator (-)-Indolactam V.

    Science.gov (United States)

    Haynes-Smith, Jeremy; Diaz, Italia; Billingsley, Kelvin L

    2016-05-01

    A concise, eight-step total synthesis of (-)-indolactam V, a nanomolar agonist of protein kinase C, is reported. The synthesis relies upon an efficient copper-catalyzed amino acid arylation to establish the indole C4-nitrogen bond. This cross-coupling method is applicable to a range of hydrophobic amino acids, providing a platform for further diversification of indolactam alkaloid scaffolds and studies on their potent biological activity. PMID:27074538

  7. Screening for total ergot alkaloids in rye flour by planar solid phase extraction-fluorescence detection and mass spectrometry.

    Science.gov (United States)

    Oellig, Claudia; Melde, Tina

    2016-04-01

    The analysis of ergot alkaloids is generally performed by high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FLD) or mass selective detection. As for monitoring only the sum of ergot alkaloids is relevant, a fast and easy screening method for the determination of the total alkaloid content was developed using planar solid phase extraction (pSPE). Applying pSPE, recently introduced for pesticide residue analysis in fruits and vegetables (Oellig and Schwack, 2011) and tea (Oellig and Schwack, 2012), all ergot alkaloids are concentrated in a target zone followed by detection as the sum. The herein presented method includes an ammonium acetate buffered extraction step, followed by a fast liquid-liquid partitioning pre-cleaning before pSPE is performed on high-performance thin-layer chromatography (HPTLC) amino plates with a single methanol development to separate the ergot alkaloids from the remaining matrix and to collect them in a single zone. For quantitation, the native fluorescence was used after dipping the plate in n-hexane/paraffin solution for fluorescence enhancement. Limits of detection and quantitation of 0.07 and 0.24mg/kg rye, respectively, expressed as ergocristine, were well below the currently applied quality criterion limit for rye. Near-100% recoveries were obtained at relevant spiking levels for different rye flour samples. Hence, the fast pSPE-FLD is an efficient and reliable method to screen for the total ergot alkaloid content in rye and a rapid alternative to the HPLC determination of individual alkaloids and to summing them up. HPTLC-MS additionally enables the identification of the ergot alkaloid composition by a single mass spectrum, when utilized as a fingerprint, offering an easy differentiation of Secale cornutum from different origins. PMID:26947163

  8. Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

    Directory of Open Access Journals (Sweden)

    Louis P. Sandjo

    2015-09-01

    Full Text Available This review focuses on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone, dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues, which are synthesized for biological purposes are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity.

  9. Synthesis of some 11C-labelled alkaloids

    International Nuclear Information System (INIS)

    Using (11C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-(11C-methyl)-morphine, N-(11C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-(11C-methyl)-bromocriptine and N-(11C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing (11C)-methyl iodide into the reaction vial. (11C)-Methyl iodide was obtained within 4-7 min from (11C)-carbon dioxide prepared by the 14N(p,α)11C reaction. (Authors)

  10. Concise Enantiospecific Total Synthesis of Tubingensin A

    OpenAIRE

    Goetz, Adam E.; Silberstein, Amanda L.; Corsello, Michael A.; Garg, Neil K.

    2014-01-01

    We report the enantiospecific total synthesis of (+)-tubingensin A. Our synthesis features an aryne cyclization to efficiently introduce the vicinal quaternary stereocenters of the natural product and proceeds in only nine steps (longest linear sequence) from known compounds.

  11. Total Synthesis and the Biological Activities of (±-Norannuradhapurine

    Directory of Open Access Journals (Sweden)

    Surachai Nimgirawath

    2008-12-01

    Full Text Available The structure previously assigned to the phenolic noraporphine alkaloid, (--norannuradhapurine has been confirmed by a total synthesis of the racemic alkaloid in which the key step involved the formation of the C ring by a radical-initiated cyclization. although inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028, (±-norannuradhapurine inhibits the production of NO, PGE2, TNF-a, IL-1b and IL-6 and the expression of iNOS and COX-2 in RAW 264.7 macrophages stimulated with LPS in vitro.

  12. Synthesis of some /sup 11/C-labelled alkaloids

    Energy Technology Data Exchange (ETDEWEB)

    Laangstroem, B.; Antoni, G.; Halldin, H.; Svaerd, H.; Bergson, G. (Univ. of Uppsala (Sweden) Inst. of Chemistry)

    1982-01-01

    Using (/sup 11/C)-methyl iodide in N-alkylation reactions in dimethylformamide (DMF), the alkaloids N-(/sup 11/C-methyl)-morphine, N-(/sup 11/C-methyl)-codeine, 6-N(methyl)-9, 10-dihydroergotamine, 6-N-(/sup 11/C-methyl)-bromocriptine and N-(/sup 11/C-methyl)-nicotine have been synthesized in radiochemical yields of 50-95%, within 5-10 min of introducing (/sup 11/C)-methyl iodide into the reaction vial. (/sup 11/C)-Methyl iodide was obtained within 4-7 min from (/sup 11/C)-carbon dioxide prepared by the /sup 14/N(p,..cap alpha..)/sup 11/C reaction.

  13. Patterns of indole alkaloids synthesis in response to heat shock, 5-azacytidine and Na-butyrate treatment of cultured catharanthus roseus mesophyll protoplasts

    International Nuclear Information System (INIS)

    Alkaloids of C. roseus are in high demand for therapeutic and other reasons. Cultured Catharanthus cells can produce limited quantities of these alkaloids. The authors have found that cultured mesophyll protoplasts in the presence of 14C-Tryptamine are capable of synthesizing alkaloids. The pattern of alkaloids synthesis changes when protoplasts are subjected to a heat shock at 370C. The heat shocked protoplasts incorporated 33% more 14C-Tryptamine and produced 3 new types of alkaloids. Treatment of protoplasts with 5-azacytidine, a DNA hypomethylating agent and Na-butyrate which induces hyperacetylation of histones produced qualitative and quantitative changes in the alkaloid pattern. Four new alkaloids following the above treatments were detected by TLC and HPLC of the extracts. It is suggested that the alkaloid pattern of the cultured protoplasts can be altered by treatment with compounds known as regulators of gene expression. Work is in progress to isolate and identify these new alkaloids

  14. Patterns of indole alkaloids synthesis in response to heat shock, 5-azacytidine and Na-butyrate treatment of cultured catharanthus roseus mesophyll protoplasts

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, M.; Cutler, A.J.

    1986-04-01

    Alkaloids of C. roseus are in high demand for therapeutic and other reasons. Cultured Catharanthus cells can produce limited quantities of these alkaloids. The authors have found that cultured mesophyll protoplasts in the presence of /sup 14/C-Tryptamine are capable of synthesizing alkaloids. The pattern of alkaloids synthesis changes when protoplasts are subjected to a heat shock at 37/sup 0/C. The heat shocked protoplasts incorporated 33% more /sup 14/C-Tryptamine and produced 3 new types of alkaloids. Treatment of protoplasts with 5-azacytidine, a DNA hypomethylating agent and Na-butyrate which induces hyperacetylation of histones produced qualitative and quantitative changes in the alkaloid pattern. Four new alkaloids following the above treatments were detected by TLC and HPLC of the extracts. It is suggested that the alkaloid pattern of the cultured protoplasts can be altered by treatment with compounds known as regulators of gene expression. Work is in progress to isolate and identify these new alkaloids.

  15. Biodegradable poly(lactic acid) microspheres containing total alkaloids of Caulis sinomenii

    Indian Academy of Sciences (India)

    Wen Zhang; Xiaojie Lin; Xingxiang Zhang

    2011-12-01

    The fabrication of biodegradable poly(lactic acid) (PLA) microspheres containing total alkaloids of Caulis sinomenii was investigated. The formation, diameter, morphology and properties of the microspheres were characterized using Fourier transform infrared spectroscopy (FT–IR), laser particle size analyser and scanning electron microscopy (SEM), etc. In vitro releasing behaviour was also investigated using UV-Vis spectrometer. As a result, the drug-loaded microspheres with a narrower distributive, rounder and smoother surface were prepared. Drug-releasing behaviour from microspheres was affected by the concentration of emulsifier and the stirring rate. The results demonstrated that a medicated system, which can be potentially applied within a drug delivery system, was designed. This system acts in a systematic manner for the treatment of rheumatoid arthritis.

  16. Effects of corydalis amabilis Migo total alkaloids on platelet cyclic AMP and cyclic GMP

    International Nuclear Information System (INIS)

    Corydalis amabilis Migo total alkaloids (COAMTA), isolated from the root of Corydalis decumbens (Thunb) Pers, possessed inhibitory action on ADP-induced blood platelet aggregation and the formation of thrombus in animal experiments. Its effects on the platelet cyclic AMP and cyclic GMP in incubated rabbit platelet were measured by radioimmunoassay. cAMP was significantly elevated when COAMTA was given 0.08-0.16 mg/ml PRP. In concentration up to 0.16 mg/ml PRP, COAMTA elevated cGMP, but the ratio value of cAMP/cGMP was much higher than that of control group. These results suggest that the anti-platelet activity of COAMTA were mediated through elevation of cAMP levels

  17. Double reductive cyclization: A facile synthesis of the indoloquinoline alkaloid cryptotackieine

    Digital Repository Service at National Institute of Oceanography (India)

    Parvatkar, P.T.; Parameswaran, P.S.; Tilve, S.G.

    University, Received 22 June 2007; revised 21 Available online Abstract—A new synthesis of the indoloquinoline alkaloid cryptotackieine, which involves a Perkin reaction, a tandem double reduction–double at the quinoline nitrogen. C211 2007 Elsevier Ltd. All...-4039/$ - see front matter C211 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2007.08.126 a facile synthesis cryptotackieine an a, * and S. G. Tilve b, * Dona Paula, Goa 403 207, India Taleigao Plateau, Goa 403 206, India 2007; accepted 30 August...

  18. Total synthesis of solanoeclepin A

    Science.gov (United States)

    Tanino, Keiji; Takahashi, Motomasa; Tomata, Yoshihide; Tokura, Hiroshi; Uehara, Taketo; Narabu, Takashi; Miyashita, Masaaki

    2011-06-01

    Cyst nematodes are troublesome parasites that live on, and destroy, a range of important host vegetable plants. Damage caused by the potato cyst nematode has now been reported in over 50 countries. One approach to eliminating the problem is to stimulate early hatching of the nematodes, but key hatching stimuli are not naturally available in sufficient quantities to do so. Here, we report the first chemical synthesis of solanoeclepin A, the key hatch-stimulating substance for potato cyst nematode. The crucial steps in our synthesis are an intramolecular cyclization reaction for construction of the highly strained tricyclo[5.2.1.01,6]decane skeleton (DEF ring system) and an intramolecular Diels-Alder reaction of a furan derivative for the synthesis of the ABC carbon framework. The present synthesis has the potential to contribute to addressing one of the critical food issues of the twenty-first century.

  19. Synthesis of Carbazole Alkaloids by Ring-Closing Metathesis and Ring Rearrangement-Aromatization.

    Science.gov (United States)

    Dhara, Kalyan; Mandal, Tirtha; Das, Joydeb; Dash, Jyotirmayee

    2015-12-21

    Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring-closing metathesis (RCM) and ringrearrangement-aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2-diallyl 3-oxindole derivatives through a 1,2-allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel class of spirocyclopentene-3-oxindole derivatives, which underwent a novel RRA reaction to afford carbazole derivatives. The synthetic sequence to carbazoles was shortened by combining the RCM and RRA steps in an orthogonal tandem catalytic process. The utility of this methodology was further demonstrated by the straightforward synthesis of carbazole alkaloids, including amukonal derivative, girinimbilol, heptaphylline, and bis(2-hydroxy-3-methylcarbazole). PMID:26768698

  20. A Convergent Enantioselective Total Synthesis of (-)-Perhydrohistrionicotoxin with an Intramolecular Imino Ene-type Reaction as a Key Step

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Hagberg, Lars

    1998-01-01

    A convergent enantioselective total synthesis of the neurotoxic spirocyclic alkaloid (-)-perhydrohistrionicotoxin (2) is described. A Lewis acid-mediated intramolecular imine ene-type reaction was used for the key spirocyclisation step (14 to 3, with 3 being obtained as a single diastereoisomer...

  1. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

    OpenAIRE

    Alois Plodek; Franz Bracher

    2016-01-01

    Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids...

  2. Total Synthesis of (-)-Luminacin D.

    Science.gov (United States)

    Malassis, Julien; Bartlett, Nathan; Hands, Kane; Selby, Matthew D; Linclau, Bruno

    2016-05-01

    A second-generation synthesis of (-)-luminacin D based on an early stage introduction of the trisubstituted epoxide group is reported, allowing access to the natural product in an improved yield and a reduced number of steps (5.4%, 17 steps vs 2.6%, 19 steps). A full account of the optimization work is provided, with the reversal of stereoselection in the formation of the C4 alcohol in equally excellent diastereoselectivity as the key improvement. PMID:27054953

  3. The total synthesis of (–)-crispatene

    OpenAIRE

    Miller, Aubry K.; Byun, Daniel H.; Beaudry, Christopher M.; Trauner, Dirk

    2004-01-01

    The total synthesis of the molluscan polypropionate (–)-crispatene is described. The synthesis features a palladium-catalyzed cross-coupling to establish a sensitive conjugated tetraene and its Lewis acid-catalyzed cycloisomerization to yield the bicyclo[3.1.0]hexene core of the natural product. The absolute configuration of (–)-crispatene and related molecules is established.

  4. A modified total synthesis of cystothiazole A

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    A modified total synthesis of cystothiazole A is described. In this synthetic strategy, a one-step transformation of acylated oxazolidinone to β-ketoester has been successfully applied, thus making the synthetic route more efficient. This method may also be potentially applied in synthesis of other related β-substituted-β-methoxyl acrylates (bb-MOAs).

  5. Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata

    Directory of Open Access Journals (Sweden)

    Noureddine Bribi

    2015-01-01

    Full Text Available Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2 in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis.

  6. Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata

    Science.gov (United States)

    Bribi, Noureddine; Algieri, Francesca; Rodriguez-Nogales, Alba; Garrido-Mesa, Jose; Vezza, Teresa; Maiza, Fadila; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Galvez, Julio

    2015-01-01

    Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis. PMID:26351518

  7. Study of Total Alkaloids from Rhizoma Coptis Chinensis on Experimental Gastric Ulcers

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To study the effects of total alkaloids (TA) extracted from Rhizoma Coptis Chinensis on experimental gastric ulcer models. Methods: Four kinds of experimental ulcer models were established respectively by water-immersion stress, intragastric ethanol, acetic acid erosion, and pylorus ligation. The anti-ulcer effects of TA were evaluated, and compared with that of berberine (Ber) and cimetidine(Cim). Results: TA showed significant inhibitory effects on ulcerative formation induced by water-immersion stress, intragastric ethanol, and pylorus l igation in dose-dependent manner, and showed therapeutic effect on acetic acid erosion-inducing ulcer, in comparison with the control group. The anti-ulcer activity of Ber was less than TA containing equal content of Ber. TA significantly reduced the free acidity, total acidity and total acid output, but didn't affect the gastric juice volume, gastric pepsin activity, adherent mucus quantity of stomach wall and free mucus dissolving in gastric juice. The suppressive activities of TA on gastric acid secretion didn't occur when it was administered into dodecadactylon at a dose of 360 mg/kg wt. Moreover,when compared with Cim, the inhibitory effect of TA on gastric acid secretion isn't proportional to the inhibitory effects on the formation of the 4 kinds of experimental ulcers. Conclusion: TA is a potent candidate in therapeutic drugs for treating gastric ulcer. Its anti-ulcer effective components and mechanism is not only related to Ber and inhibition of gastric acid, but also to other ingredients of TA and mechanism so far unknown.

  8. Total Synthesis of (±)-Hibiscone C

    OpenAIRE

    Ungureanu, Sinziana; Meadows, Maggie; Smith, Joel; Duff, David B.; Burgess, James M.; Goess, Brian C.

    2011-01-01

    A total synthesis of (±)- hibiscone C, one member of the furanosteroid family of natural products that also includes viridin and wortmannin, is reported. Two new pathways for formation of the key diacyl furan subunit are described.

  9. The First Total Synthesis of Isoliquiritin

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A first total synthesis of isoliquiritin was accomplished starting from p-hydroxy- benzaldehyde and 2,4-dihydroxyacetylphenone. The key step is condensation reaction. In synthetic process need not protect the hydroxy group of reacting substance.

  10. Validation of different methods of preparation of Adhatoda vasica leaf juice by quantification of total alkaloids and vasicine

    Directory of Open Access Journals (Sweden)

    Soni S

    2008-01-01

    Full Text Available Leaf of Adhatoda vasica ( Vasaka is an important drug of Ayurveda, prescribed as an expectorant. Quinazoline alkaloids present in the leaves are established as active principles. In Ayurveda, its leaf juice ( Vasa swarasa is incorporated in many formulations. Classical method for extracting the juice ( swarasa from the leaf is an elaborate process, which involves subjecting a bolus of crushed fresh leaf to heat followed by squeezing out the juice. Commercially, to prepare the juice of Vasaka , manufacturers have been adopting different methods other than the traditional method. In an effort to evaluate these modified processes phytochemically to identify the process which gives juice of the quality that is obtained by traditional method, in terms of its alkaloid content, we prepared the leaf juice by traditional Ayurvedic method, its modification by steaming of leaf to simulate the traditional method and other methods adopted by some manufacturers. These juice samples were evaluated for the total alkaloid content by spectrophotometric method and vasicine content by thin layer chromatography densitometric method using high performance thin layer chromatography. The high performance thin layer chromatography method was validated for precision, repeatability and accuracy. The total alkaloid content varied from 0.3 mg/ml to 5.93 mg/ml and that of vasicine content varied from 0.2 mg/ml to 5.64 mg/ml in the juice samples prepared by different methods. The present study revealed that steaming of fresh leaves under 15 lb pressure yielded same quantity of juice as the traditional bolus method (25 ml/100 g leaf and its total alkaloid content and vasicine content (4.05±0.12 and 3.46±0.06 mg/ml, respectively were very high when compared to the other methods, though the traditional method was found to give the best quality juice with highest amount of total alkaloids (5.93±0.55 mg/ml and vasicine (5.64±0.10 mg/ml content .

  11. Quantitative analysis of total retronecine esters-type pyrrolizidine alkaloids in plant by high performance liquid chromatography

    International Nuclear Information System (INIS)

    Pyrrolizidine alkaloids (PAs) are alkaloids which typically contain a necine (7-hydroxy-1-hydroxymethyl-6,7-dihydro-5H-pyrrolizidine) base unit, and they can be found in one third of the higher plants around the world. They are hepatotoxic, mutagenic and carcinogenic and pose a threat to human health and safety. A specific, quick and sensitive method is therefore needed to detect and quantify the PAs sometimes in trace amount in herbs, tea or food products. Based on high performance liquid chromatography with prior derivatization of the alkaloids using o-chloranil and Ehrlich's reagent, we report an improved method for quantitative analysis of the total amount of retronecine esters-type pyrrolizidine alkaloids (RET-PAs) in a plant extract. The total quantitation of RET-PAs is achieved because of a common colored retronecine marker, a 7-ethoxy-1-ethoxylmethyl retronecine derivative, is produced with all the different RET-PAs during the derivatization reaction. The chemical identity of the common retronecine marker was characterized on-line by positive mode electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The limit of detection using the improved method is 0.26 nmol mL-1 and the limit of quantitation is 0.79 nmol mL-1. The advantages of this method are much enhanced sensitivity in detection and quantitation, and, no restriction on the choice of RET-PA as a calibration standard. Application of the developed method to the quantitation of total RET esters-type PAs in Senecio scandens from different regions of China is also reported

  12. Antibacterial, antioxidant and cytotoxic studies of total saponin, alkaloid and sterols contents of decoction of Joshanda: identification of components through thin layer chromatography.

    Science.gov (United States)

    Khan, Haroon; Khan, Murad Ali; Abdullah

    2015-03-01

    The current study was aimed to assess antibacterial, antioxidant and cytotoxic activity of total saponin, alkaloid and sterol contents of Joshanda decoction followed by its constituent's analysis via thin layer chromatography (TLC). Saponins and alkaloids showed prominent antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumoniae whereas sterols only against S. aureus. Saponin and alkaloid contents of 97 and 108 µg/ml, respectively, showed prominent free radical scavenging activity against 1,1-diphenyl-2-picrylhidrazyl, with mild cytotoxicity in brine shrimp cytotoxic test. Under ultraviolet light at 254 nm, TLC of total saponins showed eight different compounds, total sterols comprising three while total alkaloids two compounds of various polarities. It is concluded that the various contents of Joshanda decoction possess outstanding susceptibility against bacteria implicating primarily upper respiratory tract infections augmented by strong antioxidant activity. PMID:23235996

  13. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

    Science.gov (United States)

    Plodek, Alois; Bracher, Franz

    2016-01-01

    Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades. PMID:26821033

  14. Total synthesis of palau'amine

    OpenAIRE

    Namba, Kosuke; Takeuchi, Kohei; Kaihara, Yukari; Oda, Masataka; Nakayama, Akira; Nakayama, Atsushi; YOSHIDA, Masahiro; Tanino, Keiji

    2015-01-01

    Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N–...

  15. A general strategy for the catalytic, highly enantio- and diastereoselective synthesis of indolizidine-based alkaloids.

    Science.gov (United States)

    Abels, Falko; Lindemann, Chris; Schneider, Christoph

    2014-02-10

    Sixteen indolizidine-based alkaloids (IBAs) that were isolated as poison constituents of the skin of frogs were synthesized in a highly flexible and stereoselective manner. As a key step, a three-component, organocatalytic, highly enantio- and diastereoselective vinylogous Mukaiyama-Mannich reaction was employed furnishing optically highly enriched butyrolactams as central intermediates on a multigram scale. The attached six-membered ring was constructed through cyclization of the pendant enoate moiety onto the pyrrolidine ring. The absolute configuration of the bridgehead chiral center and the adjacent 8-position was established in the initial vinylogous Mannich reaction, whereas the 3- and 5-substituents were introduced through organometallic addition at a late stage of the synthesis with full stereochemical control from the substrate. With this strategy, simple as well as even more complex alkaloids were accessible in good overall yields as single stereoisomers. These syntheses also served to establish the absolute and relative configuration of those IBAs that had never been synthesized before. PMID:24436076

  16. Total synthesis of insect antifeedant drimane sesquiterpenes.

    NARCIS (Netherlands)

    Jansen, B.J.M.

    1993-01-01

    The investigations described in this thesis deal with the total synthesis of sesquiterpenes of the drimane family, named for their widespread occurrence in the stem bark of South American Drimys species. These compounds contain the bicyclofarnesol nucleus 1 , which is invariably oxi

  17. Stereocontrolled total synthesis of hedyotol A.

    Science.gov (United States)

    Kawabe, Yusuke; Ishikawa, Ryo; Akao, Yusuke; Yoshida, Atsushi; Inai, Makoto; Asakawa, Tomohiro; Hamashima, Yoshitaka; Kan, Toshiyuki

    2014-04-01

    The total synthesis of hedyotol A (1), a natural product isolated from Hedyotis lawsoniae (DC.) Wight et Arn. (Rubiaceae), was accomplished in a highly stereocontrolled manner. Key steps include an L-proline-catalyzed cross-aldol reaction and the biomimetic construction of a furofuran lignan skeleton through a quinomethide intermediate. PMID:24660822

  18. Enantioselective Total Synthesis of (+)-Salvileucalin B

    OpenAIRE

    Levin, Sergiy; Nani, Roger R.; Reisman, Sarah E.

    2011-01-01

    An enantioselective total synthesis of the diterpenoid natural product (+)-salvileucalin B is reported. Key findings include a copper-catalyzed arene cyclopropanation reaction to provide the unusual norcaradiene core and a reversible retro-Claisen rearrangement of a highly functionalized norcaradiene intermediate.

  19. Total Synthesis of (-)-Nemorosone and (+)-Secohyperforin.

    Science.gov (United States)

    Sparling, Brian A; Tucker, James K; Moebius, David C; Shair, Matthew D

    2015-07-17

    A general strategy for the synthesis of polycyclic polyprenylated acylphloroglucinols is described in which a scalable, Lewis acid catalyzed epoxide-opening cascade cyclization is used to furnish common intermediate 4. The utility of this approach is exemplified by the total syntheses of both ent-nemorosone and (+)-secohyperforin, which were each accomplished in four steps from this intermediate. PMID:26125288

  20. Total Synthesis of balanol, Part 2

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Kelly, Nicholas; Tedenborg, Lars;

    1997-01-01

    A convergent enantioselective total synthesis of the natural product (-)-balanol (1) is described. In addition to benzophenone fragment 8, key intermediates are chiral bicyclic aziridine 3 and the corresponding epoxide 4, both of which undergo highly regio- and stereoselective nucleophilic ring...

  1. Enantioselective Total Synthesis of Plectosphaeroic Acid B

    OpenAIRE

    Jabri, Salman Y.; Overman, Larry E.

    2013-01-01

    The first total synthesis of a member of the plectosphaeroic acid family of fungal natural products is reported. Key steps include the late-stage formation of the hindered N6–C9″ bond and stereoselective introduction of the two methylthio substituents.

  2. Total synthesis of (S)-equol.

    Science.gov (United States)

    Heemstra, Jennifer M; Kerrigan, Sean A; Doerge, Daniel R; Helferich, William G; Boulanger, William A

    2006-11-23

    The first enantioselective total synthesis of (S)-equol is reported. The described route relies on an Evans alkylation to form the stereocenter and an intramolecular Buchwald etherification to generate the chroman ring. Key features of this method include its brevity, its scalability, and the low cost of starting materials. [reaction: see text]. PMID:17107042

  3. The total synthesis of pantocin B.

    Science.gov (United States)

    Sutton, A E; Clardy, J

    2000-02-10

    [reaction: see text] Pantocin B, an unusual antibiotic produced by Erwinia herbicola, effectively controls E. amylovora, the pathogen causing the plant disease fire blight. A total synthesis of pantocin B from L-alanine, glycine, and L-malic acid is reported. PMID:10814312

  4. The total synthesis of (-)-cryptocaryol A.

    Science.gov (United States)

    Dias, L C; Kuroishi, P K; de Lucca, E C

    2015-03-28

    A stereoselective total synthesis of (-)-cryptocaryol A (1) is described. Key features of the 17-step route include the use of three boron-mediated aldol reaction-reduction sequences to control all stereocenters and an Ando modification of the Horner-Wadsworth-Emmons olefination that permitted the installation of the Z double bond of the α-pyrone ring. PMID:25695350

  5. Preparation and In vitro Evaluation of Ethosomal Total Alkaloids of Sophora alopecuroides Loaded by a Transmembrane pH-Gradient Method

    OpenAIRE

    Zhou, Yan; Wei, Yuhui; Liu, Huanxiang; Zhang, Guoqiang; Wu, Xin’an

    2010-01-01

    A novel transmembrane pH gradient active loading method to prepare alkaloids binary ethosomes was developed in this work. Using this novel method, binary ethosomes containing total alkaloids extracted from Sophora alopecuroides (TASA) were prepared successfully at the temperature below the phase transition temperature (Tc) of the phosphatidyl choline (PC). Several factors affecting this method were investigated. The qualities of the TASA binary ethosomes were characterized by the shape, parti...

  6. First Total Synthesis of Gliomasolide C and Formal Total Synthesis of Sch-725674.

    Science.gov (United States)

    Seetharamsingh, B; Khairnar, Pankaj V; Reddy, D Srinivasa

    2016-01-01

    Syntheses of two 14-membered macrolides Sch-725674 and Gliomasolide C are described here. The first total synthesis of Gliomasolide C, the short synthesis of Sch-725674, and regioselective Wacker oxidation of internal olefin are the highlights of this disclosure. In addition, a key macrocycle with orthogonal functionalities was designed and synthesized on a gram scale for the generation of analogues. PMID:26633579

  7. Content determination exploration of uncaria total alkaloid%钩藤总生物碱的含量测定研究

    Institute of Scientific and Technical Information of China (English)

    许家洁; 于江波; 徐军; 仲崇琳; 杨美林

    2015-01-01

    Objective:To establish the method for content determination of uncaria total alkaloid.Methods:The contents of uncaria total alkaloid from uncaria total alkaloid extractive were determined by ultraviolet spectrophotometry.The contents of uncaria total alkaloid from uncaria total alkaloid extractive were determined by HPLC.Results:The incoming sample amount of uncaria total alkaloid was 0.168~0.840 μg,the peak area and incoming sample amount had good linear relationship(r=0.9995),the average recovery was 98.98%,RSD=1.31(n=5).Conclusion:This method was sensitive and accurate,which could be used for the content determination of uncaria total alkaloid.%目的:建立测定钩藤总生物碱含量的方法。方法:用紫外分光光度法测定钩藤总生物碱提取物中的钩藤总生物碱含量。采用高效色谱法测定钩藤总生物碱提取物中的钩藤碱含量。结果:钩藤碱的进样量0.168~0.840μg,其峰面积与进样量具有良好的线性关系(r=0.9995),平均回收率98.98%,RSD=1.31(n=5)。结论:该方法灵敏、准确,可用于钩藤总生物碱的含量测定。

  8. Total synthesis of (±)-antroquinonol d.

    Science.gov (United States)

    Sulake, Rohidas S; Jiang, Yan-Feng; Lin, Hsiao-Han; Chen, Chinpiao

    2014-11-21

    Total synthesis of (±)-antroquinonol D, which is isolated from very expensive and rarely found Antrodia camphorata and which has potential anticancer properties, was achieved from 4-methoxyphenol. In addition, a Michael addition to dimethoxy cyclohexadienones was studied. The main step involved chelation and substrate-controlled diastereoselective reduction of cyclohexenone and lactonization. Lactone synthesis facilitated the diastereoselective reduction of ketone, which help control the desired stereochemistry at the crucial stereogenic center in the natural product. Other key reactions in the synthesis involved a Michael addition of dimethyl malonate on cyclohexadienone, dihydroxylation, and Wittig olefination. A sesquiterpene side chain was synthesized through coupling with geranyl phenyl sulfide and Bouveault-Blanc reduction. PMID:25375772

  9. Total Alkaloids of Sophora alopecuroides Inhibit Growth and Induce Apoptosis in Human Cervical Tumor HeLa Cells In vitro

    Science.gov (United States)

    Li, Jian-Guang; Yang, Xiao-Yi; Huang, Wei

    2016-01-01

    Background: Uygur females of Xinjiang have the higher incidence of cervical tumor in the country. Alkaloids are the major active ingredients in Sophora alopecuroides, and its antitumor effect was recognized by the medical profession. Xinjiang is the main site of S. alopecuroides production in China so these plants are abundant in the region. Studies on the antitumor properties of total alkaloids of S. alopecuroides (TASA) can take full use of the traditional folk medicine in antitumor unique utility. Objectives: To explore the effects of TASA on proliferation and apoptosis of human cervical tumor HeLa cells in vitro. Materials and Methods: TASA was extracted, purified, and each monomer component was analyzed by high-performance liquid chromatography. The effect of TASA at different concentrations on the survival of HeLa cells was determined after 24 h using the Cell Counting Kit-8. In addition, cells were photographed using an inverted microscope to document morphological changes. The effect of TASA on apoptotic rate of HeLa cells was assessed by flow cytometry. Results: Monomers of TASA were found to be sophoridine, matrine, and sophocarpine. On treatment with 8.75 mg/ml of TASA, more than 50% of HeLa cells died, and cell death rate increased further with longer incubation. The apoptotic rates of HeLa cells in the experimental groups were 16.0% and 33.3% at concentrations of 6.25 mg/ml and 12.50 mg/ml, respectively. Conclusion: TASA can induce apoptosis in cervical tumor HeLa cells, and it has obvious inhibitory effects on cell growth. SUMMARY Total alkaloids of Sophora alopecuroides (TASA) exhibits anti-human cervical tumor propertiesMonomer component of TASA was analyzed by high-performance liquid chromatography, and its main effect component are sophoridine, matrine, and sophocarpineTASA inhibits growth and induces apoptosis in HeLa cells. Abbreviations used: TASA: Total alkaloids of S. alopecuroides, CCK-8: Cell Counting Kit-8, FBS: Fetal bovine serum, PBS

  10. Nineteen-step total synthesis of (+)-phorbol.

    Science.gov (United States)

    Kawamura, Shuhei; Chu, Hang; Felding, Jakob; Baran, Phil S

    2016-04-01

    Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to its intriguing chemical structure and the medicinal potential of phorbol esters. Access to useful quantities of phorbol and related analogues has relied on isolation from natural sources and semisynthesis. Despite efforts spanning 40 years, chemical synthesis has been unable to compete with these strategies, owing to its complexity and unusual placement of oxygen atoms. Purely synthetic enantiopure phorbol has remained elusive, and biological synthesis has not led to even the simplest members of this terpene family. Recently, the chemical syntheses of eudesmanes, germacrenes, taxanes and ingenanes have all benefited from a strategy inspired by the logic of two-phase terpene biosynthesis in which powerful C-C bond constructions and C-H bond oxidations go hand in hand. Here we implement a two-phase terpene synthesis strategy to achieve enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene. The purpose of this synthesis route is not to displace isolation or semisynthesis as a means of generating the natural product per se, but rather to enable access to analogues containing unique placements of oxygen atoms that are otherwise inaccessible. PMID:27007853

  11. Total Synthesis of (±)-Integrifolin.

    Science.gov (United States)

    Shimomaki, Katsuya; Kusama, Hiroyuki; Iwasawa, Nobuharu

    2016-07-11

    The total synthesis of (±)-integrifolin has been achieved for the first time through the stereoselective preparation of the bicyclo[5.3.0]decane skeleton based on the tungsten-catalyzed cyclization of acyclic trienynes under photoirradiation conditions. Further key transformations of the cyclized product are the Tamao oxidation through cyclic silyl ether, the introduction of two oxygen functionalities by the oxidation of the diene and the construction of three exo-methylene moieties. PMID:27147582

  12. Total Synthesis and Stereochemical Assignment of Callyspongiolide.

    Science.gov (United States)

    Zhou, Jingjing; Gao, Bowen; Xu, Zhengshuang; Ye, Tao

    2016-06-01

    Total synthesis of four callyspongiolide stereoisomers led to unambiguous assignment of relative and absolute stereochemistry of the natural product. Key features of the convergent, fully stereocontrolled route include the use of Krische allylation, Kiyooka Aldol reaction, Kociénski-Julia olefination, Still-Gennari olefination, Yamaguchi macrocyclization, and Sonogashira coupling reaction. Biological evaluation of the synthesized compounds against an array of cancer cells revealed that the stereochemistry of the macrolactone core played an important role. PMID:27227371

  13. Total synthesis of (+)-antroquinonol and (+)-antroquinonol D.

    Science.gov (United States)

    Sulake, Rohidas S; Chen, Chinpiao

    2015-03-01

    The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate. PMID:25679542

  14. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Alessandra Mirtes Marques Neves Gonçalves

    2014-07-01

    Full Text Available Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.

  15. Synthesis of Pandamarilactone-1

    OpenAIRE

    Seah, Kang Yee; Macnaughton, Sarah J.; Dallimore, Jonathan W. P.; Robertson, Jeremy

    2014-01-01

    The first total synthesis of pandamarilactone-1, an alkaloid of Pandanus amaryllifolius, is reported. The nine-step synthesis features furan oxidation with singlet oxygen and then spiro-N,O-acetalization and elimination to generate the natural product and further Pandanus alkaloids, pandamarilactonines A–D.

  16. Bacterial Alkaloids Prevent Amoebal Predation.

    Science.gov (United States)

    Klapper, Martin; Götze, Sebastian; Barnett, Robert; Willing, Karsten; Stallforth, Pierre

    2016-07-25

    Bacterial defense mechanisms have evolved to protect bacteria against predation by nematodes, predatory bacteria, or amoebae. We identified novel bacterial alkaloids (pyreudiones A-D) that protect the producer, Pseudomonas fluorescens HKI0770, against amoebal predation. Isolation, structure elucidation, total synthesis, and a proposed biosynthetic pathway for these structures are presented. The generation of P. fluorescens gene-deletion mutants unable to produce pyreudiones rendered the bacterium edible to a variety of soil-dwelling amoebae. PMID:27294402

  17. Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach.

    Science.gov (United States)

    Chen, Xiaoming; Duan, Shengguo; Tao, Cheng; Zhai, Hongbin; Qiu, Fayang G

    2015-01-01

    The structurally complex alkaloid gelsemine was previously thought to have no significant biological activities, but a recent study has shown that it has potent and specific antinociception in chronic pain. While this molecule has attracted significant interests from the synthetic community, an efficient synthetic strategy is still the goal of many synthetic chemists. Here we report the asymmetric total synthesis of (+)-gelsemine, including a highly diastereoselective and enantioselective organocatalytic Diels-Alder reaction, an efficient intramolecular trans-annular aldol condensation furnishing the prolidine ring and establishing the configuration of the C20 quaternary carbon stereochemical centre. The entire gelsemine skeleton was constructed through a late-stage intramolecular SN2 substitution. The enantiomeric excess of this total synthesis is over 99%, and the overall yield is around 5%. PMID:25995149

  18. Total synthesis of human beta-lipotropin.

    OpenAIRE

    Blake, J; Li, C. H.

    1983-01-01

    The total synthesis of human beta-lipotropin has been accomplished by the new segment-coupling method in aqueous solution. The peptides Ac-Arg-beta-lipotropin-(61-89) (I) and [GlyS60]-beta-lipotropin-(1-60) (II) were synthesized by the solid-phase method. Reaction of peptide I with citraconic anhydride followed by brief digestion with trypsin to remove the acetylarginyl group, gave Ia. Reaction of peptide II with citraconic anhydride gave the citraconyl peptide IIa. Ia and IIa were coupled to...

  19. Total synthesis of insect antifeedant drimane sesquiterpenes.

    OpenAIRE

    Jansen, B.J.M.

    1993-01-01

    The investigations described in this thesis deal with the total synthesis of sesquiterpenes of the drimane family, named for their widespread occurrence in the stem bark of South American Drimys species. These compounds contain the bicyclofarnesol nucleus 1 , which is invariably oxidized at C-11 and/or C-12 and often at other sites as well (see figure 8.1).A few rearranged drimanes, e.g., (+)-colorata-4(13),8-dienolide 6 , and (-)-muzigadial 7 , are also isolated from natural products. The re...

  20. A novel class of H3 antagonists derived from the natural product guided synthesis of unnatural analogs of the marine bromopyrrole alkaloid dispyrin

    OpenAIRE

    Kennedy, J. Phillip; Conn, P. Jeffrey; Lindsley, Craig W.

    2009-01-01

    This Letter describes the natural product guided synthesis of unnatural analogs of the marine bromopyrrole alkaloid dispyrin, and the resulting SAR of H3 antagonism. Multiple rounds of iterative parallel synthesis improved human H3 IC50 ~33-fold, and afforded a new class of H3 antagonists based on the novel bromotyramine core of dispyrin.

  1. The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells.

    Science.gov (United States)

    Bonjean, K; De Pauw-Gillet, M C; Defresne, M P; Colson, P; Houssier, C; Dassonneville, L; Bailly, C; Greimers, R; Wright, C; Quetin-Leclercq, J; Tits, M; Angenot, L

    1998-04-14

    Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host-mediated biological activities, including antibacterial, antiviral, and antimalarial properties. To date, the molecular basis for its diverse biological effects remains largely uncertain. Several lines of evidence strongly suggest that DNA might correspond to its principal cellular target. Consequently, we studied the strength and mode of binding to DNA of cryptolepine by means of absorption, fluorescence, circular, and linear dichroism, as well as by a relaxation assay using DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to reveal that the alkaloid binds tightly to DNA and behaves as a typical intercalating agent. In DNAase I footprinting experiments it was found that the drug interacts preferentially with GC-rich sequences and discriminates against homo-oligomeric runs of A and T. This study has also led to the discovery that cryptolepine is a potent topoisomerase II inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA covalent complexes and stimulates the cutting of DNA at a subset of preexisting topoisomerase II cleavage sites. Taking advantage of the fluorescence of the indoloquinoline chromophore, fluorescence microscopy was used to map cellular uptake of the drug. Cryptolepine easily crosses the cell membranes and accumulates selectively into the nuclei rather than in the cytoplasm of B16 melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is also shown that the alkaloid is more potent at inhibiting DNA synthesis rather than RNA and protein synthesis. Altogether, the results provide direct evidence that DNA is the primary target of cryptolepine and suggest that this alkaloid is a valid candidate for the development of tumor

  2. Bioinspired Collective Syntheses of Iboga-Type Indole Alkaloids.

    Science.gov (United States)

    Zhao, Gaoyuan; Xie, Xingang; Sun, Haiyu; Yuan, Ziyun; Zhong, Zhuliang; Tang, Shouchu; She, Xuegong

    2016-05-20

    We present the application of a bioinspired collective synthesis strategy in the total syntheses of seven iboga-type indole alkaloids: (±)-tabertinggine, (±)-ibogamine, (±)-ibogaine, (±)-ibogaine hydroxyindolenine, (±)-3-oxoibogaine hydroxyindolenine, (±)-iboluteine, and (±)-ervaoffines D. In particular, tabertinggine and its congeners serve as iboga precursors for the subsequent biomimetic transformations into other iboga-type alkaloids. PMID:27160167

  3. Total synthesis of diterpenoid steenkrotin A.

    Science.gov (United States)

    Pan, Saiyong; Xuan, Jun; Gao, Beiling; Zhu, An; Ding, Hanfeng

    2015-06-01

    A concise and diastereoselective total synthesis of the diterpenoid (±)-steenkrotin A is described for the first time. The strategy mainly features three key ring formations: 1) a rhodium-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction to build up the tetrahydrofuran subunit; 2) sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations to construct the [5,7] spirobicyclic skeleton; and 3) an intramolecular aldol condensation/vinylogous retro-aldol/aldol sequence to form the final six-membered ring with inversion of the relative configuration at the C7 position. PMID:25891977

  4. The Total Synthesis of Inostamycin A.

    Science.gov (United States)

    Yu, Guangri; Jung, Byunghyuck; Lee, Hee-Seung; Kang, Sung Ho

    2016-02-12

    The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency. PMID:26800259

  5. Total Synthesis of Rubriflordilactone B.

    Science.gov (United States)

    Yang, Peng; Yao, Ming; Li, Jian; Li, Yong; Li, Ang

    2016-06-01

    Taking advantage of a 6π electrocyclization-aromatization strategy, we accomplished the first and asymmetric total synthesis of rubriflordilactone B, a heptacyclic Schisandraceae bisnortriterpenoid featuring a tetrasubstituted arene moiety. The left-hand fragment was accessed through a chiral-pool-based route, and linked to the right-hand fragment by a Sonogashira coupling. The cis geometry of the electrocyclization substrates was established by hydrogenation or hydrosilylation of the alkyne. An electrocyclization-aromatization sequence finally built the multisubstituted arene. The hydrosilylation approach was of significant advantage in terms of reaction scale, reproducibility, and intermediate stability. The structure of synthetic rubriflordilactone B was validated by X-ray crystallographic analysis, and found to be consistent with that reported for the authentic natural product based on an independent X-ray crystallographic analysis. However, obvious differences in the NMR spectra of the synthetic and authentic samples suggest that the authentic samples subjected to X-ray crystallography and NMR spectroscopy were two different compounds. PMID:27121027

  6. Total Synthesis of a Diacetonide Derivative of Thuggacin A.

    Science.gov (United States)

    Yadav, Jhillu S; Dutta, Palash

    2016-03-01

    A highly stereoselective total synthesis of the diacetonide derivative of the antibiotic thuggacin A has been described. The synthesis features the stereoselective Stille cross-coupling reaction to set up the whole carbon framework, aldol condensation to construct the highly substituted conjugated diene, non-Evans syn aldol, CBS reduction, Hantzsch's thiazole synthesis, Horner-Wadsworth-Emmons reaction, and Shiina's macrolactonization. PMID:26856208

  7. Concise total synthesis of water soluble metatacarboline A, C, D, E and F and its anticancer activity.

    Science.gov (United States)

    Naveen, Badher; Mudiraj, Anwita; Khamushavalli, Geeviman; Babu, Phanithi Prakash; Nagarajan, Rajagopal

    2016-05-01

    The simple, concise, protecting group free and first total synthesis of Metatacarboline alkaloids (abbreviated as Mc) Mc A, C, D, E and F are reported. The core structure of metatacarboline alkaloids has been constructed by the classical Wittig reaction as key step from easily accessible starting materials with 40-75% overall yields. These synthesized compounds have been subjected to evaluate for their anticancer activity using C6 glioma cell lines. Mc D and Mc F showed significant antiproliferative activity, which was confirmed by MTT and Clonogenic assay. FACS analysis showed that Mc D and Mc F arrested the cell cycle at sub G0/G1 and G2/M phase of cell cycle respectively. Further, Western blot analysis and immunohistochemistry of Mc D treated cells revealed activation of caspase dependent downstream signaling which led to apoptosis. PMID:26927685

  8. Total Synthesis of the Cyanolide A Aglycon

    OpenAIRE

    Gesinski, Michael R.; Rychnovsky, Scott D.

    2011-01-01

    The synthesis of the potent molluscicide, cyanolide A, has been achieved in 10 steps without the use of protecting groups. The synthesis features a key Sakurai macrocyclization/dimerization reaction that simultaneously forms both tetrahydropyran rings and the macrocycle of the natural product.

  9. The total synthesis of cannabisin G

    Directory of Open Access Journals (Sweden)

    YAMU XIA

    2010-12-01

    Full Text Available A convenient method for the synthesis of lignanamide cannabisin G, starting from vanillin, was developed. The convergent synthesis was based on the Stobbe reaction as C–C bond-forming steps to give the skeleton of lignan, which was condensed with a derivative of tyramine to obtain synthetic cannabisin G for the first time.

  10. Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel

    OpenAIRE

    Sun, Liang; Veith, Jean M.; Pera, Paula; Bernacki, Ralph J.; Ojima, Iwao

    2010-01-01

    Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, i.e., REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to ev...

  11. Efficient synthesis of the C/D rings of atisine-type C20-diterpenoid alkaloids

    Institute of Scientific and Technical Information of China (English)

    De Lin Chen; Feng Peng Wang

    2012-01-01

    A bicyclo[2.2.2]octane C/D ring system,with a lactonic ring at C-8 and C-9,of the atisine-type C20-diterpenoid alkaloids,was successfully synthesized,using an oxidative dearomatization/intramolecular Diels-Alder reaction.

  12. Total synthesis of (±)-divanillyltetrahydrofuran ferulate

    Indian Academy of Sciences (India)

    Ya-Mu Xia; Jia You; Qi Wang

    2010-05-01

    A convenient method for the synthesis of sesquilignan threo- and erythro-(±)-divanillyltetrahydrofuran ferulate is described. The synthesis was based on a unified synthetic strategy involving two Stobbe condensations to give the skeleton of lignan, and then reduction reaction to form meso- and threo-(±)-secoisolanciresinol. meso- and threo-(±)-secoisolanciresinol were separated by flash column chromatography, followed by intramolecular reaction with TsCl to afford the key intermediate meso- or threo-(±)-shonanin, then condensation with ferulaic acid to obtain sesquilignan threo- or its analogue erythro-(±)-divanillyltetrahydrofuran ferulate.

  13. Total Synthesis of (±)-Mitorubrinic Acid

    OpenAIRE

    Marsini, Maurice A.; Gowin, Kristoffer M.; Pettus, Thomas R. R.

    2006-01-01

    (±)-Mitorubrinic acid, a member of the azaphilone family of natural products, has been constructed in 12 steps. Key aspects of the synthesis include elaboration and oxidative dearomatization of an isocoumarin intermediate to provide the azaphilone nucleus with a disubstituted, unsaturated carboxylic acid side chain.

  14. Ultrasound Bath-assisted Enzymatic Hydrolysis Procedures as Extraction Technology of the Total Alkaloid from Portulaca%超声辅助酶解法提取马齿苋总生物碱

    Institute of Scientific and Technical Information of China (English)

    谢彦

    2011-01-01

    利用超声波辅助纤维素酶解法对马齿苋中的总生物碱进行了提取,并用溴甲酚绿比色法与正交试验结合的方法确定了最佳提取条件.%Total alkaloid was extracted from portulaca by ultrasound bath-assisted enzymatic hydrol- ysis procedures, through bromine cresol green colorimetric determinating alkaloid content. Combined with the orthogonal experiment research, best condition of total portulaca alkaloid by ultrasound bath-as- sisted enzymatic hydrolysis procedures is determined.

  15. Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency

    Directory of Open Access Journals (Sweden)

    Sebastien Boucle

    2015-01-01

    Full Text Available This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1–11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

  16. First total synthesis of prasinic acid and its anticancer activity.

    Science.gov (United States)

    Chakor, Narayan; Patil, Ganesh; Writer, Diana; Periyasamy, Giridharan; Sharma, Rajiv; Roychowdhury, Abhijit; Mishra, Prabhu Dutt

    2012-11-01

    The first total synthesis of prasinic acid is being reported along with its biological evaluation. The ten step synthesis involved readily available and cheap starting materials and can easily be transposed to large scale manufacturing. The crucial steps of the synthesis included the formation of two different aromatic units (7 and 9) and their coupling reaction. The synthetic prasinic acid exhibited moderate antitumor activity (IC(50) 4.3-9.1 μM) in different lines of cancer cells. PMID:23031589

  17. Total Synthesis of the Antitumor Antibiotic Basidalin.

    Science.gov (United States)

    Acosta, Jaime A M; Muddala, Ramesh; Barbosa, Luiz C A; Boukouvalas, John

    2016-08-01

    The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal. PMID:27347696

  18. Study Toward the Total Synthesis of Pyrenophorin

    OpenAIRE

    Everaldo F. Santos Filho; Italo Ricardo S. Araujo; Mirela Garcia; Jefferson L. Princival

    2012-01-01

    Macrodiolides are macrocyclic compounds containing two ester groups in a cyclic chain. Of this class of compounds, Pyrenophorin (1) shows antifungal activity, and is produced from the pathogenic fungus Pyrenophora avenae. As this substance, derived from nature, is isolated in small quantities, an asymmetric synthesis using a simple and efficient methodology would be of great interest. The proposed synthetic route starts with the protection of propargyl alcohol 3 using DHP and feldspar as cata...

  19. Asymmetric Total Synthesis of Soraphen A: a Flexible Alkyne Strategy**

    OpenAIRE

    Trost, Barry M.; Sieber, Joshua D.; Qian, Wei; Dhawan, Rajiv; Ball, Zachary T.

    2009-01-01

    The alkyne functional group can be a valuable handle for organic synthesis since the alkyne can function both as a nucleophile or as an electrophile when activated with an appropriate metal catalyst. Herein, we exploit this dual nature of the alkyne moiety for the concise total synthesis of the natural product soraphen A.

  20. First total synthesis of (+/-)-3-hydroxy-11-norcytisine

    DEFF Research Database (Denmark)

    Yohannes, Daniel; Hansen, Camilla Petrycer; Akireddy, Srinivasa Rao; Hauser, Terry A; Kiser, Melanie N; Gurnon, Nicholas J; Day, Cynthia S; Bhatti, Balwinder; Caldwell, William S

    2008-01-01

    The first total synthesis of the natural product 3-hydroxy-11-norcytisine ( 1), structurally related to cytisine ( 2), a benchmark ligand at neuronal nicotinic acetylcholine receptors (NNRs), has been achieved. The synthesis permits the unambiguous confirmation of the structure originally propose...

  1. Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

    Science.gov (United States)

    He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli

    2016-05-01

    This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches. PMID:26848702

  2. 小花棘豆总生物碱抑菌作用的研究%Study on Bacteriostasis Efficiency of Total Alkaloids in Oxytropis glabra DC

    Institute of Scientific and Technical Information of China (English)

    王帅; 李怀志; 马明; 张玲; 马春晖

    2012-01-01

    [目的]研究小花棘豆总生物碱的抑菌作用.[方法]通过体外抑菌试验研究小花棘豆总生物碱的抑菌活性、最小抑菌浓度(MIC)、最小杀菌浓度(MBC)和影响小花棘豆总生物碱抑菌效果的因素.[结果]小花棘豆总生物碱对金黄色葡萄球菌、乳房链球菌、化脓链球菌和枯草芽孢杆菌有抑菌作用;其对乳房链球菌和化脓链球菌的MIC为6.3 mg/mL,对金黄色葡萄球菌的MIC为1.6 mg/mL,对枯草芽孢杆菌的MIC为0.8 mg/mL.生物碱在不同pH值下的抑菌活性发生变化;高温使其抑菌活性消失;紫外照射对其稳定性没有影响.[结论]小花棘豆总生物碱对部分革兰氏阳性菌有较好的抑菌作用.%[ Objective ] The purpose of this project aim to study the antimicrobial activities of total alkaloids for Oxytropis glabra DC. [Method] Through bacteriostasis experiments in vitro, antimicrobial activities of total alkaloids for Oxytropis glabra DC on bacteriostasis efficiency, minimal inhibitory concentration, minimal bactericidal concentration, and environmental effect were studied . [Result]The result showed that alkaloid of Oxytropis glabra DC had fairly bacteriostasis for Staphylococcus aureus, Streptococcus uberis, Streptococcus pyogene, Bacillus subtilis; the MIC for Streptococcus uberis and Streptococcus pyogene was 6. 3 mg/Ml, the MIC for Staphylococcus aureus was 1. 6 mg/Ml, the MIC for Bacillus subtilis was 0. 8 mg/ Ml. The diversity of bacteriostasis efficiency of alkaloid happened in different power of hydrogen; the bacteriostasis material has bad heat stability; ultraviolet ray treatment does not affect its stability. [Conclusion] Total alkaloids of Oxytropis glabra DC had obvious bacteriostasis effect for Gram - positive bacteria.

  3. Study Toward the Total Synthesis of Pyrenophorin

    Directory of Open Access Journals (Sweden)

    Everaldo F. Santos Filho

    2012-06-01

    Full Text Available Macrodiolides are macrocyclic compounds containing two ester groups in a cyclic chain. Of this class of compounds, Pyrenophorin (1 shows antifungal activity, and is produced from the pathogenic fungus Pyrenophora avenae. As this substance, derived from nature, is isolated in small quantities, an asymmetric synthesis using a simple and efficient methodology would be of great interest. The proposed synthetic route starts with the protection of propargyl alcohol 3 using DHP and feldspar as catalyst. Compound 5 obtained in this reaction was then subjected to acid-base reaction between the acetylenic proton and 1 eq. n-BuLi, leading to formation of the acetylide 5A. The 1,2- addition reaction between 5A and g-valerolactone (6 leads to the formation of alkinone 7 in 67% yield. Subsequently, compound 7 was subjected to a ketalization reaction using the same feldspar catalyst. Ketal 8 was formed under concomitant removal of the THP group. The product of this reaction (8 was then submitted to a reduction reaction of the triple bond to form olefin 9 with E configuration. Currently, the conditions for obtaining 10 by oxidation using Jones reagent, are being optimized. Compound 10,    obtained as described, is being subjected to a macrolactonization reaction. Various conditions including the use of enzymes are being studied. In addition, a study involving the enantioselective synthesis of (R,R-(--pyrenophorin, using enzymatic kinetic resolution of the racemic mixture of compound 8, is in progress in the group

  4. The synthesis of 3H-putrescine and subsequent biosynthesis of 3H-jacobine, a pyrrolizidine alkaloid from Senecio jacobaea

    International Nuclear Information System (INIS)

    A new method was developed for the preparation of tritiated putrescine dihydrochloride ([2,3-3H]-1,4-diaminobutane dihydro-chloride) from succinonitrile (1,4-butanedinitrile) and 3H2O, with a radiochemical yield of 16%. Tritiated jacobine and other pyrrolizidine alkaloids were then biosynthesized in Senecio jacobaea using 3H-putrescine-2HCl as the precursor with a radiochemical yield of 0.9% into total pyrrolizidine alkaloids. Jacobine accounted for 36% of the total. This synthetic method provides a relatively inexpensive source for the preparation of these labelled compounds. (author)

  5. Total Synthesis of (±)-Strychnine via a [4+2]-Cycloaddition/Rearrangement Cascade

    OpenAIRE

    Zhang, Hongjun; Boonsombat, Jutatip; Padwa, Albert

    2007-01-01

    A new strategy for the synthesis of the Strychnos alkaloid (±)-strychnine has been developed and is based on an intramolecular [4+2]-cycloaddition/rearrangement cascade of an indolyl substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide.

  6. Study on the determination method of total alkaloids in Tinospora sinensis caulis%宽筋藤总生物碱含量测定方法研究

    Institute of Scientific and Technical Information of China (English)

    迟森森; 韩丹; 刘斌

    2015-01-01

    Objective To establish a method for the determination of total alkaloids in Tinospora sinensis caulis .Method The content of total alkaloids was determined ,and hydrochloric jatrorrhizine was selected as a reference substance .Results Hydrochloric jatrorrhizine had a good linear relationship with the absorbance in the range of 0 .001 1‐0 .006 5 mg · mL-1 and the regression equation was Y=14 .747 X-0 .010 7 (r=0 .999 5) .The average recovery for hydrochloric jatrorrhizine was 100 .4% ,RSD=2 .0% (n=6) .Conclusion The contents determination of the total alkaloids for sixteen batches of medicinal materials showed that the method was easy to operate and accurate ,which could be used for the determination of the total alkaloids in Tinospora sinensis caulis .%目的:建立宽筋藤药材中总生物碱的含量测定方法。方法以盐酸药根碱为对照品,采用紫外‐可见分光光度法测定宽筋藤总生物碱的含量,测定波长为430 nm。结果盐酸药根碱在0.0011~0.0065 mg · mL -1范围内与吸光度呈良好线性关系,回归方程:Y=14.747X-0.0107(r=0.9995)。盐酸药根碱平均回收率为100.4%,RSD=2.0%(n=6)。结论16批宽筋藤药材总生物碱含量测定结果表明,所建立的方法简便、准确,可用于宽筋藤药材总生物碱的含量测定。

  7. 宽筋藤总生物碱含量测定方法研究%Study on the determination method of total alkaloids in Tinospora sinensis caulis

    Institute of Scientific and Technical Information of China (English)

    迟森森; 韩丹; 刘斌

    2015-01-01

    Objective To establish a method for the determination of total alkaloids in Tinospora sinensis caulis .Method The content of total alkaloids was determined ,and hydrochloric jatrorrhizine was selected as a reference substance .Results Hydrochloric jatrorrhizine had a good linear relationship with the absorbance in the range of 0 .001 1‐0 .006 5 mg · mL-1 and the regression equation was Y=14 .747 X-0 .010 7 (r=0 .999 5) .The average recovery for hydrochloric jatrorrhizine was 100 .4% ,RSD=2 .0% (n=6) .Conclusion The contents determination of the total alkaloids for sixteen batches of medicinal materials showed that the method was easy to operate and accurate ,which could be used for the determination of the total alkaloids in Tinospora sinensis caulis .%目的:建立宽筋藤药材中总生物碱的含量测定方法。方法以盐酸药根碱为对照品,采用紫外‐可见分光光度法测定宽筋藤总生物碱的含量,测定波长为430 nm。结果盐酸药根碱在0.0011~0.0065 mg · mL -1范围内与吸光度呈良好线性关系,回归方程:Y=14.747X-0.0107(r=0.9995)。盐酸药根碱平均回收率为100.4%,RSD=2.0%(n=6)。结论16批宽筋藤药材总生物碱含量测定结果表明,所建立的方法简便、准确,可用于宽筋藤药材总生物碱的含量测定。

  8. Total Synthesis of (+)-Rubriflordilactone A.

    Science.gov (United States)

    Goh, Shermin S; Chaubet, Guilhem; Gockel, Birgit; Cordonnier, Marie-Caroline A; Baars, Hannah; Phillips, Andrew W; Anderson, Edward A

    2015-10-19

    Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products. PMID:26337920

  9. First total synthesis of (±)-sepicanin A

    Institute of Scientific and Technical Information of China (English)

    Jin Hui Yang; Wen Qian Huang; Jun Shan Luo; Dong Dong Guo; Yu Heng Zhang; Hong Jun Li

    2012-01-01

    A facile approach for the first total synthesis of naturally occurring geranylated flavanoids sepicanin A has been obtained with total yield 16% starting from 2,4,6-trihydroxyacetophenone after four steps.The key step was the protic acids (HCl or p-TsOH)-catalyzed benzopyrone formation in a protic polar solvent by deprotection and cyclization of chalcone in one step.

  10. First total synthesis of (±)-abyssinoflavanone V

    Institute of Scientific and Technical Information of China (English)

    Jin Hui Yang; Yan Min Zhao; Cong Bin Ji

    2008-01-01

    The total synthesis of (±)-abyssinoflavanone V was first achieved through C-prenylation, selective protection of phenolic hydroxyl group, aldol condensation, cyclization and deprotection starting from cheap 4-hydroxybenzaldehyde and 2,4,6-trihydroxyacetophenone, with total yield 24%. All structures of new compounds were confirmed by IR, 1H NMR and MS.

  11. Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Zhibin Li

    2015-07-01

    Full Text Available A series of β-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35% than commercial antiviral agent validamycin (36.4%; compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%. Some of the alkaloids and their derivatives (compounds F4 and F25 exhibited broad-spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs.

  12. Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity.

    Science.gov (United States)

    Stavrinides, Anna; Tatsis, Evangelos C; Caputi, Lorenzo; Foureau, Emilien; Stevenson, Clare E M; Lawson, David M; Courdavault, Vincent; O'Connor, Sarah E

    2016-01-01

    Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold. PMID:27418042

  13. The Total Synthesis of (+)-Pleuromutilin and Novel Analogues

    OpenAIRE

    Fazakerley, Neal James

    2014-01-01

    The increasing emergence of multi-drug-resistant microorganisms has led the World Health Organisation to plead for action to be taken against antimicrobial resistance. The fungal secondary metabolite (+)-pleuromutilin displays antibacterial activity with a novel mode of action: pleuromutilin derivatives bind to functionally important nucleotides within the peptidyl transfer centre of the prokaryotic ribosome and inhibit bacterial protein synthesis.The first non-racemic total synthesis of the ...

  14. Total synthesis and stereochemical revision of (+)-aeruginosin 298-A.

    Science.gov (United States)

    Wipf, P; Methot, J L

    2000-12-28

    [structure:see text] Novel routes toward both enantiomers of the bicyclic proline surrogate 2-carboxy-6-hydroxyoctahydroindole, i.e., Choi, were developed on the basis of the oxidative cyclization of L-tyrosine. Synthesis of the proposed sequence of (+)-aeruginosin 298-A did not provide the natural product. Incorporation of a D-leucine residue, in contrast, led to the total synthesis of this thrombin inhibitor. PMID:11150202

  15. Total Synthesis and Absolute Configuration of the Marine Norditerpenoid Xestenone

    Directory of Open Access Journals (Sweden)

    Hiroaki Miyaoka

    2009-11-01

    Full Text Available Xestenone is a marine norditerpenoid found in the northeastern Pacific sponge Xestospongia vanilla. The relative configuration of C-3 and C-7 in xestenone was determined by NOESY spectral analysis. However the relative configuration of C-12 and the absolute configuration of this compound were not determined. The authors have now achieved the total synthesis of xestenone using their developed one-pot synthesis of cyclopentane derivatives employing allyl phenyl sulfone and an epoxy iodide as a key step. The relative and absolute configurations of xestenone were thus successfully determined by this synthesis.

  16. Study On Extraction Processes Of Total Alkaloids From Ramulus Uncariae Cum Uncis%钩藤总生物碱提取工艺研究

    Institute of Scientific and Technical Information of China (English)

    窦月; 周洪雷; 蔡梅超; 查慧敏

    2011-01-01

    目的:优选钩藤总生物碱的提取工艺.方法:以钩藤总碱含量和提取液千膏率为综合评价指标,对乙醇用量、浓度、提取时间及次数四因素进行正交考察.结果:钩藤总碱的最佳提取工艺为10倍量75%乙醇提取3次,提取时间2h.结论:提取工艺可稳定可行.%Objective: Investigate the best extract artwork of expressed total alkaloids from Ramulus Uncariae Cum Uncis. Methods: The orthogonal design was adopted with extractive yield and the content of total alkaloids as indices. Four factors were studied in this experiment, including the alcohol consumption, alcohol concentration, time of extraction, and times of extraction. Results:The best extract process is extract 3 times with 10 times 75% alcohol,each time for 2h. Conclusion:This extract process is stable and feasible.

  17. A comparative study on analytical method of total alkaloids from cortex Phellodendri amurens by reversed phase high performance liquid chromatography (RP-HPLC and pressurized capillary electrochromatography (pCEC

    Directory of Open Access Journals (Sweden)

    Bo Yang

    2011-02-01

    Full Text Available A pressurized capillary electrochromatography (pCEC method with post-column detection cell has been developed for the analysis of total alkaloids of cortex Phellodendron amurense Rupr., Rutaceae. The separation of total alkaloids (berberine, palmatine, oatrorrhizine, magnoflorine, phellodendrine, candicine, menisperine was optimized by compositions of the mobile phase, ionic strength of buffers, pH value, and applied voltage. Separation of total alkaloids was achieved within 11 min by using a mobile phase of Na2HPO4-citric acid solution-acetonitrile (pH 4.00; 3 mM (60:40, v/v and applying a voltage of -10 kV. This method showed satisfactory retention times and peak shapes. Meanwhile, a reversed phase high performance liquid chromatography (RP-HPLC has also been established for the separation of total alkaloids extracted from cortex Phellodendri amurens. Baseline separation of total alkaloids was achieved within 25 min by using a mobile phase of acetonitrile-0.1% phosphoric acid with 0.1 g sodium dodecanesulphonate per 100 mL (35:65, v/v. Compared to conventional RP-HPLC, pCEC led to higher column efficiency, less consumption of reagent, and shorter analysis time.

  18. Mechanism of Lipid-Lowering Effect of Paniculata Total Alkaloids%布渣叶总生物碱降血脂作用机制研究

    Institute of Scientific and Technical Information of China (English)

    冯亮

    2015-01-01

    目的 探讨布渣叶总生物碱降血脂作用机制研究. 方法 采用高脂饲料构建高脂血症的大鼠动物模型, 采用灌胃的形式给予不同浓度的布渣叶总生物碱, 通过检测大鼠载脂蛋白、 相关酶类及活性物质, 初步探讨布渣叶总生物碱的降脂作用机制. 结果 布渣叶总生物碱可升高载脂蛋白AI ( ApoAI) , ApoAI/载脂蛋白B ( ApoB) 的比值, 与模型组相比差异具有统计学意义 (P<0. 05); 提高超氧化物歧化酶 (SOD) 的活性, 降低丙二醛 (MDA) 的含量, 与模型组相比差异具有统计学意义 (P<0. 05); 提高卵磷脂胆固醇酰基转移酶 (LCAT) 的活性, 提高一氧化氮 (NO) 的水平, 降低C反应蛋白 (CRP), 且组间相比具有统计学差异 (P<0. 05). 结论 布渣叶总生物碱通过升高高密度脂蛋白胆固醇升高ApoAI, 激活LCAT, 从而促进胆固醇的逆转运, 提高SOD活性, 增强机体康脂质过氧化能力, 促进NO生成, 改善血管内皮功能,具有从多方位调节血脂的作用.%Objective To investigate the mechanism of lipid-lowering effect of paniculata total alkaloids. Methods Animal models of hyperlipidemia rats were constructed by using the high-fat diet. Different concentrations of paniculata total alkaloids were ad-ministered in the form of gavage. Lipid-lowering effect of paniculata total alkaloids was studied by detecting rat apolipoprotein, associ-ated enzymes and active substances. Results The paniculata total alkaloids increased apolipoprotein AI ( ApoAI) , ApoAI / ratio of apolipoprotein B (ApoB). There was statistically significant difference compared with that of the model group (P<0. 05), it also in-creased superoxide dismutase ( SOD) activity and decreased malondialdehyde ( MDA) content. They were significantly different com-pared with those of the model group (P<0. 05), it improved lecithin cholesterol acyltransferase (LCAT) activity, increased Nitric ox-ide (NO) levels and reduced C-reactive protein

  19. The total synthesis of 3b-hydroxynagilactone F

    NARCIS (Netherlands)

    Reuvers, J.T.A.

    1985-01-01

    The investigations described in this thesis deal with the total synthesis of physiologically active nor- and bisnorditerpenoid dilactones (fig.1).The goal was to design a synthetic route for this class of natural products and its derivatives. From a retrosynthe

  20. Total Synthesis of (±)-7-epi-Nemorosone

    Science.gov (United States)

    Zhang, Qiang; Porco, John A.

    2012-01-01

    A concise total synthesis of (±)-7-epi-nemorosone is reported. Our synthetic approach establishes a viable route to polycyclic polyprenylated acylphloroglucinol natural products (PPAP’s) bearing a C-7 endo prenyl sidechain. Key steps include retro-aldol-vinyl cerium addition to a hydroxy adamantane core scaffold and palladium-mediated deoxygenation. PMID:22449198

  1. Total Synthesis of Three New Dihydrostilbenes from Bulbophllum odoratissimum

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A total synthesis of three new dihydrostilbenes, 1, 2 and 3, which were isolated from Bulbophyllum odoratissimum Lindl. with significant cytotoxicity toward human cancer cell lines,was developed via Horner reaction etc. The natural products 1, 2 and 3 were obtained in 5.8%,6.6% and 5.9%, respectively.

  2. The First Total Synthesis of Triprenylquinone and Hydroquinones

    Institute of Scientific and Technical Information of China (English)

    Chun Hong LI; Xue Song CHEN; Guang Lian ZHOU; Zhi Xiang XIE; Ying LI

    2005-01-01

    First total synthesis of triprenylquinone and hydroquinones, three naturally occurring compound 1, 2 and (±) 3, have been achieved from readily available 2-bromo-5-methyl-1,4-dimethoxybenzene 4 and geranyl bromide. The triprenylquinone and hydroquinones precursor were readily prepared with use of a Julia reaction.

  3. Toward the total synthesis of ent-progesterone

    Czech Academy of Sciences Publication Activity Database

    Kapras, Vojtěch; Jahn, Ullrich

    Praha : Czech Chemical Society, 2014. s. 37. [Liblice 2014. Advances in Organic, Bioorganic and Pharmaceutical Chemistry /49./. 07.11.2014-09.11.2014, Lázně Bělohrad] Institutional support: RVO:61388963 Keywords : ent- steroids * total synthesis * radical cyclization Subject RIV: CC - Organic Chemistry

  4. 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...

  5. Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B.

    Science.gov (United States)

    Feng, Yu; Liu, Jun; Carrasco, Yazmin P; MacMillan, John B; De Brabander, Jef K

    2016-06-01

    We describe the isolation, structure elucidation, and total synthesis of the novel marine natural product rifsaliniketal and the total synthesis of the structurally related variants salinisporamycin and saliniketals A and B. Rifsaliniketal was previously proposed, but not observed, as a diverted metabolite from a biosynthetic precursor to rifamycin S. Decarboxylation of rifamycin provides salinisporamycin, which upon truncation with loss of the naphthoquinone ring leads to saliniketals. Our synthetic strategy hinged upon a Pt(II)-catalyzed cycloisomerization of an alkynediol to set the dioxabicyclo[3.2.1]octane ring system and a fragmentation of an intermediate dihydropyranone to forge a stereochemically defined (E,Z)-dienamide unit. Multiple routes were explored to assemble fragments with high stereocontrol, an exercise that provided additional insights into acyclic stereocontrol during stereochemically complex fragment-assembly processes. The resulting 11-14 step synthesis of saliniketals then enabled us to explore strategies for the synthesis and coupling of highly substituted naphthoquinones or the corresponding naphthalene fragments. Whereas direct coupling with naphthoquinone fragments proved unsuccessful, both amidation and C-N bond formation tactics with the more electron-rich naphthalene congeners provided an efficient means to complete the first total synthesis of rifsaliniketal and salinisporamycin. PMID:27232659

  6. Study on quality control of total alkaloids in Ramulus Uncariae Cum Uncis%钩藤总生物碱有效部位质量控制研究

    Institute of Scientific and Technical Information of China (English)

    蒋海强; 窦月; 周洪雷

    2012-01-01

    Objective:To establish the method for quality control of total alkaloids in Ramulus Uncariae Cum Uncis. Methods;The contents of total alkaloids were determined by acid dye colorimetry,HPLC was used to measure the contents of rhynchophylline and fingerprint of total alkaloids in Ramulus Uncariae Cum Uncis. Results:The contents of total alkaloids were higher than 50%,the linear range of rhynchopHylline was 5.75-92 μg/mL,the average recovery was 98.82%. The chemical composition of different batches total alkaloids in Ramulus Uncariae Cum Uncis was difference by fingerprint similarity evaluation. Conclution:The method can be used for quality control of total alkaloids in Ramulus Uncariae Cum Uncis.%目的:建立钩藤总生物碱有效部位质量控制方法.方法:采用酸性染料染色法测定钩藤总生物碱的含量,采用高效液相色谱法测定有效部位中钩藤碱的含量,采用高效液相色谱法建立钩藤总生物碱有效部位的指纹图谱.结果:钩藤总生物碱的含量均在50%以上,钩藤碱在5.75~ 92 μg/mL之间线性关系良好,平均回收率为98.82%,通过指纹图谱相似度评价,不同批次的钩藤总生物碱有效部位的化学成分存在差异.结论:本研究建立的质量控制方法可有效控制钩藤总生物碱有效部位的质量.

  7. Extraction of Total Alkaloids from Corydalis saxicola Bunting by Enzymatic Method%酶法提取岩黄连总生物碱的研究

    Institute of Scientific and Technical Information of China (English)

    李倩霞; 赵青; 蒋林; 杨得坡; 陈建萍; 王冬梅

    2009-01-01

    目的 研究植物提取酶在提取岩黄连总生物碱中的应用.方法 岩黄连药材经酶处理后用乙醇回流提取总生物碱,通过正交实验优化酶处理工艺参数.结果 酶解反应的最佳工艺条件为:温度45℃、酶反应时间16 h、pH 5.0、酶用量0.9%.结论 药材经酶处理后再用乙醇回流提取,对总生物碱的提取率比传统的直接乙醇回流提取法的提取率提高约24%,适用于岩黄连总生物碱的辅助提取.%Objection To study the extraction of total alkaloids from Corydalis saxicola Bunting by enzymatic method. Methods C. saxicola was treated by enzyme before refluxed with 60% ethanol aqueous solution, and the parameters of enzymatic hydrolysis was optimized by an orthogonai experiment. Results The optimum enzymatic hydrolysis conditions were determined as follows: temperature was 45℃ , reaction time was 16 h, pH value of the buffer solution was 5.0 and 0.9% of enzyme amount. Conclusion The yield of total alkaloids extracted from C. saxicola with pretreatment by enzymatic hydrolysis increased about 24% than that of without enzymatic hydrolysis pretreatment. Enzymatic hydrolysis could be applied as an assistant for the extraction of total alkoids from C. saxicola.

  8. The Catalytic Enantioselective Total Synthesis of (+)‐Liphagal

    DEFF Research Database (Denmark)

    Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.;

    2011-01-01

    Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwaveassisted metal...... establish the trans homodecalin system found in the natural product...... catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to...

  9. Catalytic Asymmetric Total Synthesis of Hedyosumins A, B, and C.

    Science.gov (United States)

    Sun, Wang-Bin; Wang, Xuan; Sun, Bing-Feng; Zou, Jian-Ping; Lin, Guo-Qiang

    2016-03-18

    The first and asymmetric total synthesis of hedyosumins A, B, and C was accomplished in 13-14 steps from simple starting materials. The essential tools that allow us to access the tetracyclic skeleton include an organocatalytic [4 + 3] cycloaddition reaction, an intramolecular aldol condensation, and an intramolecular carboxymercuration/demercuration enabled lactonization. A CBS-catalyzed asymmetric reduction was employed to boost the ee of the synthetic natural products to an excellent level. This synthesis established the absolute configurations of hedyosumins A, B, and C. PMID:26925758

  10. Stereoselective synthesis of epoxides and diepoxides. Applications in total synthesis of natural products and analogues

    OpenAIRE

    García Ruiz, María Cristina

    2014-01-01

    The present work is on the total synthesis of the natural compounds and/or analogues of Bengamides, Gummiferol and Depudecin. The target molecules, selected in virtue of their prominent biological activity as antibiotic and antitumor agents are featured by the presence of one or two epoxide groups and were synthesized by application of a novel methodology of asymmetric epoxidation based on the use of a new class of chiral sulfur ylides. The aim of every total synthesis discussed in this thesi...

  11. Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes.

    Science.gov (United States)

    Yuan, Changxia; Jin, Yehua; Wilde, Nathan C; Baran, Phil S

    2016-07-11

    In the realm of natural product chemistry, few isolates have risen to the level of fame justifiably accorded to Taxol (1) and its chemical siblings. This report describes the most concise route to date for accessing the highly oxidized members of this family. As representative members of taxanes containing five oxygen atoms, decinnamoyltaxinine E (2) and taxabaccatin III (3), have succumbed to enantioselective total synthesis for the first time in only 18 steps from a simple olefin starting material. The strategy holistically mimics nature's approach (two-phase synthesis) and features a carefully choreographed sequence of stereoselective oxidations and a remarkable redox-isomerization to set the key trans-diol present in 2 and 3. This work lays the critical groundwork necessary to access even higher oxidized taxanes such as 1 in a more practical fashion, thus empowering a medicinal chemistry campaign that is not wedded to semi-synthesis. PMID:27240325

  12. Vinca Alkaloids

    Directory of Open Access Journals (Sweden)

    Maryam Moudi

    2013-01-01

    Full Text Available Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL, vinorelbine (VRL, vincristine (VCR and vindesine (VDS. VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard.

  13. Investigation of free amino acid, total phenolics, antioxidant activity and purine alkaloids to assess the health properties of non-Camellia tea

    Directory of Open Access Journals (Sweden)

    Wu Bi

    2016-03-01

    Full Text Available To find novel functional beverages from folk teas, 33 species of frequently used non-Camellia tea (plants other than Camellia were collected and compared with Camellia tea (green tea, pu-erh tea and black tea for the first time. Data are reported here on the quantities of 20 free amino acids (FAAs and three purine alkaloids (measured by UHPLC, total polyphenols (measured by Folin-Ciocalteu assay, and antioxidant activity (DPPH. The total amounts of FAAs in non-Camellia tea (0.62–18.99 mg/g are generally less than that of Camellia tea (16.55–24.99 mg/g. However, for certain FAAs, the quantities were much higher in some non-Camellia teas, such as γ-aminobutyric acid in teas from Ampelopsis grossedentata, Isodon serra and Hibiscus sabdariffa. Interestingly, theanine was detected in tea from Potentilla fruticosa (1.16±0.81 mg/g. Furthermore, the content of polyphenols in teas from A. grossedentata, Acer tataricum subsp. ginnala are significantly higher than those from Camellia tea; teas from I. serra, Pistacia chinensis and A. tataricum subsp. ginnala have remarkable antioxidant activities similar to the activities from green tea (44.23 μg/mL. Purine alkaloids (caffeine, theobromine and theophylline were not detected in non-Camellia teas. The investigation suggest some non-Camellia teas may be great functional natural products with potential for prevention of chronic diseases and aging, by providing with abundant polyphenols, antioxidants and specific FAAs.

  14. Investigation of free amino acid, total phenolics, antioxidant activity and purine alkaloids to assess the health properties of non-Camellia tea.

    Science.gov (United States)

    Bi, Wu; He, Chunnian; Ma, Yunyun; Shen, Jie; Zhang, Linghua Harris; Peng, Yong; Xiao, Peigen

    2016-03-01

    To find novel functional beverages from folk teas, 33 species of frequently used non-Camellia tea (plants other than Camellia) were collected and compared with Camellia tea (green tea, pu-erh tea and black tea) for the first time. Data are reported here on the quantities of 20 free amino acids (FAAs) and three purine alkaloids (measured by UHPLC), total polyphenols (measured by Folin-Ciocalteu assay), and antioxidant activity (DPPH). The total amounts of FAAs in non-Camellia tea (0.62-18.99 mg/g) are generally less than that of Camellia tea (16.55-24.99 mg/g). However, for certain FAAs, the quantities were much higher in some non-Camellia teas, such as γ-aminobutyric acid in teas from Ampelopsis grossedentata, Isodon serra and Hibiscus sabdariffa. Interestingly, theanine was detected in tea from Potentilla fruticosa (1.16±0.81 mg/g). Furthermore, the content of polyphenols in teas from A. grossedentata, Acer tataricum subsp. ginnala are significantly higher than those from Camellia tea; teas from I. serra, Pistacia chinensis and A. tataricum subsp. ginnala have remarkable antioxidant activities similar to the activities from green tea (44.23 μg/mL). Purine alkaloids (caffeine, theobromine and theophylline) were not detected in non-Camellia teas. The investigation suggest some non-Camellia teas may be great functional natural products with potential for prevention of chronic diseases and aging, by providing with abundant polyphenols, antioxidants and specific FAAs. PMID:27006902

  15. [Synthesis of indole compounds using multifunctional synthons].

    Science.gov (United States)

    Abe, Takumi

    2013-01-01

    This review describes a synthesis of indole compounds using multifunctional synthons. The multifunctional synthons, trienes and gramines, were respectively synthesized using Pd-catalyzed tandem cyclization/cross-coupling reaction of indolylborate with vinyl bromide, and reaction of indolylcuprate with iminium chloride. As an application of the multifunctional synthons to the indole alkaloids synthesis, we accomplished the total synthesis of ellipticine, 9-methoxyellipticine, 9-hydroxyellipticine, tetrahydroellipticine, μ-alkaloid B, μ-alkaloid D, calothrixin A, calothrixin B, tubifoline, and yuehchukene. We have also developed 6π-electrocyclization of hexatrienes catalyzed by Cu(I) trifluoromethanesulfonate toluene complexe, which is unprecedented. PMID:23292026

  16. Enantioselective synthesis of 1,2,4-triazolines catalyzed by a cinchona alkaloid-derived organocatalyst.

    Science.gov (United States)

    Shao, Qian; Chen, Jiean; Tu, Meihua; Piotrowski, David W; Huang, Yong

    2013-12-01

    An enantioselective organocatalytic process for the one-step synthesis of poly-substituted 1,2,4-triazolines is reported. The heterocycle formation is believed to go through a step-wise mechanism of nucleophilic addition of an azlactone to an azodicarboxylate in the presence of an organic base catalyst, followed by a TMSCHN2 mediated heterocyclization. Both theoretical calculations and experimental evidence suggest the pre-organization of the transition state for the chirality determining step via a unique 7-membered intramolecular hydrogen bonding. PMID:24145477

  17. Total synthesis and development of bioactive natural products

    OpenAIRE

    TATSUTA, Kuniaki

    2008-01-01

    The first total synthesis and development of a variety of bioactive natural products have been accomplished by using carbohydrates as a chiral source. In addition, practically useful intermediates have been created, analogs of natural products have been prepared, their structure-activity relationships studied, and the large-scale preparations of medicinally useful compounds established. The key target molecules have been the “Big Four” antibiotics (macrolides, aminoglycosides, β-lactams and t...

  18. Total synthesis of an oxepine natural product, (±)-janoxepin.

    Science.gov (United States)

    Doveston, Richard G; Steendam, René; Jones, Stuart; Taylor, Richard J K

    2012-02-17

    The total synthesis of (±)-janoxepin, a novel antiplasmodial d-leucine derived oxepine-pyrimidinone-ketopiperazine isolated from the fungus Aspergillus janus, is described. The cornerstones of the synthetic route are pyrimidinone preparation, ring-closing metathesis, aldol introduction of the enamide, and dihydro-oxepine elaboration. This synthetic route proved very efficient for the formation of a number of janoxepin analogues, including dihydro-janoxepin and tetrahydro-janoxepin. PMID:22288766

  19. First total synthesis of two nematicidal prenylated flavanones

    Institute of Scientific and Technical Information of China (English)

    Jin Hui Yang; Shi Zhi Jiang; Yan Min Zhao; Yun Feng Li; Cong Bin Ji; Wan Yi Liu

    2009-01-01

    The total synthesis of(±)-8-(3-methylbut-2-enyl)-2-phenyl-2,3-dihydrochromen-4-one and(±)-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one was first achieved through C-prenylation,protection of phenolic hydroxyl group,aldol condensation,cyclization and deprotection starting from cheap benzaldehyde,4-hydroxybenzaldehyde and 2-hydroxyacetophenone,with total yield of 20 and 16.3%.All structures of new compounds were confirmed by IR,1H NMR and MS.

  20. A Highly Convergent Total Synthesis of Leustroducsin B.

    Science.gov (United States)

    Trost, Barry M; Biannic, Berenger; Brindle, Cheyenne S; O'Keefe, B Michael; Hunter, Thomas J; Ngai, Ming-Yu

    2015-09-16

    Leustroducsin B exhibits a large variety of biological activities and unique structural features. An efficient and highly convergent total synthesis of Leustroducsin B was achieved in 17 longest linear and 39 total steps by disconnecting the molecule into three fragments having similar levels of complexity. These pieces were connected via a highly efficient chelate-controlled addition of a vinyl zincate to an α-hydroxy ketone and a silicon-mediated cross-coupling. The stereochemistry of the central and western fragments was set catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol reaction and a palladium-catalyzed asymmetric allylic alkylation. PMID:26313159

  1. Synthesis of derivatives of tetronic acid and pulvinic acid. Total synthesis of norbadione A

    International Nuclear Information System (INIS)

    When vegetables like mushrooms are contaminated by radioactive caesium 137, this radioactive caesium is associated to norbadione A, a natural pigment present in two mushroom species and which can be used as a caesium decorporation agent or maybe as protection agent against ionizing radiations. Within this perspective, this research report describes the biosynthesis and the structure and properties of the norbadione A and of pulvinic acids (physicochemical properties, anti-oxidizing properties). Then, it presents the various tetronic acids (3-acyl-, 3-alkyl-, 3-alkoxy-, 3-aryl-tetronic acids and non 3-substituted tetronic acids), their synthesis path as they are described in the literature, and presents a new synthesis approach using a tandem reaction (with different esters or hydroxy esters) and the synthesis of tetronic acids. The author also proposes a new synthesis way for methyl pulvinates, and finally reports the work on the development of a total synthesis of the norbadione A

  2. Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A

    OpenAIRE

    Chen, Jiehao; Forsyth, Craig J.

    2004-01-01

    A total synthesis of apratoxin A was developed. Apratoxin A, isolated from Lyngbya spp. cyanobacteria, is representative of a growing class of marine cyanobacterial cyclodepsipeptides wherein discrete polypeptide and polyketide domains are merged by ester and amide or amide-derived linkages. In the apratoxins, the N terminus of the peptide domain [(Pro)-(N-Me-Ile)-(N-Me-ala)-(O-Me-Tyr)-(moCys)] is a modified vinylogous cysteine that is joined to a novel ketide [3,7-dihydroxy-2,5,8,8-tetrameth...

  3. Total Synthesis and Biological Assessment of Mandelalide A.

    Science.gov (United States)

    Brütsch, Tobias Michael; Bucher, Pascal; Altmann, Karl-Heinz

    2016-01-22

    A new convergent total synthesis of the marine macrolide mandelalide A (1) has been developed that is based on macrocyclic ring closure by a Shiina-type macrolactonization and the construction of the requisite precursor seco acid by a highly efficient Sonogashira cross-coupling reaction between two fragments of comparable complexity. Key steps in the elaboration of the acid building block were the enantioselective, catalytic addition of a protected acetylene to crotonaldehyde and the construction of the tetrahydropyran unit that is embedded in the macrocycle by means of an acid-catalyzed Prins reaction. The synthesis of the alcohol fragment features the formation of the trisubstituted tetrahydrofuran ring through an acetal cleavage/epoxide opening cascade reaction and a rarely used radical alkynylation of a primary alkyl iodide. Intriguingly, the dihydroxylation of a terminal double bond as part of the synthesis of this building block gave the same major product for both the α- and β-AD-mix reagents, albeit with moderate or low selectivity. Synthetic mandelalide A (1) was a potent proliferation inhibitor of A549, HT460, and H1299 human lung cancer cells in vitro, but not of SK-N-SH neuroblastoma cells. However, in no case did we observe complete cell kill even at the highest compound concentration tested (5 μm). PMID:26639765

  4. Cobalt-catalyzed diastereoselective synthesis of C-furanosides. Total synthesis of (-)-isoaltholactone.

    Science.gov (United States)

    Nicolas, Lionel; Izquierdo, Eva; Angibaud, Patrick; Stansfield, Ian; Meerpoel, Lieven; Reymond, Sébastien; Cossy, Janine

    2013-12-01

    An array of C-aryl and C-vinyl furanosides were prepared in good yields and diastereoselectivities from C-halogeno furanosides either with aryl Grignard or with vinyl Grignard using the convenient Co(acac)3/TMEDA catalytic system. This method is illustrated by the total synthesis of the (-)-isoaltholactone. PMID:24127819

  5. 离子交换树脂对钩藤总生物碱的纯化工艺%Purification Technology of Total Alkaloids from Uncaria rhynchophylla by Ion-Exchange Resin

    Institute of Scientific and Technical Information of China (English)

    窦月; 周洪雷; 齐冬梅; 李运伦; 陈凯

    2012-01-01

    Objective: To establish purification technology of total alkaloids from Uncaria rhynchophylla with cation-exchange resin. Method: Total alkaloids from U. Rhynchophylla was selected as indicator, and investigated separation technology conditions of total alkaloids from U. Rhynchophylla by ion-exchange resin. Result:Seven hundred and thirty-two cation-exchange resin was chosen,flow rate of sample was 1 mL·min-1 of flow rate,then eluted with 10 BV water and 6 BV 80% ethanol,finally eluted with 1% aqueous ammonia 80% ethanol, the content of total alkaloids from U. Rhynchophylla was up to 50% . Conclusion: This technology was simply, the content of total alkali was high, suitable for industrial production.%目的:建立阳离子交换树脂纯化钩藤总生物碱的工艺.方法:以钩藤总生物碱为研究指标,考察离子交换树脂分离钩藤总生物碱的工艺条件.结果:选择732型阳离子交换树脂,以1 mL· min -1的流速上样,分别用10 BV水,6 BV 80%乙醇洗脱除杂,最后选用1%氨性80%乙醇洗脱得到钩藤总生物碱,含量达到50%.结论:该方法工艺较简单,总碱含量较高,适合工业化生产.

  6. 半夏与钩藤生物总碱联合抗惊厥作用及毒性反应的定量评价%Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice

    Institute of Scientific and Technical Information of China (English)

    张密; 李禄金; 吕映华; 郑青山

    2010-01-01

    目的:利用已发表的半夏生物总碱(pinellia total alkaloid,PTA)与钩藤生物总碱(uncaria total alkaloid,UTA)联合抗惊厥和毒性作用数据,全面定量评价其相互作用和组方合理性.方法:采用等效图法(isobologram)和计算机模拟技术,定量评价不同强度(0%~99%)有效剂量(ED)和致死剂量(LD)的相互作用,并综合计算其获益指数(BI)和治疗指数(TI).结果:3个配比(PTA:UTA=1:4,1:1,4:1)有协同作用趋势.由于最高剂量的有效率均低于70%,给参数计算和研究结论带来不确定性.PTA和UTA按4:1联用的毒性呈现拮抗作用,其它2个配比毒性拮抗作用不明确.基于ED和LD参数的综合分析,3个配比的BI均大于1,其中4:1配比的减毒增效作用明确,TI增大.结论:PTA和UTA按4:1给药后安全性和有效性提高,呈现配伍优势.从方法学角度,本研究可对同类实验的设计和分析提供参考.

  7. Total synthesis of cytotoxic metabolite ( ± )-desmethyldiaportinol from Ampelomyces sp.

    Science.gov (United States)

    Saeed, Aamer; Qasim, Muhammad

    2014-01-01

    A concise total synthesis of ( ± )-desmethyldiaportinol isolated from Ampelomyces sp. is described. Microwave-assisted cyclocondensation of 3,5-dimethoxyhomopthalic acid with 3,4-dibromobutanoyl chloride afforded the 3-(2,3-dibromopropyl)-6, 8-dimethoxyisocoumarin in 2-3 min as the pivotal step. The 3,4-dibromobutanoyl chloride was itself synthesised from 3-butenoic acid via bromination in carbon tetrachloride at room temperature to yield 3,4-dibromobutanoic acid followed by reaction with thionyl chloride. The replacement of bromo- by hydroxyl substituent was achieved under mild conditions involving the refluxing in a mixture of acetone and water to provide ( ± )-3-(2,3-dihydroxypropyl)-6,8-dimethoxyisocoumarin which on complete demethylation furnished the title natural product. PMID:24303787

  8. Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A.

    Science.gov (United States)

    Ronson, Thomas O; Burns, Michael J; Voelkel, Martin H H; Evans, Kieren J; Lynam, Jason M; Taylor, Richard J K; Fairlamb, Ian J S

    2015-12-21

    The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including Au(I)-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products. PMID:26568186

  9. Catalytic asymmetric total synthesis of (-)-galanthamine and (-)-lycoramine.

    Science.gov (United States)

    Li, Lei; Yang, Qiao; Wang, Yuan; Jia, Yanxing

    2015-05-18

    The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)-lycoramine (2) have been achieved by using a conceptually new strategy featuring two metal-catalyzed reactions as the key steps. A new method for the construction of 3,4-fused benzofurans has been developed through a palladium-catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric synthesis of 1 and 2, a Sc(III)/N,N'-dioxide complex was used to catalyze the enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center. PMID:25847447

  10. Studies towards the total synthesis of novel marine diterpene havellockate. Construction of the tetracyclic core

    OpenAIRE

    Mehta, Goverdhan; Kumaran, Senthil R

    2001-01-01

    The synthesis of the tetracyclic core present in the novel marine diterpenoid havellockate 1 has been accomplished from the readily available endo-dicyclopentadienone-10-ethylene ketal 3 as a prelude to the projected total synthesis of the natural product.

  11. Total synthesis and isolation of citrinalin and cyclopiamine congeners

    Science.gov (United States)

    Romminger, Stelamar; Pimenta, Eli. F.; Romney, David K.; Lodewyk, Michael W.; Williams, David E.; Andersen, Raymond J.; Miller, Scott J.; Tantillo, Dean J.; Berlinck, Roberto G. S.; Sarpong, Richmond

    2014-01-01

    It is said that carbon, the most abundant element in organic matter, supplies life’s quantity, whereas nitrogen supplies its quality. It is therefore unsurprising that many natural products that contain basic nitrogens (alkaloids) are coveted for their benefit to human health. However, nitrogen is known to mire many chemical syntheses because of its basicity and susceptibility to oxidation. This challenge may be heightened by the presence of more than one nitrogen atom in a targeted complex alkaloid, but can be met by the selective introduction and removal of functional groups that mitigate basicity, as highlighted herein with the first chemical syntheses of citrinalin B and cyclopiamine B. The chemical connections that have been realized as a result of these syntheses, in addition to the isolation of both 17-hydroxycitrinalin B and citrinalin C through 13C feeding studies, supports the existence of a common bicyclo[2.2.2]diazaoctane containing biogenetic precursor to these compounds as has been proposed previously. PMID:24828190

  12. Direct Synthesis of Protoberberine Alkaloids by Rh-Catalyzed C-H Bond Activation as the Key Step.

    Science.gov (United States)

    Jayakumar, Jayachandran; Cheng, Chien-Hong

    2016-01-26

    A one-pot reaction of substituted benzaldehydes with alkyne-amines by a Rh-catalyzed C-H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β-unsaturated aldehydes and amino-alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O2 as the oxidant. PMID:26689172

  13. Click-based synthesis of bromotyrosine alkaloid analogs as potential anti-biofilm leads for SAR studies.

    Science.gov (United States)

    Andjouh, S; Blache, Y

    2015-12-15

    A library of triazole-based analogs of bromotyramine alkaloids such as verongamines, hemibastadins, pseudoceramine D and clavatidine E was designed in order to identify promising leads that may help in the control of bacterial biofilms. Twenty-three compounds were screened for their biofilm inhibitory activity against three strains of Gram-negative bacteria. SAR studies revealed that hemibastadins analogs were the most active compounds which act as inhibitors of biofilm development (EC50 8.8-29μM) without effect on bacterial growth even at high concentrations (100μM). PMID:26564265

  14. Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (-)-Bisezakyne A.

    Science.gov (United States)

    Shin, Iljin; Lee, Dongjoo; Kim, Hyoungsu

    2016-09-01

    The first asymmetric total synthesis and subsequent structure revision of (-)-bisezakyne A, a Laurencia C15 acetogenin from Alpysia oculifera, has been accomplished. Our substrate-controlled synthesis of this oxolane natural product features a highly stereoselective "protecting-group-dependent" intramolecular amide enolate alkylation strategy for the synthesis of the key 9,10-trans-9,12-cis-10-hydroxytetrahydrofuran intermediate through "nonchelate" control. In addition, our synthesis determined the absolute configuration of the halogenated marine natural product. PMID:27551943

  15. The CP molecule labyrinth: a paradigm of how endeavors in total synthesis lead to discoveries and inventions in organic synthesis.

    Science.gov (United States)

    Nicolaou, K C; Baran, Phil S

    2002-08-01

    Imagine an artist carving a sculpture from a marble slab and finding gold nuggets in the process. This thought is not a far-fetched description of the work of a synthetic chemist pursuing the total synthesis of a natural product. At the end of the day, he or she will be judged by the artistry of the final work and the weight of the gold discovered in the process. However, as colorful as this description of total synthesis may be, it does not entirely capture the essence of the endeavor, for there is much more to be told, especially with regard to the contrast of frustrating failures and exhilarating moments of discovery. To fully appreciate the often Herculean nature of the task and the rewards that accompany it, one must sense the details of the enterprise behind the scenes. A more vivid description of total synthesis as a struggle against a tough opponent is perhaps appropriate to dramatize these elements of the experience. In this article we describe one such endeavor of total synthesis which, in addition to reaching the target molecule, resulted in a wealth of new synthetic strategies and technologies for chemical synthesis. The total synthesis of the CP molecules is compared to Theseus' most celebrated athlos (Greek for exploit, accomplishment): the conquest of the dreaded Minotaur, which he accomplished through brilliance, skill, and bravery having traversed the famous labyrinth with the help of Ariadne. This story from Greek mythology comes alive in modern synthetic expeditions toward natural products as exemplified by the total synthesis of the CP molecules which serve as a paradigm for modern total synthesis endeavors, where the objectives are discovery and invention in the broader sense of organic synthesis. PMID:12203464

  16. Studies toward the synthesis of (-)-anisomycin. The total synthesis of (-)-2-epi-anisomycin

    OpenAIRE

    Brann, Paul John

    2013-01-01

    Exploitation of the asymmetric electron density at the crown of the oxazolidinone [221] allowed for high diastereofacial selectivity when converting the olefin to an epoxide. Regiocontrolled fragmentation of the epoxide enabled us to introduce the three essential stereocentres of the target alkaloid (-)-anisomycin [1] both contiguously and with the correct geometry. Installation of the remaining aromatic appendage allowed us to complete the molecular skeleton of the natural product; however, ...

  17. Aza-Quaternary Scaffolds from Selective Bond Cleavage of Bridgehead-Substituted 7-Azabicyclo[2.2.1]heptane: Total Synthesis of (+)-Cylindricines C-E and (-)-Lepadiformine A.

    Science.gov (United States)

    Pandey, Ganesh; Janakiram, Vaitla

    2015-09-01

    A novel bridgehead-substituted aza-bicyclic framework has been designed and developed in both enantiomeric forms through an asymmetric desymmetrization reaction. Strategic exploitation of the ring strain in the aza-bicyclic framework has been utilized for the construction of the chiral aza-quaterenary scaffolds by selective bond fragmentation processes. Furthermore, a strategically designed precursor is employed for selective bond cleavage to initiate a cascade rearrangement for the total synthesis of the 1-azaspirotricyclic marine alkaloids (+)-cylindricines C, D, and E, as well as (-)-lepadiformine A. An oxidation/retro-aldol/aza-Michael sequence generated three new chiral centers with the required configuration in one pot. PMID:26220441

  18. Total Synthesis of the Proposed Structure of the Macrolide Queenslandonand Towards the Total Synthesis of Natural Products Leiodermatolide and (–)-Englerin A

    OpenAIRE

    Navickas, Vaidotas

    2011-01-01

    The dissertation consists of three parts. The first part deals with the total synthesis of macrolide queenslandon. Key steps in the synthesis were a cross metathesis reaction to construct the aliphatic fragment and a Mitsunobu macrolactonization to give a macrolactone. All chiral centers were established from D-(+)-ribose. The proposed structure of the macrolide queenslandon has been reached and it was proved that the postulated structure was proposed incorrectly. The second part describ...

  19. Alkaloids in the pharmaceutical industry: Structure, isolation and application

    Directory of Open Access Journals (Sweden)

    Nikolić Milan

    2003-01-01

    Full Text Available By the end of the 18th and the beginning of the 19th century a new era began in medicine, pharmaceutics and chemistry that was strongly connected with alkaloids and alkaloid drugs. Even before that it was known that certain drugs administered in limited doses were medicines, and toxic if taken in larger doses (opium, coke leaves, belladonna roots, monkshood tubers crocus or hemlock seeds. However, the identification, isolation and structural characterization of the active ingredients of the alkaloid drugs was only possible in the mid 20th century by the use of modern extraction equipment and instrumental methods (NMR, X-ray diffraction and others.In spite of continuing use over a long time, there is still great interest in investigating new drugs, potential raw materials for the pharmaceutical industry, as well as the more detailed investigation and definition of bio-active components and the indication of their activity range, and the partial synthesis of new alkaloid molecules based on natural alkaloids. The scope of these investigations, especially in the field of semi-synthesis is to make better use of the bio-active ingredients of alkaloid drugs, i.e. to improve the pharmacological effect (stronger and prolonged effect of the medicine, decreased toxicity and side effects, or to extend or change the applications. A combined classification of alkaloids was used, based on the chemical structure and origin, i.e. the source of their isolation to study alkaloid structure. For practical reasons, the following classification of alkaloids was used: ergot alkaloids, poppy alkaloids, tropanic alkaloids purine derivative alkaloids, carbon-cyclic alkaloids, and other alkaloids. The second part of this report presents a table of general procedures for alkaloid isolation from plant drugs (extraction by water non-miscible solvents, extraction by water-miscible solvents and extraction by diluted acid solutions. Also, methods for obtaining chelidonine and

  20. Total synthesis and evaluation of [18F]MHMZ

    DEFF Research Database (Denmark)

    Herth, Matthias M; Debus, Fabian; Piel, Markus;

    2008-01-01

    Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall...... radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in...

  1. Enantioselective total synthesis of (R)-(−)-complanine

    OpenAIRE

    Kamanos, Krystal A D; Jonathan M. Withey

    2012-01-01

    A route is described for the enantioselective synthesis of (R)-(−)-complanine, a marine natural product isolated from Eurythoe complanata, and known to be a causative agent in inflammation. An organocatalytic, asymmetric oxyamination of a homoconjugated all-Z-dienal intermediate provides versatile and efficient access to the natural product.

  2. Enantioselective total synthesis of (R)-(−)-complanine

    OpenAIRE

    Kamanos, Krystal A D; Jonathan M. Withey

    2012-01-01

    A route is described for the enantioselective synthesis of (R)-(−)-complanine, a marine natural product isolated from Eurythoe complanata, and known to be a causative agent in inflammation. An organocatalytic, asymmetric oxyamination of a homoconjugated all-Z-dienal intermediate provides versatile and efficient access to the natural product.

  3. The total chemical synthesis of polymer/graphene nanocomposite films.

    Science.gov (United States)

    Salvatierra, Rodrigo V; Cava, Carlos E; Roman, Lucimara S; Oliveira, Marcela M; Zarbin, Aldo J G

    2016-01-28

    A versatile and room temperature synthesis of thin films of polymer/graphene is reported. Drastically differing from other methods, not only the polymer but also the graphene are completely built from their simplest monomers (thiophene and benzene) in a one-pot polymerization reaction at a liquid-liquid interface. The materials were characterized and electronic properties are presented. PMID:26658554

  4. 荷叶总生物碱降脂减肥作用的体内外试验%Effect of total alkaloids from lotus leaves on body mass and lipid regulation in vivo and in vitro .

    Institute of Scientific and Technical Information of China (English)

    范婷婷; 法鲁克; 方芳; 蒋益虹

    2013-01-01

    components . In modern research , scientists found that alkaloids were one of the main bioactive ingredients in them , helping lowing the serum lipid level and controlling body mass . Thus , this study aims to investigate the effect of lotus leaf total alkaloids on the body mass and lipid regulation in in vivo and in vitro experiments , and to find a new potential food additive to prevent effectively obesity from abnormal fat accumulation . Lipid‐lowering efficacy in vivo of lotus leaf total alkaloids was determined by animal experiment . After adapting to the feeding environment for 10 days , 30 experimental rats were randomly divided into six experimental groups according to their serum‐lipid level and body mass , including general diet group ( blank group) , high fat diet with lotus leaf total alkaloid ( high , moderate , low doses) groups , positive drug control group and high fat diet group ( model group) . Except for the general diet group feeding normal diet , the other five groups were fed high fat diet for 40 d to set up the model of hyperlipidemia rats . Then , the contents of TC ( total cholesterol) , TG ( triglyceride) , LDL‐C ( low density lipoprotein‐cholesterol) , HDL‐C ( high density lipoprotein‐cholesterol) , the levels of AST ( aspartate aminotransferase) and ALT ( alanine aminotransferase) in serum were assayed in hyperlipidemia rats which had been fed lotus leaf total alkaloids of 20 , 40 , 80 mg/( kg·d) and positive drug of 10 mg/( kg·d) simvastatin for another 40 days , respectively . In addition , the body mass and liver mass , body length , tail length were measured . Lipid‐lowering efficacy in vitro of lotus leaf total alkaloids was determined by measuring the inhibitory activity against pancrelipase by monitoring the hydrolysis of pNP‐b , which released the yellow chromogen p‐nitrophenol , and the buffer solution was adjusted to the condition of 37 ℃ , pH=7 .4 . The results showed that , compared with high fat diet group

  5. Expedient access to enantiopure cyclopentanic natural products: total synthesis of (-)-cyclonerodiol.

    Science.gov (United States)

    Pérez Morales, Carmen; Mar Herrador, M; Quílez del Moral, José F; Barrero, Alejandro F

    2015-01-01

    Following the principles of collective total synthesis, a number of natural products sharing an optically pure, multifunctional, cyclopentanic core were synthesized from a common precursor: plinol A (1). This intermediate was efficiently obtained in only four steps from (-)-linalool (2) using as the key step a Ti(III)-mediated diastereoselective radical cyclization. The feasibility of this approach was confirmed with the expedient enantiospecific synthesis of cyclonerodiol (3), and the formal synthesis of chocol G (4) and piperitone (5). PMID:25920207

  6. Total Synthesis of Nominal Cyclocinamide B and Investigation into the Identity of the Cyclocinamides

    OpenAIRE

    Curzon, Stephanie S.; Garcia, Jessica M.; Konopelski, Joseph P.

    2014-01-01

    The total synthesis of nominal cyclocinamide B, a cyclic peptide marine natural product, is reported together with an isomer of nominal cyclocinamide A. Initial attempts at the synthesis of the title compounds by inclusion of a turn inducer failed. However, direct synthesis succeeded in formation of the 14-membered cyclic peptide structure. Comparison of the data from all synthetic cyclocinamide A and B compounds with those of the natural products leads to the conclusion that the two natural ...

  7. Progress Toward the Total Synthesis of Vinigrol and Hibarimicin B

    OpenAIRE

    Milgram, Benjamin Charles

    2013-01-01

    Vinigrol is a structurally unique diterpenoid natural product featuring a tricyclo[4.4.4.0.4a,8a]tetradecene carbon skeleton containing eight contiguous stereocenters and a challenging oxygenation pattern. Vinigrol has been demonstrated to possess a wide array of biological activities including tumor necrosis factor (TNF) antagonism, antihypertensive activity, and platelet aggregation inhibitory activity. Our first-generation plan for the synthesis of vinigrol utilized a cascade reaction sequ...

  8. A carbohydrate approach for the formal total synthesis of (−-aspergillide C

    Directory of Open Access Journals (Sweden)

    Pabbaraja Srihari

    2014-12-01

    Full Text Available An enantioselective formal total synthesis of aspergillide C is accomplished using commercially available tri-O-acetyl-D-galactal employing a Ferrier-type C-glycosylation, utilizing a Trost hydrosilylation and protodesilylation as key reactions.

  9. Total synthesis and allelopathic activity of cytosporones A-C

    Energy Technology Data Exchange (ETDEWEB)

    Zamberlam, Charles E.M.; Meza, Alisson; Lima, Denis P. de; Beatriz, Adilson [Centro de Ciencias Exatas e Tecnologia, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Leite, Carla Braga; Marques, Maria Rita [Centro de Ciencias Biologicas e da Saude, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil)

    2012-07-01

    The search for efficient, environmentally friendly herbicides has been the focus of numerous studies on the organic synthesis of compounds isolated from natural sources. Cytosporones, which are phenolic lipids isolated from fungi, exhibit noteworthy biological properties. This paper reports the preparation of cytosporones A-C from the same starting material through a short synthetic route, with good yields. All compounds were tested for allelopathic activity on lettuce (Lactuca sativa L) seeds. Cytosporone A and its methylated precursor showed remarkable allelopathic activity, inhibiting seed germination and plantule growth. (author)

  10. Total synthesis and allelopathic activity of cytosporones A-C

    International Nuclear Information System (INIS)

    The search for efficient, environmentally friendly herbicides has been the focus of numerous studies on the organic synthesis of compounds isolated from natural sources. Cytosporones, which are phenolic lipids isolated from fungi, exhibit noteworthy biological properties. This paper reports the preparation of cytosporones A-C from the same starting material through a short synthetic route, with good yields. All compounds were tested for allelopathic activity on lettuce (Lactuca sativa L) seeds. Cytosporone A and its methylated precursor showed remarkable allelopathic activity, inhibiting seed germination and plantule growth. (author)

  11. Total Synthesis of Sporolide B and 9-epi-Sporolide B

    OpenAIRE

    Nicolaou, K. C.; Wang, Jianhua; Tang, Yefeng; Botta, Lorenzo

    2010-01-01

    The total synthesis of the structurally unique secondary metabolite sporolide B (1b, Figure 1) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37, Scheme 5; 75, Scheme 11) that underwent exquisite intramolecular [4+2] cycloaddition rea...

  12. One-pot multiple reactions: asymmetric synthesis of 2,6-cis-disubstituted piperidine alkaloids from chiral aziridine.

    Science.gov (United States)

    Yadav, Nagendra Nath; Choi, Jihye; Ha, Hyun-Joon

    2016-07-01

    A divergent, new, and highly stereoselective synthesis of cis-2,6-disubstituted piperidine natural products including isosolenopsins, deoxocassine, and spectaline was achieved from chiral aziridine decorated with appropriate alkyl chains for isosolenopsins or alkynyl groups for deoxocassine and spectaline at C2. The characteristic feature of this synthesis is one-pot sequential reactions under atmospheric hydrogen including the reduction of alkyne (for deoxocassine and spectaline), reductive ring-opening of aziridine, debenzylation, and intramolecular reductive amination in high yields. The prerequisite aziridines were elaborated from commercially available (2S)-hydroxymethylaziridine through oxidation, Wittig olefination, and the Grignard reaction for isosolenopsins or substrate-controlled lithium alkynylate addition for deoxocassine and spectaline. PMID:27189444

  13. Solid substrate mediated changes in ergot alkaloid spectra in solid state fermentation system

    OpenAIRE

    Trejo Hernandez, M.R.; Lonsane, B.K.; Raimbault, Maurice; Roussos, Sevastianos

    1993-01-01

    Use of different solid substrates resulted in minor alterations in total alkaloid production by #Claviceps purpurea$ 1029c in solid state fermentation system but the changes in the spectra of ergot alkaloids were of significantly higher magnitudes. Ergonovine accounted for 93% of the total alkaloid production in wheat grain medium while lysergic acid derivatives and ergonovine comprised of 66% and 32% of total alkaloids in rye grain medium. In contrast, ergonovine, ergotamine, and lysergic ac...

  14. An Enantioselective Approach to the Hetisine Alkaloids. Synthesis of the 3-Methyl-1-aza-tricyclo[5.2.1.03,8]decane Core via Intramolecular Dipolar Cycloaddition

    OpenAIRE

    Peese, Kevin M.; Gin, David Y.

    2005-01-01

    An efficient, enantioselective approach to the hetisine class of the C20-diterpenoid alkaloids is described. The strategy involves an intramolecular oxidopyridinium dipolar cycloaddition as the key transformation, in which simultaneous formation of the C5-C6 and C10-C20 bonds in the 3-methyl-1-aza-tricyclo[5.2.1.03,8]decane core of the hetisine alkaloids is effected.

  15. Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis.

    Science.gov (United States)

    Mann, Stéphane; Carillon, Sophie; Breyne, Olivier; Marquet, Andrée

    2002-01-18

    We describe the first synthesis of amiclenomycin, a natural product that has been found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic properties. Structure 1, with a trans relationship between the ring substituents. had previously been proposed for amiclenomycin on the basis of its 1H NMR spectrum. We have prepared the trans and cis isomers 1 and 2 by unequivocal routes and we conclude that the natural product is in fact the cis isomer 2. The properly substituted cyclohexadienyl rings were constructed first. A cycloaddition reaction between 1,2-di(phenylsulfonyl)ethylene and the N-allyloxycarbonyl diene 13, followed by reductive elimination of the phenylsulfinyl groups, gave the cis isomer 15. To obtain the trans isomer, the O-trimethylsilyl diene was used to give the cis hydroxylated Diels-Alder adduct 33, which was transformed into the corresponding trans amino derivative by means of a Mitsunobu reaction. The L-alpha-amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic hydrolysis with immobilised pronase. PMID:11843156

  16. RIA for indol alkaloids

    International Nuclear Information System (INIS)

    The technique of RIAs for indol alkaloids (ajmaline, ergotamine, ergocristine, ergometrine, and lysergic acid) is described, and applications for this RIA and the RIA for raubasine and serpentine are mentioned. The indol alkaloide RIAs are shown to be suitable both for alkaloid distribution measurements in Catharantus and Rauwolfia plants and C. purpurea sclerotia as well as for the selection of high-efficiency strains and the optimisation of cultures of plant tissues and saprophytic fungi. (orig./MG)

  17. Alkaloids in Marine Algae

    OpenAIRE

    Ekrem Sezik; Aline Percot; Kasım Cemal Güven

    2010-01-01

    This paper presents the alkaloids found in green, brown and red marine algae. Algal chemistry has interested many researchers in order to develop new drugs, as algae include compounds with functional groups which are characteristic from this particular source. Among these compounds, alkaloids present special interest because of their pharmacological activities. Alkaloid chemistry has been widely studied in terrestrial plants, but the number of studies in algae is insignificant. In this review...

  18. Divergent solid-phase synthesis of natural product-inspired bipartite cyclodepsipeptides: total synthesis of seragamide A.

    Science.gov (United States)

    Arndt, Hans-Dieter; Rizzo, Stefano; Nöcker, Christina; Wakchaure, Vijay N; Milroy, Lech-Gustav; Bieker, Vanessa; Calderon, Abram; Tran, Tuyen T N; Brand, Silke; Dehmelt, Leif; Waldmann, Herbert

    2015-03-27

    Macrocyclic natural products (NPs) and analogues thereof often show high affinity, selectivity, and metabolic stability, and methods for the synthesis of NP-like macrocycle collections are of major current interest. We report an efficient solid-phase/cyclorelease method for the synthesis of a collection of macrocyclic depsipeptides with bipartite peptide/polyketide structure inspired by the very potent F-actin stabilizing depsipeptides of the jasplakinolide/geodiamolide class. The method includes the assembly of an acyclic precursor chain on a polymeric carrier, terminated by olefins that constitute complementary fragments of the polyketide section and cyclization by means of a relay-ring-closing metathesis (RRCM). The method was validated in the first total synthesis of the actin-stabilizing cyclodepsipeptide seragamide A and the synthesis of a collection of structurally diverse bipartite depsipeptides. PMID:25694199

  19. Visual identification of alkaloids in some medicinal plants: common alkaloid reagents versus bromocresol green

    Directory of Open Access Journals (Sweden)

    Shamsa F, Esfahani HR, Gamooshi RA

    2008-07-01

    Full Text Available "n Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Background: Alkaloids are a group of nitrogenous compounds with potential effects on the physiological behavior of human and animals. Some of these compounds are considered important drugs in modern medicine, such as atropine and morphine. Plants are considered the most important source of alkaloids. Therefore, investigating the presence of alkaloids in different plants is very important. Usually, alkaloids in plants are identified by methods such as those of Dragendorf, Wagner and Meyer, among others, which require milligrams of alkaloids for identification. In the present study, a fast and sensitive procedure for detecting of alkaloids in plants is presented.   "n"nMethods: Twelve dried plants samples were investigated for the presence alkaloids. After extracting the total alkaloid into methanol using a Soxhlet extractor, a few milligrams of the extract was transferred to a separatory funnel, buffered to pH 4.7, the bromocresol green (BCG solution (10-4 M was added, mixed and extracted with CHCl3 until a yellow color was observed in the CHCl3 layer, indicating the presence of the alkaloid. The crude extracts were also investigated by the standard methods of Dragendorf, Wagner and Meyer for the presence of alkaloids.   "n"nResults: Investigation of the 12 plant samples for the presence of alkaloids by the standard reagents of Dragendorf, Wagner, and Meyer showed that only Camelia sinensis (flowers, Echium amoenum Fisch & Mey (flowers, and Stachys (aerial parts are devoid

  20. Potential of solid state fermentation for production of ergot alkaloids

    OpenAIRE

    Trejo Hernandez, M.R.; Raimbault, Maurice; Roussos, Sevastianos; Lonsane, B. K.

    1992-01-01

    Production of total ergot alkaloids by #Claviceps fusiformis$ in solid state fermentation was 3.9 times higher compared to that in submerged fermentation. Production was equal in the case of #Claviceps purpurea$ but the spectra of alkaloids were advantageous with the use of solid state fermentation. The data establish potential of solid state fermentation which was not explored earlier for production of ergot alkaloids. (Résumé d'auteur)

  1. The Total Synthesis Problem of linear multivariable control. II - Unity feedback and the design morphism

    Science.gov (United States)

    Sain, M. K.; Antsaklis, P. J.; Gejji, R. R.; Wyman, B. F.; Peczkowski, J. L.

    1981-01-01

    Zames (1981) has observed that there is, in general, no 'separation principle' to guarantee optimality of a division between control law design and filtering of plant uncertainty. Peczkowski and Sain (1978) have solved a model matching problem using transfer functions. Taking into consideration this investigation, Peczkowski et al. (1979) proposed the Total Synthesis Problem (TSP), wherein both the command/output-response and command/control-response are to be synthesized, subject to the plant constraint. The TSP concept can be subdivided into a Nominal Design Problem (NDP), which is not dependent upon specific controller structures, and a Feedback Synthesis Problem (FSP), which is. Gejji (1980) found that NDP was characterized in terms of the plant structural matrices and a single, 'good' transfer function matrix. Sain et al. (1981) have extended this NDP work. The present investigation is concerned with a study of FSP for the unity feedback case. NDP, together with feedback synthesis, is understood as a Total Synthesis Problem.

  2. Total Synthesis, Structure Revision, and Absolute Configuration of (−)-Brevenal

    OpenAIRE

    Fuwa, Haruhiko; Ebine, Makoto; Bourdelais, Andrea J.; Baden, Daniel G.; Sasaki, Makoto

    2006-01-01

    Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki–Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promo...

  3. Total synthesis of furospongolide and related furanolipid analogues as potential anti-tumour agents

    OpenAIRE

    Harrold, Donal Patrick

    2014-01-01

    This thesis details the design, development and execution of innovative methodology in the total synthesis of the terpene-derived marine natural product, furospongolide. It also outlines the synthetic routes used to prepare a novel range of furanolipids derivatives and subsequent evaluation of their potential as antitumour agents. The first chapter is a review of the literature describing efforts undertaken towards the synthesis of biologically active furanosesterterpenoid marine natural prod...

  4. Total synthesis of (3S, 5R, 3'S, 5'R)-capsorubin

    Energy Technology Data Exchange (ETDEWEB)

    Frederico, Daniel; Constantino, Mauricio G.; Donate, Paulo M. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Quimica

    2009-07-01

    The total synthesis of enantiomerically enriched (3S, 5R, 3'S, 5'R)-capsorubin (1) by aldol condensation of (1R, 4S)-1-(4-hydroxy-1,2,2-trimethyl-cyclopentyl)ethanone (2a) and crocetindial (3) is described. An alternative, short eight-step synthesis of the optically active compound 2a (ee 89%) is also reported. (author)

  5. Enantioselective modular synthesis of cyclohexenones: total syntheses of (+)-crypto- and (+)-infectocaryone.

    Science.gov (United States)

    Franck, Géraldine; Brödner, Kerstin; Helmchen, Günter

    2010-09-01

    A modular synthesis of cyclohexenones is described and applied to the first enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation, nucleophilic allylation, and ring-closing metathesis. On the way to (+)-cryptocaryone, a catch and release strategy involving an iodolactonization/elimination and a regioselective C-acylation were used. PMID:20677804

  6. Stereoselective total synthesis of the potent anti-asthmatic compound CMI-977 (LDP-977)

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Luiz Carlos; Farina, Lui Strambi; Ferreira, Marco Antonio Barbosa, E-mail: ldias@iqm.unicamp.br [Universidade de Campinas (UNICAMP), SP (Brazil). Instituto de Quimica

    2013-02-15

    A short and efficient stereoselective total synthesis of CMI-977 (LDP-977), a potent and orally active anti-asthmatic compound, was developed. The key steps involve a highly diastereoselective Mukaiyama oxidative cyclization, which provides the trans-THF (tetrahydrofuran) unit and a Seyferth-Gilbert homologation to construct the triple bond in the target molecule. The synthesis of the key chiral building block was performed using Jacobsen hydrolytic kinetic resolution. (author)

  7. Total Synthesis of Ionic Liquid Systems for Dissolution of Lunar Simulant

    Science.gov (United States)

    Sharpe, Robert J.; Karr, Laurel J.; Paley, Mark S.

    2010-01-01

    For purposes of Space Resource Utilization, work in the total synthesis of a new ionic liquid system for the extraction of oxygen and metals from lunar soil is studied and described. Reactions were carried out according to procedures found in the chemical literature, analyzed via Thin-Layer Chromatography and 1H Nuclear Magnetic Resonance Spectroscopy and purified via vacuum distillation and rotary evaporation. Upon final analysis via 1H NMR, it was found that while the intermediates of the synthesis had been achieved, unexpected side products were also present. The mechanisms and constraints of the synthesis are described as well as the final results of the project and recommendations for continued study

  8. Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations.

    Science.gov (United States)

    Nicolaou, K C; Wang, Yanping; Lu, Min; Mandal, Debashis; Pattanayak, Manas R; Yu, Ruocheng; Shah, Akshay A; Chen, Jason S; Zhang, Hongjun; Crawford, James J; Pasunoori, Laxman; Poudel, Yam B; Chowdari, Naidu S; Pan, Chin; Nazeer, Ayesha; Gangwar, Sanjeev; Vite, Gregory; Pitsinos, Emmanuel N

    2016-07-01

    From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy. PMID:27266267

  9. Enantioselective Total Synthesis of (+)-Steenkrotin A and Determination of Its Absolute Configuration.

    Science.gov (United States)

    Pan, Saiyong; Gao, Beiling; Hu, Jialei; Xuan, Jun; Xie, Hujun; Ding, Hanfeng

    2016-01-18

    The first enantioselective total synthesis of (+)-steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction, two sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro-aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)-steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis. PMID:26660855

  10. Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H

    Directory of Open Access Journals (Sweden)

    Masashi Yokoya

    2015-08-01

    Full Text Available The first total synthesis of (±-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3 stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H via the C3-C4 double bond formation in an early stage based on the Avendaño’s protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenylmethyl-piperazine-2,5-dione (8 in 18 steps (8.3% overall yield. The synthesis provides unambiguous evidence supporting the original structure of renieramycin I.

  11. Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement.

    Science.gov (United States)

    David, Nadège; Pasceri, Raffaele; Kitson, Russell R A; Pradal, Alexandre; Moody, Christopher J

    2016-07-25

    A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A. PMID:27346186

  12. Steroidal glyco alkaloids and molluscicidal activity of Solanum asperum Rich. fruits

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Tania M.S. [Instituto Multidisciplinar em Saude, Vitoria da Conquista, BA (Brazil). Campus Avancado Anisio Teixeira]. E-mail: sarmento@pesquisador.cnpq.br; Camara, Celso A. [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Quimica; Freire, Kristerson R.L.; Silva, Thiago G. da; Agra, Maria de F.; Bhattacharyya, Jnanabrata [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica

    2008-07-01

    Bioassay-guided fractionation of the alkaloidal extract of the green fruits of Solanum asperum afforded a new compound, solanandaine along with solasonine and solamargine. The total crude alkaloids as well as the isolated pure alkaloids exhibited significant molluscicidal activity. (author)

  13. A stereoselective total synthesis of the novel triquinane sesquiterpene cucumin E

    OpenAIRE

    Mehta, Goverdhan; Umarye, Jayant D

    2001-01-01

    A total synthesis of cucumin E, a recently isolated triquinane natural product with a new carbon framework, has been achieved. The key step is the flash vacuum pyrolysis (FVP)-induced cyclobutane fragmentation in a readily available pentacyclic caged dione to deliver the triquinane skeleton with functionalization in all the three five-membered rings suitable for further elaboration to the natural product.

  14. Total Synthesis and Complete Stereostructure of a Marine Macrolide Glycoside, (-)-Lyngbyaloside B.

    Science.gov (United States)

    Fuwa, Haruhiko; Yamagata, Naoya; Okuaki, Yuta; Ogata, Yuya; Saito, Asami; Sasaki, Makoto

    2016-05-10

    We have described in detail the total synthesis of both the proposed and correct structures of (-)-lyngbyaloside B, which facilitated the elucidation of the complete stereostructure of this natural product. Our study began with the total synthesis of 13-demethyllyngbyaloside B, in which an esterification/ring-closing metathesis (RCM) strategy was successfully used for the efficient construction of the macrocycle. We also established reliable methods for the introduction of the conjugated diene side chain and the l-rhamnose residue onto the macrocyclic framework. However, the esterification/RCM strategy proved ineffective for the parent natural product because of the difficulties in acylating the sterically encumbered C-13 tertiary alcohol; macrolactionization of a seco-acid was also extensively investigated under various conditions without success. We finally completed the total synthesis of the proposed structure of (-)-lyngbyaloside B by means of a macrolactonization that involves an acyl ketene as the reactive species. However, the NMR spectroscopic data of our synthetic material did not match those of the authentic material, which indicated that the proposed structure must be re-examined. Inspection of the NMR spectroscopic data of the natural product and molecular mechanics calculations led us to postulate that the configuration of the C-10, C-11, and C-13 stereogenic centers had been incorrectly assigned in the proposed structure. Finally, our revised structure of (-)-lyngbyaloside B was unambiguously verified through total synthesis. PMID:27112323

  15. Enantioselective total synthesis of a novel polyketide natural product(+)-integrasone, an HIV-1 integrase inhibitor

    OpenAIRE

    Mehta, Goverdhan; Roy, Subhrangsu

    2005-01-01

    Enantioselective total synthesis of the recently isolated, novel polyketide natural product (+)-integrasone has been accomplished from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone. An enzymatically desymmetrized epoxyquinone building block has been elaborated through a series of regio-, chemo- and stereocontrolled steps to the final bicyclic framework of the natural product.

  16. Total synthesis of the putative structure of the novel triquinane natural product isocapnellenone

    OpenAIRE

    Mehta, Goverdhan; Murthy, Sai Krishna A; Umarye, Jayant D

    2002-01-01

    A total synthesis of the ‘putative structure’ 7, attributed to the novel triquinane sesquiterpene isolated recently from two Buddelia species has been accomplished. The spectral data for 7 is a complete mismatch with those reported for the natural product and warrants a revision of the assigned structure.

  17. The first total synthesis of the novel triquinane natural products pleurotellol and pleurotellic acid

    OpenAIRE

    Mehta, Goverdhan; Murthy, Sai Krishna A

    2003-01-01

    The first total synthesis of the triquinane based sesquiterpenoid antibiotics (±)-pleurotellol and (±)-pleurotellic acid isolated from the fermentation broth of Pleurotellus hypnophilus have been accomplished. The triquinane based bis-enone system obtained via photo-thermal metathesis in a caged pentacyclic dione has been elaborated to the natural products through carefully crafted functional group transformations.

  18. First total synthesis of yanuthones: novel farnesylated epoxycyclohexenoid marine natural products

    OpenAIRE

    Mehta, Goverdhan; Pan, Subhas Chandra

    2005-01-01

    The total synthesis of the recently isolated marine natural products of mixed biosynthetic origin, yanuthones A, 13 C and 22-deacylyanuthone A,has been accomplished following a short regio- and stereocontrolled approach involving the key intermediacy of 2-farnesyl-p-benzoquinone.

  19. First Total Synthesis of an Analogue of (±)—Hypargenin B

    Institute of Scientific and Technical Information of China (English)

    AnPaiLI; HuiWANG; 等

    2002-01-01

    First total synthesis of (±)-hypargenin B methyl ether 2 was accomplished via a strategy of AC→ABC,in which CrO3/H2O/NaOAc/HOAc system was utilized for introducing 7-keto group in order to aviod dehydration of benzyl tertiary alcohol.

  20. First Total Synthesis of an Analogue of (±)-Hypargenin B

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    First total synthesis of (±)-hypargenin B methyl ether 2 was accomplished via a  strategy of AC→ABC, in which CrO3/H2O/NaOAc/HOAc system was utilized for introducing  7-keto group in order to avoid dehydration of benzyl tertiary alcohol.

  1. First Total Synthesis of (±)-Abieta-8, 11, 13-trien-7β-ol

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The first total synthesis of (±)-abieta-8, 11, 13-trien-7β-ol (7) was accomplished via a strategy of AC→ABC, in which the reduction of the ketone 6 with LiAlH4 gave exclusively the title compound.

  2. Buchner and Beyond: Arene Cyclopropanation as Applied to Natural Product Total Synthesis

    OpenAIRE

    Reisman, Sarah E.; Nani, Roger R.; Levin, Sergiy

    2011-01-01

    Buchner and Curtius first reported the cyclopropanation of arenes in 1885. Since the initial discovery, the Buchner reaction has been the subject of significant research by both physical and synthetic organic chemists. Described herein is a brief overview of the Buchner reaction and related arene cyclopropanation processes, with an emphasis on their application to natural product total synthesis.

  3. A Biomimetic Strategy to Access the Silybins: Total Synthesis of (−)-Isosilybin A

    OpenAIRE

    McDonald, Benjamin R.; Nibbs, Antoinette E.; Scheidt, Karl A.

    2014-01-01

    We report the first asymmetric, total synthesis of (−)-isosilybin A. A late-stage catalytic biomimetic cyclization of a highly functionalized chalcone is employed to form the characteristic benzopyranone ring. A robust and flexible approach to this chalcone provides an entry to the preparation of the entire isomeric family of silybin natural products.

  4. The Taumycin A Macrocycle: Asymmetric Total Synthesis and Revision of Relative Stereochemistry

    OpenAIRE

    deGruyter, Justine N.; Maio, William A.

    2014-01-01

    The first asymmetric total synthesis and revision of the relative configuration of the 12-membered taumycin A macrocycle is described. Key to the success of this work was a novel α-keto ketene macrocyclization that provided an efficient means by which to access two diastereomers of the desired macrolide without the need to employ additional coupling agents or unnecessary oxidation state adjustments.

  5. Cinchona alkaloid squaramide catalyzed enantioselective hydrazination/cyclization cascade reaction of α-isocyanoacetates and azodicarboxylates: synthesis of optically active 1,2,4-triazolines.

    Science.gov (United States)

    Zhao, Mei-Xin; Bi, Hong-Lei; Zhou, Hao; Yang, Hui; Shi, Min

    2013-09-20

    An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazolines in excellent yields (up to 99%) and good to excellent enantioselectivities (up to 97% ee) under mild conditions. PMID:23984761

  6. The Stille reaction in natural product synthesis : the total synthesis of 14,15-anhydrovirginiamycin M2

    OpenAIRE

    Jordan, Stuart Ian

    1997-01-01

    The thesis describes synthetic studies directed towards the total synthesis of 14,15-anhydrovirginiamycin M2, a streptogramin antibiotic of the virginiamycin family. This novel natural product shows pronounced antibacterial activity against a wide range of potentially lethal bacteria. The Introduction summarises the main therapeutic uses, isolation, structural determination, biosynthesis, and mode of action of the virginiamycins. Also included is a review of synthetic approaches which have b...

  7. Asymmetric Synthesis of Decahydroquinolines via Organocatalysis: Total Synthesis of (+)-Lycoposerramine Z and (-)-Cermizine B

    OpenAIRE

    Luque Corredera, Carlos

    2014-01-01

    [eng] 1) The treatment of a tert-butyl beta-keto ester tethered to an omega-amino monoprotected group with crotonaldehyde using LiOH as the base, furnishes domino reactions involving the consecutive formation of two C-C bonds and one C-N bond in a sequence that comprises an intermolecular Michael process, followed by intramolecular aldol and aza-Michael reactions. This general methodology for the diastereoselective synthesis of 5-oxodecahydroquinolines implies a biscyclization and the format...

  8. The Total Synthesis of Insect Antifeedant (-)-Dihydroclerodin Starting from R-(-)-Carvone

    OpenAIRE

    Meulemans, T.M.

    2000-01-01

    The first total synthesis of the natural enantiomer of the insect-antifeedant dihydroclerodin ( 1 ) and lupulin C ( 268 ) has been achieved in 18 and 17 steps respectively starting from R-(-)-carvone ( 2 ). A new strategy was developed in which the hexahydrofuro[2,3- b ]furan fragment was introduced in the beginning of the synthesis, via a remarkably diastereoselective Mukaiyama reaction of silyl enol ether 135 with 2-methoxy-hexahydrofuro[2,3- b ]furan ( 156 ), which gave only two of the pos...

  9. A Pot-Economical Approach to the Total Synthesis of Sch-725674.

    Science.gov (United States)

    Bodugam, Mahipal; Javed, Salim; Ganguly, Arghya; Torres, Jessica; Hanson, Paul R

    2016-02-01

    A pot-economical total synthesis of antifungal Sch-725674, 1, is reported. The approach takes advantage of a number of one-pot, sequential transformations, including a phosphate tether-mediated one-pot, sequential RCM/CM/chemoselective hydrogenation protocol, a one-pot tosylation/acrylation sequence, and a one-pot, sequential Finkelstein reaction/Boord olefination/acetonide deprotection procedure to streamline the synthesis route by reducing isolation and purification procedures, thus saving time. Overall, an asymmetric route has been developed that is efficiently accomplished in seven pots from phosphate (S,S)-triene and with minimal purification. PMID:26760683

  10. Novel Euglenoid Derived Alkaloid

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Disclosed herein is a purified toxin isolated from Euglena sanguinea. More specifically the toxin, termed euglenophycin, is an alkaloid having herbicidal and...

  11. Occurrence of halogenated alkaloids.

    Science.gov (United States)

    Gribble, Gordon W

    2012-01-01

    Once considered to be isolation artifacts or chemical "mistakes" of nature, the number of naturally occurring organohalogen compounds has grown from a dozen in 1954 to >5000 today. Of these, at least 25% are halogenated alkaloids. This is not surprising since nitrogen-containing pyrroles, indoles, carbolines, tryptamines, tyrosines, and tyramines are excellent platforms for biohalogenation, particularly in the marine environment where both chloride and bromide are plentiful for biooxidation and subsequent incorporation into these electron-rich substrates. This review presents the occurrence of all halogenated alkaloids, with the exception of marine bromotyrosines where coverage begins where it left off in volume 61 of The Alkaloids. Whereas the biological activity of these extraordinary compounds is briefly cited for some examples, a future volume of The Alkaloids will present full coverage of this topic and will also include selected syntheses of halogenated alkaloids. Natural organohalogens of all types, especially marine and terrestrial halogenated alkaloids, comprise a rapidly expanding class of natural products, in many cases expressing powerful biological activity. This enormous proliferation has several origins: (1) a revitalization of natural product research in a search for new drugs, (2) improved compound characterization methods (multidimensional NMR, high-resolution mass spectrometry), (3) specific enzyme-based and other biological assays, (4) sophisticated collection methods (SCUBA and remote submersibles for deep ocean marine collections), (5) new separation and purification techniques (HPLC and countercurrent separation), (6) a greater appreciation of traditional folk medicine and ethobotany, and (7) marine bacteria and fungi as novel sources of natural products. Halogenated alkaloids are truly omnipresent in the environment. Indeed, one compound, Q1 (234), is ubiquitous in the marine food web and is found in the Inuit from their diet of whale

  12. Marine Indole Alkaloids

    Directory of Open Access Journals (Sweden)

    Natalie Netz

    2015-08-01

    Full Text Available Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed.

  13. Asymmetric Total Synthesis of Propindilactone G, Part 3: The Final Phase and Completion of the Synthesis.

    Science.gov (United States)

    Liang, Xin-Ting; You, Lin; Li, Yuan-He; Yu, Hai-Xin; Chen, Jia-Hua; Yang, Zhen

    2016-05-01

    Two independent synthetic approaches were evaluated for the final phase of the asymmetric total synthesis of propindilactone G (1). The key steps that led to the completion of the asymmetric total synthesis included: 1) an intermolecular oxidative heterocoupling reaction of enolsilanes to link the core structure to the side chain; 2) an intermolecular Wittig reaction for the formation of the α,β,γ,δ-unsaturated ester; and 3) a regio- and stereoselective OsO4 -catalyzed dihydroxylation of an α,β,γ,δ-unsaturated enone, followed by an intramolecular lactonization reaction to afford the final product. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised. Furthermore, the direct oxidative coupling strategy for ligation of the core of propindilactone G with its side chain may find application in the syntheses of other natural products and complex molecules. PMID:26991640

  14. Diastereoselective total synthesis of (±)-schindilactone a, Part 3: The final phase and completion.

    Science.gov (United States)

    Ren, Wei-Wu; Chen, Zhi-Xing; Xiao, Qing; Li, Yong; Sun, Tian-Wen; Zhang, Zi-Yang; Ye, Qin-Da; Meng, Fan-Ke; You, Lin; Zhao, Ming-Zhe; Xu, Ling-Min; Tang, Ye-Feng; Chen, Jia-Hua; Yang, Zhen

    2012-10-01

    The final phase for the total synthesis of (±)-schindilactone A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1) A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2) a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5) a Dieckmann-type condensation to successfully form the A ring of schindilactone A (1). The chemistry developed for the total synthesis of schindilactone A (1) will shed light on the synthesis of other family members of schindilactone A. PMID:22761030

  15. Total synthesis and absolute configuration assignment of MRSA active garcinol and isogarcinol.

    Science.gov (United States)

    Socolsky, Cecilia; Plietker, Bernd

    2015-02-01

    A short total synthesis of (±)-garcinol and (±)-isogarcinol, two endo-type B PPAPs with reported activity against methiciline resistant Staphylococcus aureus (MRSA), is presented. The separation of framework-constructing from framework-decorating steps and the application of two highly regio- and stereoselective Pd-catalysed allylations, that is, the Pd-catalysed decarboxylative Tsuji-Trost allylation and the diastereoselective Pd-catalysed allyl-allyl cross-coupling, are key elements that allowed the total synthesis to be accomplished within 13 steps starting from acetylacetone. After separation of the enantiomers the absolute configurations of the four natural products (i.e., (-)-garcinol, (+)-guttiferone E (i.e., ent-garcinol), (-)-isogarcinol, and (+)-isoxanthochymol (i.e., ent-isogarcinol)) were assigned based on ECD spectroscopy. PMID:25537962

  16. Stereocontrolled total synthesis of neuroprotectin D1 / protectin D1 and its aspirin-triggered stereoisomer

    OpenAIRE

    Petasis, Nicos A.; Yang, Rong; Winkler, Jeremy W.; Zhu, Min; Uddin, Jasim; Bazan, Nicolas G.; Serhan, Charles N.

    2012-01-01

    Neuroprotectin D1 / protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne prec...

  17. Enantioselective Total Synthesis and Confirmation of the Absolute and Relative Stereochemistry of Streptorubin B

    OpenAIRE

    Hu, Dennis X.; Clift, Michael D.; Lazarski, Kiel E.; Thomson, Regan J.

    2010-01-01

    The enantioselective total synthesis of the pyrrolophane natural product streptorubin B is described. Key steps in the concise route include application of a one-pot enantioselective aldol cyclization/Wittig reaction and an anionic oxy-Cope rearrangement to forge the crucial 10-membered ring. Comparisons between CD-spectra of synthetic and natural samples of streptorubin B, coupled with X-ray crystallography, allowed for the determination of the absolute stereochemistry of this natural produc...

  18. Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.

    Science.gov (United States)

    Balasubramanian, Ranganathan; Raghavan, Bhooma; Begaye, Adrian; Sackett, Dan L; Fecik, Robert A

    2009-01-22

    A stereoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition. PMID:19102699

  19. Total Synthesis of Chiral Biaryl Natural Products by Asymmetric Biaryl Coupling ‡

    OpenAIRE

    Kozlowski, Marisa C.; Morgan, Barbara J.; Linton, Elizabeth C.

    2009-01-01

    This tutorial review highlights the use of catalytic asymmetric 2-naphthol couplings in total synthesis. The types of chirality, chiral biaryl natural products, prior approaches to chiral biaryl natural products, and other catalytic asymmetric biaryl couplings are outlined. The three main categories of chiral catalysts for 2-naphthol coupling (Cu, V, Fe) are described with discussion of their limitations and advantages. Applications of the copper catalyzed couplings in biomimetic syntheses ar...

  20. Studies towards the total synthesis of eleutherobin and other marine natural products

    OpenAIRE

    Mowat, Jeffrey Stuart

    2012-01-01

    The primary focus of the research described in this document relates to the development and application of new synthetic methodologies relevant for the concise construction of four natural products. In Chapter 2, a discussion of our investigation of the total synthesis of eleutherobin (1) is disclosed. Eleutherobin (1), first isolated in 1997 from the rare soft coral Eleutherobia sp., is a member of a class of microtubule stabilising natural products. Although it displays potent cytotoxicity,...

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

    OpenAIRE

    Wen-Ju Bai; Chen Lu; Xiqing Wang

    2016-01-01

    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, sho...

  2. First total synthesis of the marine natural products clavulolactones II and III.

    Science.gov (United States)

    Miller, Charlotte M; Benneche, Tore; Tius, Marcus A

    2015-04-01

    The first total synthesis of the marine prostanoids clavulolactones II and III is presented from an easily accessible chiral, non-racemic cyclopentenone intermediate. Key steps involve selective TBDMS deprotection, selective reduction of the β-side chain and aldol condensation. Clavulolactones II and III were successfully prepared from (S)-4-((tert-butyldimethylsilyl)oxy) cyclopent-2-en-1-one over nine steps, in overall yields of 21 and 7% respectively. PMID:25733336

  3. Organisational culture, organisational learning and total quality management: a literature review and synthesis.

    Science.gov (United States)

    Bloor, G

    1999-01-01

    As health services face increasing pressure to meet the expectations of different stakeholders, they must continuously improve and learn from their experience. Many fail in attempts at continuous improvement programs because managers have not understood the complexity of making changes in organisations with multiple subcultures and interests. This article examines the related concepts of organisational culture, organisational learning and total quality management and shows how a synthesis of this knowledge can assist in developing continuous organisational learning and improvement. PMID:10662226

  4. Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

    OpenAIRE

    John Li; May May Leong; Alastair Stewart; Mark A. Rizzacasa

    2013-01-01

    The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11. Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial red...

  5. Total Synthesis of (±)-Paroxetine by Diastereoconvergent Cobalt-Catalysed Arylation

    OpenAIRE

    Despiau, Carole F; Dominey, Andrew P; Harrowven, David C.; Linclau, Bruno

    2014-01-01

    A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp3–sp2 coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step. A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.

  6. First- and second-generation total synthesis of ciguatoxin CTX3C

    OpenAIRE

    Inoue, Masayuki; Miyazaki, Keisuke; Uehara, Hisatoshi; Maruyama, Megumi; Hirama, Masahiro

    2004-01-01

    More than 20,000 people suffer annually from ciguatera seafood poisoning in subtropical and tropical regions. The extremely low content of the causative neurotoxins, designated as ciguatoxins, in fish has hampered isolation, detailed biological studies, and preparation of anti-ciguatoxin antibodies for detecting these toxins. Furthermore, the large (3 nm in length) and complex molecular structure of ciguatoxins has impeded chemists from completing their total synthesis. In this article, the f...

  7. Total synthesis of (+/-)-11 alpha-hydroxyprogesterone by cyclization of a polyunsaturated epoxide.

    OpenAIRE

    van Tamelen, E E; Faler, D L

    1985-01-01

    The total synthesis of a typical 11-hydroxylated steroid, (+/-)-11 alpha-hydroxyprogesterone, was achieved by picric acid-catalyzed tricyclization of a polyunsaturated epoxide appropriately substituted with ketal, hydroxyl, and acetylenic units. This epoxide was prepared by a multistage sequence featuring two successive alkylations of intermediary, monocyclic sulfones. The first sulfone intermediate was obtained by means of a short sequence starting from levulinic acid and diethyl succinate a...

  8. β-Keto-dioxinones and β,δ-diketo-dioxinones in biomimetic resorcylate total synthesis.

    Science.gov (United States)

    Cookson, Rosa; Barrett, Tim N; Barrett, Anthony G M

    2015-03-17

    Resorcylates are a large group of bioactive natural products that are biosynthesized from acetate and malonate units via the intermediacy of polyketides. These polyketides undergo cyclization reactions to introduce the aromatic core. The bioactivities of the resorcylates including resorcylate macrocyclic lactones include anticancer, antimalarial, mycotoxicity, antifungal, and antibiotic properties, and several compounds in the series are already in use in medicine. Examples are prodrugs derived from mycophenolic acid as immunosuppressants and the Hsp-90 inhibitor, AT13387, which is in phase-II clinical trials for the treatment of small cell lung cancer and melanoma. In consequence of these biological activities, methods for the concise synthesis of diverse resorcylates are of considerable importance. In natural product chemistry, biomimetic total synthesis can have significant advantages including functional group tolerance in key steps, the minimization of the use of protection and deprotection reactions and the shortening of the total number of synthetic steps. This Account provides a description of our adaption of the dioxinone chemistry of Hyatt, Clemens, and Feldman for the synthesis and retro-Diels-Alder reactions of diketo-dioxinones. Such dioxinones, which were synthesized by a range of C-acylation reactions, were found to undergo retro-Diels-Alder reactions on heating to provide the corresponding triketo-ketenes with the loss of acetone. The ketene reactive intermediates were rapidly trapped both inter- and intramolecularly with alcohols to provide the corresponding β,δ,ζ-triketo-esters. These compounds, which consist of keto-enol mixtures, readily undergo cycloaromatization to produce resorcylate esters and macrocyclic lactones. We have established the use of diketo-dioxinones as key general intermediates for the synthesis of diverse resorcylate natural products and for the synthesis of new classes of compounds for the generation of medicinal chemistry

  9. Cytotoxicity of Hymenocallis expansa alkaloids.

    Science.gov (United States)

    Antoun, M D; Mendoza, N T; Ríos, Y R; Proctor, G R; Wickramaratne, D B; Pezzuto, J M; Kinghorn, A D

    1993-08-01

    From the bulbs and leaves of Hymenocallis expansa (Amaryllidaceae), three alkaloid constituents were identified: (+)-tazettine, (+)-hippeastrine, and (-)-haemanthidine. These alkaloids demonstrated significant cytotoxicity when tested against a panel of human and murine tumor cell lines. PMID:8229020

  10. CRINUM; AN ENDLESS SOURCE OF BIOACTIVE PRINCIPLES: A REVIEW. PART 1- CRINUM ALKALOIDS: LYCORINE-TYPE ALKALOIDS

    Directory of Open Access Journals (Sweden)

    John Refaat*, Mohamed S. Kamel , Mahmoud A. Ramadan and Ahmed A. Ali

    2012-07-01

    Full Text Available Crinum is an important Amaryllidaceous plant thanks to the valuable biological and therapeutic activities of its chemical constituents, especially alkaloids. Many Crinum species have been commonly used in traditional medicines worldwide. Long ago, they have been subjected to extensive chemical, cytological and pharmacological investigations. Accordingly, this work comprehensively comprises both the alkaloidal and non-alkaloidal principles of Crinums isolated from 1950 and up to now, together with various biological and toxicological studies conducted on both the total extracts and individual compounds. As being a major common class of Crinum alkaloids, the current part of this review work highlights the lycorine-type alkaloids isolated so far from this plant in addition to their distribution in different Crinum species.

  11. Lycorine alkaloids from Hymenocallis littoralis.

    Science.gov (United States)

    Lin, L Z; Hu, S F; Chai, H B; Pengsuparp, T; Pezzuto, J M; Cordell, G A; Ruangrungsi, N

    1995-11-01

    From Hymenocallis littoralis, one new alkaloid, named littoraline, together with 13 known lycorine alkaloids and one lignan, were isolated. The structure and NMR assignments of this new alkaloid were determined by 1D and 2D NMR techniques. Littoraline showed inhibitory activity of HIV reverse transcriptase, and lycorine and haemanthamine showed potent in vitro cytotoxicity. PMID:7492374

  12. 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…

  13. Polymer-Supported Cinchona Alkaloid-Derived Ammonium Salts as Recoverable Phase-Transfer Catalysts for the Asymmetric Synthesis of α-Amino Acids

    Directory of Open Access Journals (Sweden)

    Carmen Nájera

    2004-04-01

    Full Text Available Alkaloids such as cinchonidine, quinine and N-methylephedrine have been N-alkylated using polymeric benzyl halides or co-polymerized and then N-alkylated, thus affording a series of polymer-supported chiral ammonium salts which have been employed as phase-transfer catalysts in the asymmetric benzylation of an N-(diphenylmethyleneglycine ester. These new polymeric catalysts can be easily recovered by simple filtration after the reaction and reused. The best ee’s were achieved when Merrifield resin-anchored cinchonidinium ammonium salts were employed.

  14. Analysis of Ergot Alkaloids

    Directory of Open Access Journals (Sweden)

    Colin Crews

    2015-06-01

    Full Text Available The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS and liquid chromatography with fluorescence detection (LC-FLD. Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes.

  15. Total synthesis of Herbarin A and B, determination of their antioxidant properties and toxicity in zebrafish embryo model.

    Science.gov (United States)

    Heimberger, Julia; Cade, Hannah C; Padgett, Jihan; Sittaramane, Vinoth; Shaikh, Abid

    2015-03-15

    Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. PMID:25690788

  16. Total Synthesis, Proof of Absolute Configuration, and Biosynthetic Origin of Stylopsal, the First Isolated Sex Pheromone of Strepsiptera

    Czech Academy of Sciences Publication Activity Database

    Lagoutte, Roman; Šebesta, Petr; Jiroš, Pavel; Kalinová, Blanka; Jirošová, Anna; Straka, J.; Černá, K.; Šobotník, Jan; Cvačka, Josef; Jahn, Ullrich

    2013-01-01

    Roč. 19, č. 26 (2013), s. 8515-8524. ISSN 0947-6539 R&D Projects: GA ČR GAP506/10/1466 Institutional support: RVO:61388963 Keywords : asymmetric synthesis * configuration determination * pheromones * total synthesis * Wittig reactions Subject RIV: CC - Organic Chemistry Impact factor: 5.696, year: 2013

  17. Toward the Enantioselective Total Synthesis of Lyngbyatoxin A: On the Stereocontrolled Introduction of the Quaternary Stereogenic Centre

    DEFF Research Database (Denmark)

    Tønder, Janne Ejrnæs; Tanner, David Ackland

    2003-01-01

    This paper deals with an approach to the enantioselective total synthesis of Lyngbyatoxin A, with focus on the stereocontrolled introduction of the quaternary stereogenic centre. The key step in the synthesis involves an enantiospecific Lewis-acid mediated rearrangement of chiral vinyl epoxides...

  18. Main Alkaloids of Peganum harmala L. and Their Different Effects on Dicot and Monocot Crops

    OpenAIRE

    Chi Zhang; Yuanming Zhang; Hua Shao; Xiaoli Huang

    2013-01-01

    Alkaloids with allelopathic activity are not as well-known as other allelochemicals. Our study revealed that total alkaloids from seeds of the medicinal plant Peganum harmala L. possessed significant growth inhibitory effect on four treated plants, with dicot plants (lettuce and amaranth) being more sensitive than the tested monocot plants (wheat and ryegrass). Further investigation led to the isolation of harmaline and harmine as the main active ingredients in the total alkaloids of P. harma...

  19. Enantioselective total synthesis of the novel tricyclic sesquiterpene (−)-sulcatine G. Absolute configuration of the natural product

    OpenAIRE

    Mehta, Goverdhan; Sreenivas, K.

    2002-01-01

    An enantioselective total synthesis of (−)-sulcatine G 4 from the readily available (+)-diquinane diol 6 has been accomplished. This leads to the establishment of the absolute configuration of the natural product (+)-sulcatine G as 1.

  20. 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.

  1. Flexible Total Synthesis of (±)-Aureothin, a Potent Antiproliferative Agent.

    Science.gov (United States)

    Henrot, Matthias; Jean, Alexandre; Peixoto, Philippe A; Maddaluno, Jacques; De Paolis, Michaël

    2016-06-17

    Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α'-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the backbone of the target. Palladium-catalyzed cyanation of an elaborated and isomerizable E,Z dienyl motif followed by Pinner cyclization enabled the construction of the tetrahydrofuran motif while a first approach based on a late-stage oxidation was unsuccessful. PMID:27213834

  2. Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

    Directory of Open Access Journals (Sweden)

    John Li

    2013-12-01

    Full Text Available The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1 is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11. Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1.

  3. Total synthesis of all stereoisomers of eudesm-11-en-4-ol.

    OpenAIRE

    Kesselmans, R.P.W.

    1992-01-01

    In this thesis the total synthesis of all stereoisomers of eudesm-11-en-4-ol e.g. selin-11-en-4α-ol I , intermedeol II , neointermedeol III , paradisiol IV , amiteol V , 7- epi -amiteol VI , 5- epi -neointermedeol VII , and 5- epi -paradisiol VIII is described.The natural occurrences and the difficulties encountered in the structural elucidation of these eudesmanes are described in chapter 1. The eudesm-11-en-4-ols occur in a wide range of plant species, some of which are used in medicine, or...

  4. Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

    OpenAIRE

    Keck, Gary E.; Giles, Robert L.; Cee, Victor J.; Wager, Carrie A.; Yu, Tao; Kraft, Matthew B.

    2008-01-01

    Studies leading to a total synthesis of Epothilones B and D are described. The overall synthetic plan was based on late stage fragment assembly of two segments representing C1-C9 and C10-C21 of the structure. The C1-C9 fragment was prepared by elaboration of commercially available (2R)-3-hydroxy-2-methylpropanoate at both ends of the three carbon unit. Introduction of carbons 1–4 containing the gem-dimethyl unit was achieved in a convergent manner using a diastereoselective addition of a stan...

  5. Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

    Science.gov (United States)

    Dhavan, Atul A; Kaduskar, Rahul D; Musso, Loana; Scaglioni, Leonardo; Martino, Piera Anna

    2016-01-01

    Summary The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds suggests that they could be considered as promising candidates for future developments.

  6. Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.

    Science.gov (United States)

    Kruegel, Andrew C; Gassaway, Madalee M; Kapoor, Abhijeet; Váradi, András; Majumdar, Susruta; Filizola, Marta; Javitch, Jonathan A; Sames, Dalibor

    2016-06-01

    Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids. PMID

  7. Synthesis of derivatives of tetronic acid and pulvinic acid. Total synthesis of norbadione A; Synthese de derives de l'acide tetronique et de l'acide pulvinique. Synthese totale de la norbadione A

    Energy Technology Data Exchange (ETDEWEB)

    Mallinger, A

    2008-11-15

    When vegetables like mushrooms are contaminated by radioactive caesium 137, this radioactive caesium is associated to norbadione A, a natural pigment present in two mushroom species and which can be used as a caesium decorporation agent or maybe as protection agent against ionizing radiations. Within this perspective, this research report describes the biosynthesis and the structure and properties of the norbadione A and of pulvinic acids (physicochemical properties, anti-oxidizing properties). Then, it presents the various tetronic acids (3-acyl-, 3-alkyl-, 3-alkoxy-, 3-aryl-tetronic acids and non 3-substituted tetronic acids), their synthesis path as they are described in the literature, and presents a new synthesis approach using a tandem reaction (with different esters or hydroxy esters) and the synthesis of tetronic acids. The author also proposes a new synthesis way for methyl pulvinates, and finally reports the work on the development of a total synthesis of the norbadione A.

  8. Relativity among starch quantity, polysaccharides content and total alkaloid content of Dendrobium loddigesii%美花石斛茎的淀粉粒数量、多糖含量与生物碱含量的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱华; 滕建北; 蔡毅; 梁洁; 朱意麟; 韦韬

    2011-01-01

    目的:研究美花石斛茎的淀粉粒数量、多糖含量、生物碱含量之间的相关性.方法:显微计数法统计茎的淀粉粒数量,硫酸-蒽酮比色法测定多糖含量,溴甲酚绿比色法测定生物碱含量;Pearson积差相关分析、Kendall's等级相关分析、Spearman’s和谐系数分析研究三者的相关性.结果与结论:美花石斛茎的淀粉粒数量与其多糖含量有极显著的正相关性,而淀粉粒数量及多糖含量均与生物碱含量呈显著的负相关性.%Objective; To find out the relativity among starch quantity, polysaccharides content and total alkaloid content of Dendrobium loddigesii. Method: Microscopy-counting process was applied to starch quantity statistics, sulfuric acid-anthrone colorime-try was used to assay polysaccharides content and bromocresol green colorimetry was used to assay alkaloid content Pearson product moment correlation analysis, Kendall's rank correlation analysis and Spearman's concordance coefficient analysis were applied to study their relativity. Result and Conclusion: Extremely significant positive correlation was found between starch quantity and polysaccharides content, and significant negative correlation between alkaloid content and starch quantity was discovered, as well was between alkaloid content and polysaccharides content

  9. Decision-making regarding total knee replacement surgery: A qualitative meta-synthesis

    Directory of Open Access Journals (Sweden)

    Ong Bie

    2007-04-01

    Full Text Available Abstract Background Knee osteoarthritis is a highly prevalent condition that can result in disability and reduced quality of life. The evidence suggests that total knee replacement surgery (TKR is an effective intervention for patients with severe knee problems, but there is also an unmet need for this treatment in the UK. To help understand the reason for this unmet need, the aim of this study was to explore the factors that influence the decision-making process of TKR surgery by synthesising the available evidence from qualitative research on this topic. Methods A meta-synthesis was undertaken. This involved sevens steps: getting started, deciding what is relevant to the initial interest, reading the studies, determining how the studies are related, translating the studies into one another, synthesising translations, and finally, expressing the synthesis. Second-order and third-order interpretations regarding decision-making in TKR surgery were drawn from the literature. Results Ten qualitative studies were found and are included in the synthesis. The evidence suggests that social and cultural categories of aging have shaped the expectation of knee osteoarthritis, and this in turn shapes patients' expectations of treatment options. The role of the health care professional was the strongest theme to emerge across all ten studies. Coping strategies and life context determine short and longer-term outcomes of TKR. Conclusion The decision-making process regarding TKR surgery is extremely complex, as patients have weigh up numerous considerations before they can make a decision about surgery. By synthesising ten qualitative studies, we have illuminated the importance of the health care professional during this process.

  10. Asymmetric Total Synthesis of Propindilactone G, Part 2: Enantioselective Construction of the Fully Functionalized BCDE Ring System.

    Science.gov (United States)

    Zhang, Jia-Jun; You, Lin; Wang, Yue-Fan; Li, Yuan-He; Liang, Xin-Ting; Zhang, Bo; Yang, Shou-Liang; Su, Qi; Chen, Jia-Hua; Yang, Zhen

    2016-05-01

    The enantioselective synthesis of the fully functionalized BCDE tetracyclic ring system of propindilactone G (A) is reported. Several synthetic methods were developed and applied to achieve this goal, including: 1) an asymmetric Diels-Alder reaction in the presence of Hayashi's catalyst for the synthesis of optically pure key intermediate 3; 2) an intramolecular Pauson-Khand reaction (PKR) for the stereoselective synthesis of the BCDE ring with an all-carbon chiral quaternary center at the C13 position by using the TMS-substituted acetylene as the substrate; and 3) Pd-catalyzed reductive hydrogenolysis for the stereoselective synthesis of the fully functionalized BCDE tetracyclic ring system. The chemistry developed herein provided a greater understanding of the total synthesis propindilactone G (A) and its analogues. PMID:26991420

  11. Microcalorimetry studies of the antimicrobial actions of Aconitum alkaloids.

    Science.gov (United States)

    Shi, Yan-bin; Liu, Lian; Shao, Wei; Wei, Ting; Lin, Gui-mei

    2015-08-01

    The metabolic activity of organisms can be measured by recording the heat output using microcalorimetry. In this paper, the total alkaloids in the traditional Chinese medicine Radix Aconiti Lateralis were extracted and applied to Escherichia coli and Staphylococcus aureus. The effect of alkaloids on bacteria growth was studied by microcalorimetry. The power-time curves were plotted with a thermal activity monitor (TAM) air isothermal microcalorimeter and parameters such as growth rate constant (μ), peak-time (Tm), inhibitory ratio (I), and enhancement ratio (E) were calculated. The relationships between the concentration of Aconitum alkaloids and μ of E. coli or S. aureus were discussed. The results showed that Aconitum alkaloids had little effect on E. coli and had a potentially inhibitory effect on the growth of S. aureus. PMID:26238544

  12. Total Synthesis of Flocoumafen via Knoevenagel Condensation and Intramolecular Ring Cyclization: General Access to Natural Products

    Directory of Open Access Journals (Sweden)

    Mankil Jung

    2012-02-01

    Full Text Available The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1. Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.

  13. Asymmetric total synthesis of (-)-lingzhiol via a Rh-catalysed [3+2] cycloaddition.

    Science.gov (United States)

    Long, Rong; Huang, Jun; Shao, Wenbin; Liu, Song; Lan, Yu; Gong, Jianxian; Yang, Zhen

    2014-01-01

    The development of efficient reactions for the one-pot construction of bicyclic ring systems bearing two quaternary carbon centres at their bridgehead positions represents a significant challenge to synthetic chemistry. The development of new methods capable of overcoming this challenge is highly desirable, because this motif can be found in a wide range of natural products with significant biological activities. Herein, we report an efficient [3+2] cycloaddition reaction between an enal and an alleno rhodium species, which was generated in situ from the corresponding enynol via a retro metal-propargylation reaction, to give [3.3.0] and [3.4.0] bicyclic systems bearing two quaternary atoms at their bridgehead positions. The developed chemistry has been successfully applied to the asymmetric total synthesis of natural product (-)-lingzhiol (4) for the first time in 17 steps. PMID:25483390

  14. Total Synthesis and Anti-Viral Activities of an Extract of Radix isatidis

    Directory of Open Access Journals (Sweden)

    Li-Wei He

    2014-12-01

    Full Text Available Radix isatidis (Banlangen, a famous traditional Chinese medicine, has been used for thousands of years in China due to its anti-viral activity. Through our research, we inferred that the anti-viral activity of Radix isatidis depended on the water-soluble part. Among the components of this extract, the isoquinoline derivative 1 was isolated for the first time and has shown better anti-viral activity than other constituents. In this study, to solve the problem of sourcing sufficient quantities of compound 1, a total synthesis route is described, and several analogues are also evaluated for their anti-viral activities. Among them, compound 8 shown potent anti-viral activity with an IC50 value of 15.3 µg/mL. The results suggested that isoquinoline derivatives possessed potent anti-viral activity and are worthy further development.

  15. Total synthesis of five lipoteichoic acids of Clostridium difficile

    DEFF Research Database (Denmark)

    Hogendorf, Wouter Frederik Johan; Gisch, Nicolas; Schwudke, Dominik;

    2014-01-01

    The emergence of hypervirulent resistant strains have made Clostridium difficile a notorious nosocomial pathogen and has resulted in a renewed interest in preventive strategies, such as vaccines based on (synthetic) cell wall antigens. Recently, the structure of the lipoteichoic acid (LTA) of this...... species has been elucidated. Additionally, this LTA was found to induce the formation of protective antibodies against C. difficile in rabbits and mice. The LTA from C. difficile is isolated as a microheterogenous mixture, differing in size and composition, impeding any structure-activity relationship...... studies. To ensure reliable biological results, pure and well-defined synthetic samples are required. In this work the total synthesis of LTAs from C. difficile with defined chain length is described and the initial biological results are presented....

  16. Stereoselective Total Synthesis of Atractylodemayne A, a Conjugated 2(E),8(Z),10(E)-Triene-4,6-diyne.

    Science.gov (United States)

    Schmidt, Bernd; Audörsch, Stephan

    2016-03-01

    The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence. PMID:26886865

  17. Peloruside B, a Potent Antitumor Macrolide from the New Zealand Marine Sponge Mycale hentscheli: Isolation, Structure, Total Synthesis and Bioactivity

    OpenAIRE

    Singh, A. Jonathan; Xu, Chun-Xiao; Xu, Xiaoming; West, Lyndon M.; Wilmes, Anja; Chan, Ariane; Hamel, Ernest; John H Miller; Peter T. Northcote; Ghosh, Arun K.

    2010-01-01

    Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G2M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis and bioactivity of peloruside B are described in this article. The synthesis ...

  18. Variation and evolution of alkaloid complex in yellow lupine (Lupinus luteus L. during domestication

    Directory of Open Access Journals (Sweden)

    Wiktor Święcicki

    2013-12-01

    Full Text Available A colection of 178 primitive and cultivated forms of Lupinus luteus was analysed with respect to composition and level of alkaloids in seeds. A considerable quantitative and qualitative variation in alkaloids was found in the analysed forms. All analysed primitive forms, not cultivated in Central Europe, contained gramine and lupinine; the majority had sparteine as well. Contrary to the common opinion, yellow lupine has three basic alkaloids, i.e. gramine, lupinine and sparteine. Moreover, a large number of primitive forms showed traces of unidentified alkaline compounds with alkaloid characteristics. It appears that in the course of introduction of yellow lupine to central Europe, the composition and level of its alkaloids have been gradually changing. Their reproduction and natural selection remarkably decreased the number of forms containing gramine as well as the total level of alkaloids in seeds. Cross breeding and screening for low alkaloid bearing forms significantly decreased the total level of gramine as well as the number of forms containing gramine and almost entirely eliminated traces of unidentified alkaloids. One new form was found to have sparteine and only a little of lupinine (total level of alkaloids 0,04%.

  19. Solid-phase extraction and LC-MS analysis of pyrrolizidine alkaloids in honeys.

    Science.gov (United States)

    Beales, Kerrie A; Betteridge, Keith; Colegate, Steven M; Edgar, John A

    2004-10-20

    Strong-cation-exchange, solid-phase extraction of pyrrolizidine alkaloids and their N-oxides from honey samples was followed by reduction of the N-oxides and subsequent analysis of total pyrrolizidine alkaloids using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. A limited survey of 63 preprocessing samples of honey, purposefully biased toward honeys attributed to floral sources known to produce pyrrolizidine alkaloids, demonstrated levels of pyrrolizidine alkaloids up to approximately 2000 parts per billion (ppb) in a sample attributed to Echium plantagineum. Up to 800 ppb pyrrolizidine alkaloids was detected in some honeys not attributed by the collector to any pyrrolizidine alkaloid-producing floral source. No pyrrolizidine alkaloids were detected in approximately 30% of the samples in this limited study, while some honeys showed the copresence of pyrrolizidine alkaloids from multiple floral sources such as E. plantagineum and Heliotropium europaeum. In addition, retail samples of blended honeys (with no labeling to suggest that pyrrolizidine alkaloid-producing floral sources were used in the blends) have been shown to contain up to approximately 250 ppb pyrrolizidine alkaloids. PMID:15479038

  20. Identification of the cytochrome P450 monooxygenase that bridges the clavine and ergoline alkaloid pathways.

    Science.gov (United States)

    Haarmann, Thomas; Ortel, Ingo; Tudzynski, Paul; Keller, Ullrich

    2006-04-01

    Clavines and D-lysergic acid-derived alkaloid amides and alkaloid peptides are two different families of compounds that have the indole-derived tetracyclic metergoline ring system in common. Previous work has shown that D-lysergic acid is biosynthetically derived from clavine alkaloids. Recent cloning and analysis of the ergot alkaloid biosynthesis gene cluster from the D-lysergic acid peptide (ergopeptines)-producing Claviceps purpurea, has shown that it most probably contains all genes necessary for D-lysergic acid synthesis as well as those that encode the assembly of D-lysergic acid peptides, such as ergotamine. To address the role of the oxygenase genes of alkaloid-gene clusters, the only cytochrome P450 monooxygenase gene of this cluster was inactivated by disruption. The resultant mutant accumulated agroclavine, elymoclavine, and chanoclavine in substantial amounts but not ergopeptines. Feeding the mutant with D-lysergic acid restored ergopeptine synthesis; this suggests a block in the conversion of elymoclavine to D-lysergic acid. The gene was designated cloA (for encoding a clavine oxidase, CLOA). Retransformation of the mutant with the intact cloA gene also restored ergopeptine synthesis. These data show that CLOA catalyses the conversion of clavines to D-lysergic acid, it acts as a critical enzyme in the ergot alkaloid gene cluster, and bridges the biosynthesis of the two different families of alkaloids. PMID:16538694

  1. Optimization of processing parameters for extraction of total alkaloids of Rhizoma corydalis in Rhizoma corydalis Dispensing Granules by using Box-Behnken experimental design%Box-Behnken响应面法优化延胡索配方颗粒的提取工艺

    Institute of Scientific and Technical Information of China (English)

    白璐; 贺文娟; 崔春利; 王梅; 郭东艳; 宋忠兴; 唐志书

    2013-01-01

    Objective To optimize the processing parameters and apply for the extraction of the total alkaloids of Rhizoma corydalis in Rhizoma corydalis Dispensing Granules. Method Based on the results of single-factor-a-time-technique, a response surface methodology was employed, with the extraction duration,the ratio of water to sample,the extraction times as the independent variables. The response variable was the extraction rate of total alkaloids of Rhizoma corydalis. Result According to regression equation to determine,the best extraction conditions for the extraction duration were as follows:100 min,thc ratio of water to sample 12. 5: 1 (mL · g-1 ) , extraction three times. Conclusion Under the process conditions, the total alkaloids extraction rate of Rhizoma corydalis is 1. 94% , which was in consistency with the theoretic value and had some practical value.%目的 优选延胡索配方颗粒中延胡索总生物碱提取的工艺条件.方法 采用单因素实验结合Box-Behnken响应面法,以延胡索总生物碱提取率为评价指标进行实验,考察提取时间、水料比和提取次数3个因素对提取工艺的影响.结果 根据回归方程确定的最佳提取工艺条件为:提取时间100 min;水料比12.5∶1 (mL·g-1);提取次数3次.结论 采用该工艺条件,延胡索总生物碱的提取率为1.94%,与理论值预测值接近,具有一定的实用价值.

  2. Metal-Free Catalysis for Efficient Synthesis

    OpenAIRE

    Bah, Juho

    2014-01-01

    The strength of efficient metal-free catalysis will be examined in this thesis. Efforts towards more sustainable processes will be demonstrated through implementation of strategies that meet several of the 12 principles of Green Chemistry.In the first part, a stereoselective total synthesis of multiple alkaloids from the Corynantheine and Ipecac families together with their non-natural analogues will be disclosed. A highly efficient, common synthetic strategy is applied leading to high overal...

  3. Automatic alkaloid removal system.

    Science.gov (United States)

    Yahaya, Muhammad Rizuwan; Hj Razali, Mohd Hudzari; Abu Bakar, Che Abdullah; Ismail, Wan Ishak Wan; Muda, Wan Musa Wan; Mat, Nashriyah; Zakaria, Abd

    2014-01-01

    This alkaloid automated removal machine was developed at Instrumentation Laboratory, Universiti Sultan Zainal Abidin Malaysia that purposely for removing the alkaloid toxicity from Dioscorea hispida (DH) tuber. It is a poisonous plant where scientific study has shown that its tubers contain toxic alkaloid constituents, dioscorine. The tubers can only be consumed after it poisonous is removed. In this experiment, the tubers are needed to blend as powder form before inserting into machine basket. The user is need to push the START button on machine controller for switching the water pump ON by then creating turbulence wave of water in machine tank. The water will stop automatically by triggering the outlet solenoid valve. The powders of tubers are washed for 10 minutes while 1 liter of contaminated water due toxin mixture is flowing out. At this time, the controller will automatically triggered inlet solenoid valve and the new water will flow in machine tank until achieve the desire level that which determined by ultra sonic sensor. This process will repeated for 7 h and the positive result is achieved and shows it significant according to the several parameters of biological character ofpH, temperature, dissolve oxygen, turbidity, conductivity and fish survival rate or time. From that parameter, it also shows the positive result which is near or same with control water and assuming was made that the toxin is fully removed when the pH of DH powder is near with control water. For control water, the pH is about 5.3 while water from this experiment process is 6.0 and before run the machine the pH of contaminated water is about 3.8 which are too acid. This automated machine can save time for removing toxicity from DH compared with a traditional method while less observation of the user. PMID:24783795

  4. Total synthesis, structural, and biological evaluation of stylissatin A and related analogs.

    Science.gov (United States)

    Shaheen, Farzana; Jabeen, Almas; Ashraf, Samreen; Nadeem-Ul-Haque, Muhammad; Shah, Zafar Ali; Ziaee, Muhammad Asad; Dastagir, Nida; Ganesan, A

    2016-09-01

    The natural product cyclic peptide stylissatin A (1a) was reported to inhibit nitric oxide production in LPS-stimulated murine macrophage RAW 264.7 cells. In the current study, solid-phase total synthesis of stylissatin A was performed by using a safety-catch linker and yielded the peptide with a trans-Phe(7) -Pro(6) linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d-allo-Ile in place of l-Ile and a different site for macrocyclization. The resulting product (d-allo-Ile(2) )-stylissatin A (1c) was also found to have the trans-Phe(7) -Pro(6) peptide conformations like rotamer 1b. Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a, 1b, and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2-7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product (1a), the rotamer (1b), and (d-allo-Ile(2) )-stylissatin A (1c) exhibited significant inhibition of NO(.) . Further investigations were focused on 1b, which also inhibited proliferation of T-cells and inflammatory cytokine IL-2 production. The analogs 2-7 weakly inhibited NO(.) production, but strongly inhibited IL-2 cytokine production compared with synthetic peptide 1b. All analogs inhibited the proliferation of T-cells, with analog 7 having the strongest effect. In the analogs, the Pro(6) residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27526945

  5. Effects of total alkaloid of sophora alopecuroids on bladder detrusor muscle activity in diabetic cystopathy rats%苦豆子总碱对糖尿病性膀胱病大鼠逼尿肌活动的影响

    Institute of Scientific and Technical Information of China (English)

    李妍; 孙安; 牛彩琴

    2016-01-01

    Objective To observe the influence of the total alkaloid of sophora alopecuroids L (TASa) on bladder detru-sor muscle activity in diabetic cystopathy(DCP) rats. Methods (1)The diabetic rat model was established by adopting strepto-zotocin(STZ);(2)the urodynamic indicators were detected for establishing the DCP model;(3)the constant temperature perfusion bath tank was adopted to divide the isolated bladder detrusor muscle strips into the control group (normal muscle strip,12 samples) and DCP model group(DCP muscle strip,72 samples),then,the DCP group was subdivided into the TASa group,TASa combined verapamil group,TASa combined phentolamine group,TASa combined indometacin group and TASa combined with atropine group,12 samples in each group. The influence of TASa on the spontaneous contraction of DCP detrusor muscle was investigated. Results TASa could increase the contraction amplitude of bladder detrusor musclen with dose-effect dependence(r=0.89,t=3.39, P0.05). Verapamil could significantly inhibit the TASa action for contracting bladder detrusor mus-cle,but atropine,phetolamine,benzhydramine and indomethacin had no influence. Conclusion TASa may activate calcium ion channel to increase contraction of bladder detrusor muscle.%目的:观察苦豆子总碱(TASa)对糖尿病性膀胱病(DCP)大鼠膀胱逼尿肌活动的影响。方法(1)采用链脲佐菌素法建造糖尿病模型;(2)测定尿流动力学指标确立DCP模型;(3)采用恒温灌流浴槽,将大鼠膀胱逼尿肌离体肌条标本分为对照组(正常肌条,12份)和DCP模型组(DCP肌条,72份),再将DCP模型组分为TASa组、TASa联合异搏定(维拉帕米)组、TASa联合酚妥拉明组、TASa联合苯海拉明组、TASa联合消炎痛(吲哚美辛)组和TASa联合阿托品组,各12份。探讨TASa对DCP逼尿肌自发收缩的影响。结果 TASa能增强DCP膀胱逼尿肌自发收缩的振幅,并具有量效依赖性(r=0.89,t=3.39

  6. Prescription and technology of nux vomica total alkaloids sustained-release tablets%马钱子总生物碱缓释片处方和工艺的研究

    Institute of Scientific and Technical Information of China (English)

    管庆霞; 封文静; 李永吉; 王录娜; 李伟男

    2013-01-01

    Hydroxypropyl methyl cellulose ( HPMC ) as skeleton material was prepared for nux vomica alkaloids sustained-release tablets. This paper established HPLC method for detecting nux vomica alkaloids sustained release tablets and investigated its release rate in vitro. The factors affected release rate also was explored. The results showed that specification and amount of HPMC had significant effect on the release rate, and nux vomica alkaloids sustained release tablets conformed to Higuchi equation. Compared with ordinary tablets, the new tablets had significantly sustained release effect. This method had advantages in preparation, expense appearance of tablets.%以羟丙基甲基纤维素(HPMC)为骨架材料,制备马钱子生物碱缓释片,建立马钱子生物碱缓释片释放度的HPLC测定方法,并考察其体外释放度.采用HPLC测定马钱子生物碱缓释片的体外释放度,并对影响释药的因素进行了单因素考察.羟丙甲纤维素(HPMC)的规格和用量对释药速率有显著影响,马钱子生物碱缓释片的体外释放曲线基本符合Higuchi方程.本法制备的缓释片比普通片具有明显的缓释作用.该制备工艺简单易行,生产成本低,片剂外观及可压性良好.

  7. Development of a strategy for the asymmetric synthesis of polycyclic polyprenylated acylphloroglucinols via N-amino cyclic carbamate hydrazones: application to the total synthesis of (+)-clusianone.

    Science.gov (United States)

    Garnsey, Michelle R; Lim, Daniel; Yost, Julianne M; Coltart, Don M

    2010-11-19

    A broadly applicable asymmetric synthetic strategy utilizing N-amino cyclic carbamate alkylation that provides access to the various stereochemical permutations of a common structural motif found in many polycyclic polyprenylated acylphloroglucinols is described. The utility of this methodology is demonstrated through the first asymmetric total synthesis of the antiviral agent (+)-clusianone. PMID:20977254

  8. Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

    Directory of Open Access Journals (Sweden)

    Yiyang Liu

    2014-10-01

    Full Text Available Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge.

  9. Gas Chromatography-mass Spectrometry (GC-MS analysis of alkaloids isolated from Epipremnum aureum (Linden and Andre Bunting

    Directory of Open Access Journals (Sweden)

    Anju Meshram

    2015-02-01

    Full Text Available Recent advances in the use of GC coupled to MS have allowed a chemically guided isolation of uncommon and bioactive alkaloids. The present study was aimed to focus on the extraction and screening of alkaloids from Epipremnum aureum (Linden and Andre Bunting. It has been observed that the plant is very rich in alkaloids and the modified method employed for the extraction of alkaloid is efficient and selective, where the interference of other secondary metabolites is negligible. The identification of each compound was made through gas chromatography-mass spectrometry (GC-MS. A total of twenty six structurally different alkaloids were identified for the first time from this plant. E. aureum is highly rich in alkaloids and twenty six different alkaloids were characterized. The present study may help in the field of natural products’ chemistry and pharmaceuticals as well as drug discovery science and technology.

  10. Total synthesis and structural confirmation of the marine natural product Dysinosin A: a novel inhibitor of thrombin and Factor VIIa.

    Science.gov (United States)

    Hanessian, Stephen; Margarita, Roberto; Hall, Adrian; Johnstone, Shawn; Tremblay, Martin; Parlanti, Luca

    2002-11-13

    The structure and absolute configuration of the marine antithrombotic product dysinosin A was confirmed by total synthesis. The strategy involved disconnections to three subunits, of which two were synthesized from the readily available l-glutamic acid, d-leucine, and d-mannitol. The Grubbs olefin metathesis carbocyclization reaction was utilized to prepare two intermediates. PMID:12418860

  11. A new isochroman-4-one derivative from the peel of Musa sapientum L. and its total synthesis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A new isochroman-4-one, 7,8-dihydroxy-3-methylisochroman-4-one was isolated from water soluble fraction of Musa sapientum L. Its structure was determined by spectroscopic evidences and its total synthesis has also been reported. The compound showed potent antihypertensive activity.

  12. Concise synthetic approaches to naturally occurring β-hydroxyphenylarsonic: first total synthesis of papanerine, its derivative, and praecansone B

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xue; Lee, Yong Rok [Yeungnam Univ., Gyeongsan (Korea, Republic of); Kim, Sung Hong [Korea Basic Science Institute, Daegu (Korea, Republic of)

    2012-04-15

    The total synthesis of biologically interesting β-hydroxyphenylarsonic, papanerine (1), its derivative 2, praecansone B (3), and pongapinone A (4) has been accomplished starting from commercially available 2,4-dihydroxyacetophenone or 6-methoxy-2,4-dihydroxyacetophenone in 3 steps by a convergent strategy through ben zopyran formations, O-methylation, and coupling reactions.

  13. First total synthesis of (+)-broussonetine W: glycosidase inhibition of natural product & analogs.

    Science.gov (United States)

    Song, Ying-Ying; Kinami, Kyoko; Kato, Atsushi; Jia, Yue-Mei; Li, Yi-Xian; Fleet, George W J; Yu, Chu-Yi

    2016-06-14

    The first total synthesis of (+)-broussonetine W (4), a naturally-occurring pyrrolidine iminosugar isolated from the traditional Chinese medical plant Broussonetia kazinoki SIEB (Moraceae), has been completed through a concise synthetic route starting from the readily available d-arabinose derived cyclic nitrone 10 in 11 steps and 31% overall yield, with regioselective installation of the α,β-unsaturated ketone functional group by the elimination of HBr from α-bromoketone as the key step. A number of analogs of (+)-broussonetine W (4) with variable side chain length, different polyhydroxylated pyrrolidine core configurations or saturated cyclohexanones have also been prepared to explore the glycosidase inhibition and the preliminary structure-activity relationship of this intriguing class of compounds. Glycosidase inhibition studies identified the natural product (+)-broussonetine W (4) as a selective and potent inhibitor of β-galactosidase (IC50 = 0.03 μM), while its enantiomer was a selective and potent inhibitor of α-glucosidase (IC50 = 0.047 μM). It was found that the configuration of the polyhydroxylated pyrrolidine ring played a key role on their glycosidase inhibitory activities. The length of side chain and α,β-unsaturated ketone functional group also exhibited some effect on their glycosidase inhibition. PMID:27184090

  14. Protecting-group-free and catalysis-based total synthesis of the ecklonialactones.

    Science.gov (United States)

    Hickmann, Volker; Alcarazo, Manuel; Fürstner, Alois

    2010-08-18

    A concise and protecting-group-free total synthesis of optically pure ecklonialactones A (1) and B (2) is described. The successful route to these oxylipins isolated from various brown algae involves five transition-metal-catalyzed transformations in the longest linear sequence of 13 steps. The first chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate to the commercial butenolide 11, which was controlled by Carreira's carvone-derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis effected by the ruthenium indenylidene complex 22 for the formation of the five-membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of the unusually high propensity of the oxirane of the ecklonialactones for ring-opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new generation of highly tolerant yet remarkably efficient molybdenum alkylidyne complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis acidity of the molybdenum center and are not able to nucleophilically open the fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene was accomplished either by Lindlar reduction or with the aid of nickel boride. PMID:20698670

  15. Combining the [2,3] Sigmatropic Rearrangement and Ring-Closing Metathesis Strategies for the Synthesis of Spirocyclic Alkaloids. A Short and Efficient Route to (+/-)-Perhydrohistrionicotoxin

    DEFF Research Database (Denmark)

    Tanner, David Ackland; Hagberg, Lars; Poulsen, Anders

    1999-01-01

    This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6. The methodology has been applied to a short...... route is potentially enantioselective, and key steps were the [2,3] sigmatropic rearrangement of 11 to 12 via the corresponding allylic selenide (86% yield) and ruthenium-catalyzed RCM of 13 to 14 (80%). (C) 1999 Elsevier Science Ltd. All rights reserved....

  16. Toward the Total Synthesis of Scleritodermin A: Preparation of the C1-N15 Fragment

    OpenAIRE

    Sellanes, Diver; Manta, Eduardo; Serra, Gloria

    2007-01-01

    The synthesis of the C1-N15 fragment of the marine natural product Scleritodermin A has been accomplished through a short and stereocontrolled sequence. Highlights of this route include the synthesis of the novel ACT fragment and the formation of the α-keto amide linkage by the use of a highly activated α, β-ketonitrile.

  17. Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

    OpenAIRE

    Thilo Focken; Stephen Hanessian

    2014-01-01

    A review of the synthesis of natural products and bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be summarized, as well as an overview of the synthesis of the employed phosphonamide reagents.

  18. Biosynthesis of tylophora alkaloids

    International Nuclear Information System (INIS)

    Using labelled precursors, biosynthesis of the tylophora alkaloids, tylophorine, tylophorinidine and tylophorinide has been investigated in Tylophora asthmatica plants. The radioactive precursors, phenylalanine-2-14C, benzoic acid-1-14C, benzoic acid-ring 14C, acetate-2-14C, ornithine-5-14C, acetate-2-14C, ornithine-5-14C and cinnamic acid-2-14C were administered to the plants individually by wick technique. Tylophorine was isolated in each case and assayed for its radioactivity to find out the incorporation of the label into it. The results indicate that: (1) phenylalanine via cinnamic acid is an important precursor in the biosynthesis of tylophorine (2) orinithine participates in tylophorine biosynthesis via pyrroline and (3) tylophorinidine may be a direct precursor of tylophorine. (M.G.B.)

  19. hERG Blockade by Iboga Alkaloids.

    Science.gov (United States)

    Alper, Kenneth; Bai, Rong; Liu, Nian; Fowler, Steven J; Huang, Xi-Ping; Priori, Silvia G; Ruan, Yanfei

    2016-01-01

    The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 µM) or by extraction from T. iboga (3.53 ± 0.16 µM); ibogaine's principal metabolite noribogaine (2.86 ± 0.68 µM); and voacangine (2.25 ± 0.34 µM). In contrast, the IC50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was >50 µM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (K i) for the entire set of compounds, including 18-MC, ranged from 0.71 to 3.89 µM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure-activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel. PMID:25636206

  20. Total Synthesis of Clavosolide A via Tandem Allylic Oxidation/Oxa-Conjugate Addition Reaction

    Science.gov (United States)

    Baker, Joseph B.; Kim, Hyoungsu; Hong, Jiyong

    2015-01-01

    The tandem allylic oxidation/oxa-conjugate addition reaction promoted by the gem-disubstituent effect in conjunction with the NHC-mediated oxidative esterification was explored for the facile synthesis of clavosolide A. PMID:26236051

  1. Bis(indolyl)methane alkaloids: Isolation, bioactivity, and syntheses

    Digital Repository Service at National Institute of Oceanography (India)

    Praveen, P.; Parameswaran, P.S.; Majik, M.S.

    Author version: Synthesis - Stuttgart, vol.47; 2015; 1827-1837 Bisindolyl Methane Alkaloids: Isolation, Bioactivity and Syntheses P. J. Praveen,a,b P. S. Parameswaran*b, M. S. Majik*c aCSIR-National Institute of Oceanography, Bioorganic Chemistry... Laboratory, Dona Paula Goa- India; bCSIR-National Institute of Oceanography Regional centre, Kochi, India, Email:param@nio.org; cDepartment of Chemistry, Goa University, Goa 403 206, India, Email:majikms@gmail.com Abstract Bis...

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

    OpenAIRE

    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 tetr...

  3. Total synthesis of peloruside A via kinetic lactonization and relay RCM cyclization reactions (and identification of iso-peloruside A)

    OpenAIRE

    Hoye, Thomas R.; Jeon, Junha; Kopel, Lucas C.; Ryba, Troy D.; Tennakoon, Manomi A.; Wang, Yini

    2010-01-01

    A convergent total synthesis of peloruside A (1) is described. The key strategic features are a diastereoselective lactonization to generate a C5-C9 valerolactone from the C2-symmetric ketone 4, which comprises C1–C9 of 1, and a relay ring closing metathesis (RRCM) reaction to produce a dehydrovalerolactone 20, which embodies C13–C19. A new isomer of 1, the valerolactone iso-peloruside A (iso-1), was identified.

  4. Genotoxicity of pyrrolizidine alkaloids.

    Science.gov (United States)

    Chen, Tao; Mei, Nan; Fu, Peter P

    2010-04-01

    Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs. PMID:20112250

  5. Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A.

    Science.gov (United States)

    Wada, Hiroki; Williams, Huw E L; Moody, Christopher J

    2015-12-01

    The power of rhodium-carbene methodology in chemistry is demonstrated by the synthesis of a structurally complex polyazole antibiotic. Plantazolicin A, a novel soil-bacterium metabolite, comprises a linear array of 10 five-membered rings in two pentacyclic regions that derive from ribosomal peptide synthesis followed by extensive posttranslational modification. The compound possesses potent antimicrobial activity, and is selectively active against the anthrax-causing organism. A conceptually different synthesis of plantazolicin A is reported in which the key steps are the use of rhodium(II)-catalyzed reactions of diazocarbonyl compounds to generate up to six of the seven oxazole rings of the antibiotic. NMR spectroscopic studies and molecular modeling reveal a likely dynamic hairpin conformation with a hinge region around the two isoleucine residues. The compound has modest activity against methicillin-resistant Staphylococcus aureus (MRSA). PMID:26473502

  6. Depth-related alkaloid variation in Mediterranean Aplysina sponges.

    Science.gov (United States)

    Putz, Annika; Kloeppel, Anne; Pfannkuchen, Martin; Brümmer, Franz; Proksch, Peter

    2009-01-01

    Total amounts and patterns of bromoisoxazoline alkaloids of Aplysina sponges from Croatia (Mediterranean Sea) were analyzed along an underwater slope ranging from 1.8 to 38.5 m. Total amounts of alkaloids varied from sample to sample and showed no correlation with depth. In contrast, striking differences of alkaloid patterns were found between sponges from shallow sites (1.8-11.8 m) and those collected from deeper sites (11.8-38.5 m). Sponges from shallow depths consistently exhibited alkaloid patterns typical for Aplysina aerophoba with aerophobin-2 (2) and isofistularin-3 (3) as main constituents. Sponges from deeper sites (below 11.8 m) resembled Aplysina cavernicola with aerothionin (4) and aplysinamisin-1 (1) as major compounds. The typical A. cavernicola pigment 3,4-dihydroxyquinoline-2-carboxylic acid (6), however, could not be detected in A. aerophoba sponges but was replaced by the A. aerophoba pigment uranidine (5) which appeared to be present in all sponge samples analyzed. During transplantation experiments sponges from sites below 30 m featuring the A. cavernicola chemotype of bromoisoxazoline alkaloids were translocated to shallower habitats (10 m). The alkaloid patterns in transplanted sponges were found to be stable over a period of 12 months and unaffected by this change in depth. In a further experiment, clones of Aplysina sponges from shallow depths of 5-6 m resembling the A. aerophoba chemotype were either kept in situ under natural light conditions or artificially shaded by excluding photosynthetically active radiation (PAR). Neither 4 nor 1 were detected in artificially shaded sponges over an observation period of 12 months. In summary, two chemically distinct types of Aplysina sponges were discovered in this study that proved to be remarkably stable with regard to the bromoisoxazoline patterns and unaffected either by changing the light conditions or depth. It is not clear presently whether the Aplysina sponges collected from depths Aplysina

  7. Survey of Iranian Plants For Saponins Alkaloids Flavonoids And Tannins. IV

    OpenAIRE

    M.H. Salehi Surmaghi; Y. Aynehchi GH. Amin; Z. Mahmoodi

    1992-01-01

    A total of 149 plant extracts representing 49 different families has been screened for saponins, flavonoids, tannins and alkalodids. positive tests obtained were 145 (97) for saponins 74 (50%) for alkaloids 16 (51%) for fiavonoisds and 60 (40%) for tannins.

  8. Total Chemical Synthesis,Assembly of Human Torque Teno Virus Genome

    Institute of Scientific and Technical Information of China (English)

    Zheng Hou; Gengfu Xiao

    2011-01-01

    Torque teno virus(TTV)is a nonenveloped virus containing a single-stranded,circular DNA genome of approximately 3.8kb.We completely synthesized the 3808 nucleotides of the TTV(SANBAN isolate)genome,which contains a hairpin structure and a GC-rich region.More than 100 overlapping oligonucleotides were chemically synthesized and assembled by polymerise chain assembly reaction(PCA),and the synthesis was completed with splicing by overlap extension(SOEing).This study establishes the methodological basis of the chemical synthesis of a viral genome for use as a live attenuated vaccine or gene therapy vector.

  9. Total Synthesis and Structure-Activity Relationship of Glycoglycerolipids from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2014-06-01

    Full Text Available Glycoglycerolipids occur widely in natural products, especially in the marine species. Glycoglycerolipids have been shown to possess a variety of bioactivities. This paper will review the different methodologies and strategies for the synthesis of biological glycoglycerolipids and their analogs for bioactivity assay. In addition, the bioactivities and structure-activity relationship of the glycoglycerolipids are also briefly outlined.

  10. Total synthesis of desoxycyclomarin C and the cyclomarazines A and B.

    Science.gov (United States)

    Barbie, Philipp; Kazmaier, Uli

    2016-07-01

    Removing the β-hydroxy group from the prenylated tryptophan moiety of cyclomarins simplifies the synthesis of these interesting natural products significantly, without having a noteworthy effect on the anti-tuberculosis activity of the cyclomarins. In contrast, cyclomarazines did not show biological activity. PMID:27241664

  11. Biosynthesis and Total Synthesis Studies on The Jadomycin Family of Natural Products

    OpenAIRE

    Sharif, Ehesan U.; O’Doherty, George A.

    2012-01-01

    Jadomycins are unique angucycline polyketides, which are produced by soil bacteria Streptomyces venezuelae under specific nutrient and environmental conditions. Their unique structural complexity and biological activities have engendered extensive study of the jadomycin class of natural compounds in terms of biological activity, biosynthesis, and synthesis.

  12. Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

    Directory of Open Access Journals (Sweden)

    Bernhard Westermann

    2011-04-01

    Full Text Available Enantiomerically highly enriched unsaturated β-ketoesters bearing a quaternary stereocenter can be utilized as building blocks for the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC as the key step.

  13. FIVE NEW NORDITERPENOID ALKALOIDS FROM ACONITUM SINOMONTANUM

    Institute of Scientific and Technical Information of China (English)

    FENG-PENG WANG; CHONG-SHENG PENG; XI-XIAN JIAN; DONG-LIN CHEN

    2001-01-01

    From the roots of A conitum sinomontanum, five new norditerpenoid alkaloids, sinomontanitines A (1) and B (2), sinomontanines A (3), B (4) and C (5), were isolated together with the known alkaloids lappaconitine (6) and ranaconitine (7), The structures of the new alkaloids were determined by spectral analysis.

  14. Antimicrobial activity of benzylisoquinoline alkaloids.

    Science.gov (United States)

    Villar, A; Mares, M; Rios, J L; Canton, E; Gobernado, M

    1987-04-01

    The antimicrobial in vitro activity of 14 benzylisoquinoline alkaloids was investigated by agar diffusion and agar dilution methods against several genera of microorganisms that included Streptococcus, Staphylococcus, Bacillus, Lysteria, Escherichia, Salmonella, Klebsiella, Pseudomonas, Enterobacter, Serratia, Shigella, Mycobacterium and Candida. Anolobine was the most active compound against grampositive bacteria with MIC90 between 12 and 50 mg/l; less active were anonaine, lysicamine and liriodenine. All the alkaloids of the noraporphine and oxoaporphine groups, with the exception of isopiline, showed activity against Mycobacterium phlei (MIC 6-25 mg/l). Candida albicans ATCC26555 was inhibited by anonaine, nornantenine and xylopine (MIC 3-12 mg/l). None of the alkaloids tested had a significant activity against gramnegative rods. The action against susceptible microorganisms was bactericidal. PMID:3615557

  15. Molecular Toxicology of Pyrrolizidine Alkaloids

    OpenAIRE

    Kim, Hea-Young

    1994-01-01

    Pyrrolizidine alkaloids are cytotoxic, carcinogenic, and anti-carcinogenic in vivo and in vitro, and they produce many hazardous effects in humans and animals. Pyrrolizidine alkaloids (PAs) also cross-link with DNA and/or protein. However, whether such cross-linking is important to the toxic action of PAs is not known. In addition, the exact mechanism underlying these DNA cross-links or cytotoxicity is also not clear. In three separate studies, I characterized the nature of PA-induced DNA ...

  16. The distribution of inole alkaloids in different organs of Catharanthus roseus G. Don. (Vinca rosea L

    Directory of Open Access Journals (Sweden)

    Hassan Ebrahimzadeh

    1996-08-01

    Full Text Available The study of alkaloid extract of the leaf of Vinca rosea by TLC showed the existence of 13 bands, 7 bands of them were: Serpentine, Vincristine, Vinblastine, Ajmaline, Catharantine, Vindoline and Ajmalicine. The existence of these 7 alkaloids was confirmed in the young leaves, old leaves and the roots of the plant by HPLC. Furthermore, two alkaloids with the short retention times and one alkaloid with the medium retention time in the young leaf, three alkaloids with the short retention time and one alkaloid with long retention time in the old leaf, and one alkaioid with the short retention time and two other alkaloids with the long retention times in the root, were observed."nThe study of absorption spectrum of alkaloid extract and its comparison with absorption spectrum of ajmalicine showed that the latter can be used for drawing a standard curve and detecting the amount of total alkaloids. The total alkaloids in fresh root, old leaf and young leaf were 2.1 mg , 1.3 mg and 0.9 mg/g respectively, Vindoline and Catharantine were major alkaloids in all of them. However, their amount were more in the root (1.2 mg/ g of fresh material, 0.85 in the old leaf and 0.38 in the young leaf. Vinblastine existed in all three samples but its amount was more in the root {0.22 mg per gramme of the fresh material in the root, 0.26 in the young leaf and 0.003 in the old leaf."nAjmalicine was detected only in the leaf and its amount was more in young leaf than the old leaf (0.141 mg/g of the fresh material in the young leaf and 0.013 in the old leaf. Serpentine was seen in all of the studied organs but its amount was more in the young leaf than other organs (0.192 mg/ g of the fresh material in the young leaf, 0.11 in the root and 0.07 in the old leaf. Ajmaline existed in all of the organs in minute amount but in the old leaf was more (0 .07 mg/g of the fresh material in the old !eaf,0.044 in the young leaf and 0.04 in the root . The percentage of unknown

  17. Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib and Other Salinosporamides

    Directory of Open Access Journals (Sweden)

    Barbara C. Potts

    2010-03-01

    Full Text Available The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1 is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1.

  18. ISOLATION AND PURIFICATION OF ALKALOIDS FROM PLUMULA NELUMBINIS BY DOUBLE-COLUMN ADSORPTION CHROMOTOGRAPHY

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The performance of adsorption and separation for liensinine, isoliensinine and neferine was studied by double-column adsorption chromatography using macroporous adsorption and cation exchange resins. The alkaloid extract with 49.2% total contents by mass representing 10.6% liensinine, 10.6% isoliensinine and 28.0% neferine respectively was prepared by D72 cation exchange resins, in which most of the impurities were water-soluble alkaloids. Furthermore,the alkaloid extract with 82.6% total contents by mass containing 33.1%, 15.0% and 34.5% of the three adsorbates respectively was prepared by double-column adsorption chromatography using AKS-W macroporous adsorption and D72 cation exchange resins. As a result, the content of single and total alkaloids has been greatly increased by the double-column adsorption chromatography.

  19. The Efficient and Enantiospecific Total Synthesis of Cyclopenta[b]phenanthrenes Structurally-related to Neurosteroids

    OpenAIRE

    Qian, Mingxing; Covey, Douglas F.

    2010-01-01

    We report an efficient synthesis of cyclopenta[b]phenanthrenes functionalized at C-3 and C-8 from an optically pure Hajos-Parrish ketone. The key step is a neutral alumina catalyzed Michael addition of a Hajos-Parrish ketone derivative (4) to 1,7-octadien-3-one (2) in 98% yield. This Michael addition product went through Krapcho decarbomethoxylation, aldol condensation, lithium liquid ammonia reduction, Wacker oxidation and acid catalyzed cyclization to form cyclopenta[b]phenanthrene (1a) in ...

  20. Total Synthesis of Two 4, 5-Dioxo-seco-eudesmane Sesquiterpenes

    Institute of Scientific and Technical Information of China (English)

    Li Jing FANG; Chen Xi ZHANG; Jin Chun CHEN; Guo Jun ZHENG; Yu Lin LI

    2005-01-01

    A facile synthetic route to two seco-eudesmane, 4, 5-dioxo-10-epi-4, 5-seco-γeudesmane (1) and 4, 5-dioxo-10-epi-4, 5-seco-γ-eudesmol (2) from (+)-dihydrocarvone has been described. Avoiding expensive reagents, this highly economic method especially suits for the synthesis of 4, 5-seco-eudesman-type and ophianon-type sesquiterpenes with a double bond at position 11 and 12.

  1. Total synthesis of the aristolochic acids, their major metabolites, and related compounds.

    Science.gov (United States)

    Attaluri, Sivaprasad; Iden, Charles R; Bonala, Radha R; Johnson, Francis

    2014-07-21

    Plants from the Aristolochia genus have been recommended for the treatment of a variety of human ailments since the time of Hippocrates. However, many species produce the highly toxic aristolochic acids (AAs), which are both nephrotoxic and carcinogenic. For the purposes of extensive biological studies, a versatile approach to the synthesis of the AAs and their major metabolites was devised based primarily on a Suzuki-Miyaura coupling reaction. The key to success lies in the preparation of a common ring-A precursor, namely, the tetrahydropyranyl ether of 2-nitromethyl-3-iodo-4,5-methylendioxybenzyl alcohol (27), which was generated in excellent yield by oxidation of the aldoxime precursor 26. Suzuki-Miyaura coupling of 27 with a variety of benzaldehyde 2-boronates was accompanied by an aldol condensation/elimination reaction to give the desired phenanthrene intermediate directly. Deprotection of the benzyl alcohol followed by two sequential oxidation steps gave the desired phenanthrene nitrocarboxylic acids. This approach was used to synthesize AAs I-IV and several other related compounds, including AA I and AA II bearing an aminopropyloxy group at position-6, which were required for further conversion to fluorescent biological probes. Further successful application of the Suzuki-Miyaura coupling reaction to the synthesis of the N-hydroxyaristolactams of AA I and AA II then allowed the synthesis of the putative, but until now elusive, N-acetoxy- and N-sulfonyloxy-aristolactam metabolites. PMID:24877584

  2. Palladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (-)-Aspewentins A, B, and C.

    Science.gov (United States)

    Liu, Yiyang; Virgil, Scott C; Grubbs, Robert H; Stoltz, Brian M

    2015-09-28

    The direct α-vinylation of carbonyl compounds to form a quaternary stereocenter is a challenging transformation. It was discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (-)-aspewentins A, B, and C is demonstrated. PMID:26230413

  3. Influence of the Total Gas Flow at Different Reaction Times for CVD-Graphene Synthesis on Polycrystalline Nickel

    Directory of Open Access Journals (Sweden)

    M. P. Lavin-Lopez

    2016-01-01

    Full Text Available Optimization of the total gas flow (CH4+H2 during the reaction step for different reaction times for CVD-graphene synthesis on polycrystalline nickel foil using an atmospheric pressure set-up is reported. A thickness value related to number of graphene layers in each of the synthesized samples was determined using an Excel-VBA application. This method assigned a thickness value between 1 and 1000 and provided information on the percentage of each type of graphene (monolayer, bilayer, and multilayer deposited onto the polycrystalline nickel sheet. The influence of the total gas flow during the reaction step and the reaction time was studied in detail. Optical microscopy showed that samples were covered with different types of graphene, such as multilayer, few-layer, bilayer, and monolayer graphene. The synthesis variables were optimized according to the thickness value and the results were verified by Raman spectroscopy. The best conditions were obtained with a reaction temperature of 980°C, a CH4/H2 flow rate ratio of 0.07 v/v, a reaction time of 1 minute, and a total gas flow of 80 NmL/min. In the sample obtained under the optimized conditions, 80% of the area was covered with monolayer graphene and less than 1% with multilayer graphene.

  4. Quaternary alkaloids of tinospora species.

    Science.gov (United States)

    Bisset, N G; Nwaiwu, J

    1983-08-01

    The occurrence of quaternary alkaloids in TINOSPORA (and PARABAENA) species (Menispermaceae) has been studied. The main components were generally the protoberberine bases berberine and palmatine, with jatrorrhizine an occasional minor constituent, and the aporphine base magnoflorine. Choline was also often present. Only magnoflorine was detected in the PARABAENA material examined. PMID:17404996

  5. Lycopodium alkaloids from Palhinhaea cernua

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fu-Wei [Graduate University of Chinese Academy of Sciences, Beijing (China); Luo, Ji-Feng; Wang, Yue-Hu, E-mail: wangyuehu@mail.kib.ac.cn [Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences (China); Sun, Qian-Yun; Yang, Fu-Mei [Key Laboratory of Chemistry for Natural Products, Guizhou Province and Chinese Academy of Sciences (China); Liu, Fang [College of Landscape and Horticulture, Yunnan Agricultural University (China); Long, Chun-Lin, E-mail: long@mail.kib.ac.cn [College of Life and Environmental Sciences, Minzu University of China, Beijing, (China)

    2012-07-01

    Two new Lycopodium alkaloids, acetyllycoposerramine M and palcernine A were isolated from whole plant extracts of Palhinhaea cernua L. together with ten previously identified compounds. The structures of the new compounds were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses using the Flack parameter. (author)

  6. Recent approaches to the total synthesis of phytoprostanes, isoprostanes and neuroprostanes as important products of lipid oxidative stress and biomarkers of disease

    Czech Academy of Sciences Publication Activity Database

    Jahn, Emanuela; Durand, T.; Galano, J. M.; Jahn, Ullrich

    2014-01-01

    Roč. 108, č. 4 (2014), s. 301-319. ISSN 0009-2770 Institutional support: RVO:61388963 Keywords : lipids * oxidative stress * phytoprostanes * isoprostanes * neuroprostanes * total synthesis Subject RIV: CC - Organic Chemistry Impact factor: 0.272, year: 2014

  7. Total Synthesis of Plakilactones C, B and des-Hydroxyplakilactone B by the Oxidative Cleavage of Gracilioether Furanylidenes.

    Science.gov (United States)

    Norris, Matthew D; Perkins, Michael V

    2016-08-01

    A chemoselective oxidative cleavage of synthetic gracilioether B, 11-epi-gracilioether C benzoate, and des-hydroxygracilioether C with pyridinium chlorochromate, which proceeds with loss of the furanyl acetate, has enabled total synthesis and stereochemical elucidation of the marine sponge metabolites (4R,6R)-plakilactone C, (4R,6R,9R)-plakilactone B, and (4R,6R)-des-hydroxyplakilactone B. des-Hydroxygracilioether C, the putative biosynthetic precursor to hippolachnin A, was also found to undergo a facile ene cyclization on treatment with SnCl4. PMID:27359169

  8. Influence of Some Heavy Metals on Growth, Alkaloid Content and Composition in Catharanthus roseus L.

    Science.gov (United States)

    Srivastava, N. K.; Srivastava, A. K.

    2010-01-01

    Shoot biomass production, alkaloid content and composition as influence by cadmium, manganese, nickel and lead at uniform dose of 5 mM were investigated in Catharanthus roseus plants grown in sand culture. Treatment with Mn, Ni, and Pb significantly enhanced total root alkaloid accumulation. Cd and Ni treatment resulted in two-fold where as Pb treatment resulted in three fold increase in serpentine content of roots. The non-significant affect on biomass suggests that plants can withstand metal stress at the level tested with positive affect on root alkaloid content. PMID:21969751

  9. An analysis of Sorghum halepense’s behavior in presence of tropane alkaloids from Datura stramonium extracts

    Directory of Open Access Journals (Sweden)

    Butnariu Monica

    2012-07-01

    Full Text Available Abstract Background This study aimed to quantify the allelopathic potential of Datura stramonium (Jimson weed. Sorghum halepense (Johnsongrass tolerance was assessed by germinating, seed and growing seedlings, dosing of photo-synthesis pigments, followed by treatment with D. stramonium extract tropane alkaloids. Results Preliminary chemical analysis of the extracts showed the presence of alkaloids. The presence of alkaloids was confirmed through HPLC–UV system analysis. Various concentrations of analytic purity alkaloids had similar effects on germination and development of S. halepense’s root systems with those of extracts from of D. stramonium. Germination was not affected by any of the tested extracts, but growth was inhibited by the presence of tropane alkaloids. Extracts had effects at higher alkaloid concentrations. Seedlings of S. halepense developed toxicity symptoms in the presence of alkaloid extracts, but the occurrence of several chlorotic and necrotic areas was noticed in the flower extract biotest. Conclusions Results show that the tested species is sensitive to alkaloids in their growth environment. This research justifies the fact that aqueous extracts from D. stramonium are adequate to the situations in which S. halepense becomes damaging.

  10. Total synthesis and structural validation of cyclodepsipeptides solonamide A and B

    DEFF Research Database (Denmark)

    Kitir, Betül; Baldry, Mara; Ingmer, Hanne; Olsen, Christian Adam

    2014-01-01

    from the marine bacterium Photobacterium halotolerance and were found to inhibit virulence gene expression in the serious human pathogen, Staphylococcus aureus. They act by interfering with the agr quorum sensing system and show resemblance to the endogenous S. aureus quorum sensing peptide......, autoinducing peptide I (AIP-I). To enable more comprehensive studies, we embarked on the chemical synthesis of solonamides A and B. The key synthetic steps were formation of the (R)-β-hydroxy-fatty-acids by stereo-selective aldol reactions and a cyclative macrolactamization, which proceeded under highly dilute...

  11. Enantioselective total synthesis of (−)-epoxyquinols A and B. Novel, convenient access to chiral epoxyquinone building blocks through enzymatic desymmetrization

    OpenAIRE

    Mehta, Goverdhan; Islam, Kabirul

    2004-01-01

    Following our recent total synthesis of the biologically potent natural products epoxyquinols A and B in racemic form, we have now accomplished the total synthesis of the (−)-epoxyquinols A and B, anti-podes of the angiogenesis inhibiting natural products, through a protocol that involves enzymatic desymmetrization of a versatile epoxyquinone derivative, readily available from the Diels–Alder adduct of cyclopentadiene and p-benzoquinone.

  12. Studies of Genetic Variation of Essential Oil and Alkaloid Content in Boldo (Peumus boldus).

    Science.gov (United States)

    Vogel, H; Razmilic, I; Muñoz, M; Doll, U; Martin, J S

    1999-02-01

    Boldo is a tree or shrub with medicinal properties native to Chile. The leaves contain alkaloids and essential oils. Variation of total alkaloid concentration, of the alkaloid boldine, and essential oil components were studied in different populations from northern, central, and southern parts of its geographic range and in their progenies (half-sib families). Total alkaloid concentration showed genetic variation between progenies of the central population but not between populations. Boldine content found in concentrations of 0.007 to 0.009% did not differ significantly between populations. Principal components of the essential oil were determined genetically, with highest values for ascaridole in the population of the north and for P-cymene in the south. Between half-sib families genetic variation was found in the central and northern populations for these components. The high heritability coefficients found indicate considerable potential for successful selection of individuals for these characters. PMID:17260243

  13. 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.

  14. Aporphine and tetrahydroprotoberberine alkaloids from the leaves of Guatteria friesiana (Annonaceae) and their cytotoxic activities

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Emmanoel Vilaca; Cruz, Pedro Ernesto O. da, E-mail: emmanoelvc@gmail.com [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Departamento de Quimica; Marques, Francisco A.; Barison, Andersson; Maia, Beatriz Helena L.N.S. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Centro Politecnico. Departamento de Quimica; Pinheiro, Maria Lucia B. [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil). Departamento de Quimica; Ruiz, Ana Lucia T.G.; Marchetti, Gabriela M.; Carvalho, Joao Ernesto de [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Centro Pluridisciplinar de Pesquisas Quimicas, Biologicas e Agricolas. Divisao de Farmacologia e Toxicologia

    2013-05-15

    Phytochemical investigation of the leaves of Guatteria friesiana (Annonaceae) afforded three new isoquinoline alkaloids, 13-hydroxy-discretinine, 6,6a-dehydroguatteriopsiscine and 9-dehydroxy-1-methoxy-dihydroguattouregidine. Eight known alkaloids were also isolated, 13-hydroxy-2,3,9,10-tetramethoxyprotoberberine, guatteriopsiscine, lysicamine, liriodenine, atherospermidine, lanuginosine, 7,8-dihydro-8-hydroxypalmatine and palmatine. 13-Hydroxy- 2,3,9,10-tetramethoxyprotoberberine was only obtained by synthesis and is being reported as a natural product for the first time. The structures of the isolated alkaloids were established by extensive analysis of 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometric (MS) data, as well as by comparison with data reported in the literature. The in vitro cytotoxic activity of the major alkaloids was evaluated against tumor and non-tumor cell lines. All of the alkaloids evaluated were determined to be inactive based on National Cancer Institute (NCI/USA) criteria. However, the alkaloid palmatine exhibited a cytostatic effect on MCF-7 (breast) and U251 (glioma) human tumor cell lines, with GI{sub 50} values lower than 20.0 Greek-Small-Letter-Mu mol L{sup -}1 (10.5and 16.2 Greek-Small-Letter-Mu molL{sup -1}, respectively), suggesting a selective cytotoxic action (author)

  15. Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus.

    Science.gov (United States)

    Zhu, Wei; Yang, Bingxian; Komatsu, Setsuko; Lu, Xiaoping; Li, Ximin; Tian, Jingkui

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress. PMID:26284098

  16. Binary Stress Induces an Increase in Indole Alkaloid Biosynthesis in Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Wei eZhu

    2015-07-01

    Full Text Available Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to that in control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress.

  17. Isolation and Characterization of Antineoplastic Alkaloids from Catharanthus Roseus L. Don. Cultivated in Egypt

    OpenAIRE

    Shams, Khaled A; Nazif, Naglaa M; Abdel Azim, Nahla S; Abdel Shafeek, Khaled A; El-Missiry, Mostafa M.; Ismail, Shams I; Seif El Nasr, Medhat M

    2009-01-01

    Vinblastine and vincristine (the antileukemic agents) were isolated, in a pure form, from Catharanthus roseus L. Don., cultivated in Egypt, by several chromatographic techniques. Five modified methods for the preparation of total alkaloids were carried out. All the isolated mixtures were evaluated by HPLC and HPTLC analyses. The antineoplastic alkaloids; vinblastine and vincristine, were isolated by the use of vacuum liquid chromatographic column on silica gel : aluminium oxide (1:1) mixed be...

  18. Influence of Some Heavy Metals on Growth, Alkaloid Content and Composition in Catharanthus roseus L.

    OpenAIRE

    Srivastava, N. K.; A.K. Srivastava

    2010-01-01

    Shoot biomass production, alkaloid content and composition as influence by cadmium, manganese, nickel and lead at uniform dose of 5 mM were investigated in Catharanthus roseus plants grown in sand culture. Treatment with Mn, Ni, and Pb significantly enhanced total root alkaloid accumulation. Cd and Ni treatment resulted in two-fold where as Pb treatment resulted in three fold increase in serpentine content of roots. The non-significant affect on biomass suggests that plants can withstand meta...

  19. Monitoring the catalytic synthesis of glycerol carbonate by real-time attenuated total reflection FTIR spectroscopy

    NARCIS (Netherlands)

    Calvino-Casilda, V.; Mul, G.; Fernandez, J.F.; Rubio-Marcos, F.; Banares, M.A.

    2011-01-01

    In situ Attenuated Total Reflectance FTIR spectroscopy was used to study the carbonylation of glycerol with urea. Cobalt oxide nanoparticles, Co3O4, hierarchically dispersed on zinc oxide microparticles, ZnO, were used as catalysts. The present work demonstrates that in situ real-time attenuated tot

  20. Total Synthesis of Trimethoprim%甲氧苄啶的全合成

    Institute of Scientific and Technical Information of China (English)

    冀亚飞; 李前荣

    2001-01-01

    对甲酚为起始原料,以总收率40.6%的高收率合成了杀菌增效剂甲氧苄啶.对 甲酚进行溴化、水解反应得到4-羟基-3,5-二溴苯甲醛;该化合物以甲醇钠甲醇溶液 进行甲氧基化反应获得4-羟基-3,5-二甲氧基苯甲醛的酚钠盐,然后直接以硫酸二甲 酯进行甲基化反应得到3,4,5-三甲氧基苯甲醛;用其通过与甲醇钠、丙烯氰的甲醇溶 液反应得到肉桂氰衍生物;该衍生物先经碱催化的1,3-质子转移异构化到烯醚结构, 再与甲醇加成,直接与胍缩合环化,最终得到甲氧苄啶.%Antibacterial synergist trimethoprim was synthesized from p-cresol in an overall yield as high as 40. 6%. p-cresol was brominated and hydrolyzed to give 3, 5-dibromo-4-hydroxyben- zaldehyde, which was methoxylated by methanolic sodium methoxide associated with cuprous chloride and dimethyfformamide(DMF)as catalyst at 125℃ (ca. 0.SMPa)to provide sodium phenolate of 3,5- dimethoxy-4-hydroxybenzaldehyde, from which 3,4,5-trimethoxybenzaldehyde was obtained by methy lation directly with dimethylsuffate in aqueous sodium hydroxide. Efficient synthesis of trimethoprim from 3,4,5-trimethoxybenzaldehyde was accomplished by condensation with methanolic sodium methox ide, methanol and acrylonitrile via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitrile converted into the enol ether, followed by addition with methanol at 90℃ (ca. 0.05MPa)and cyclo condensation directly with guanidine in dimethyl sulfoxide(DMSO)at 110℃ with the removal of methanol. "One-pot" method was used in the synthesis starting from economical, convenient and envi ronmental awareness.

  1. Sol–gel auto-combustion synthesis of totally immiscible NiAg alloy

    International Nuclear Information System (INIS)

    Highlights: ► Chemically synthesized immiscible NiAg alloy nanoparticles without protecting matrix. ► A chemical method providing both a nonequilibrium thermal process and a good mixing of precursors. ► Observation of extinction planes in NiAg alloy. -- Abstract: Immiscible crystalline NiAg alloy was successfully synthesized by the newly developed sol–gel auto-combustion method. The structure and composition were examined by X-ray diffraction (XRD) and high resolution transmission electron microscope (HRTEM). All evidence supports that homogeneous NiAg alloy with FCC structure was synthesized. The differential thermal analysis and thermogravimetry (DTA–TG) measurement shows that the alloy has a good thermal stability until 315 °C. Unusually some extinction planes are observed in the XRD pattern and HRTEM images. The random distribution of atoms and the large difference between Ni and Ag atom form factors should be regarded as the main reasons for the observation of the extinction planes. The quenching like nonequilibrium thermal process in the combustion is taken as the key factor in the synthesis of immiscible alloy. And the addition of ethylene glycol in the precursors is found to benefit the formation of NiAg alloy.

  2. Total synthesis of proanthocyanidin A1, A2, and their stereoisomers.

    Science.gov (United States)

    Sharma, Pradeep K; Romanczyk, Leo J; Kondaveti, Leelakrishna; Reddy, Bollu; Arumugasamy, Jeeva; Lombardy, Richard; Gou, Yanni; Schroeter, Hagen

    2015-05-15

    The first novel stereoselective synthesis of naturally occurring A1 (1) and A2 proanthocyanidins (2) has been achieved. The key synthetic steps involved (a) the formation of a coupled product (13 or 14) between an open chain C-ring C-4 hydroxyethoxy analogue of either (+)-catechin or (-)-epicatechin with 5,7,3',3'-tetra-O-benzyl-(+)-catechin/-(-)-epicatechin in the presence of bentonite clay K-10, (b) removal of benzyl protecting groups under mild catalytic hydrogenation conditions to form the desired A-type compound in situ as a mixture of diastereomers via ketal/oxonium ion/carbonium ion formation, and (c) separation of the diasteromers via silica gel column chromatography. The structures of A1 and A2 proanthocyanidins were unequivocally established by analytical comparison to the natural products. Following this methodology, an additional six diastereomers of proanthocyanidins A1 and A2 have been synthesized. A plausible mechanism for the formation of the A-type linkage in proanthocyanidins has been proposed. PMID:25927567

  3. Total synthesis of the large non-ribosomal peptide polytheonamide B

    Science.gov (United States)

    Inoue, Masayuki; Shinohara, Naoki; Tanabe, Shintaro; Takahashi, Tomoaki; Okura, Ken; Itoh, Hiroaki; Mizoguchi, Yuki; Iida, Maiko; Lee, Nayoung; Matsuoka, Shigeru

    2010-04-01

    Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 = 68 pg ml-1, mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic D- and L-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30 Å in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity.

  4. First Total Synthesis of Hyacinthacine A6 from the Protected Derivative of Polyhydroxylated Pyrrolidine

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tao-xiang; ZHOU Ling; AO Xiao-ping

    2008-01-01

    (1S,2R,3R,5R,7aR)-1,2-Dihydroxy-3-hydroxymethy1-5-methylpyrrolizidine(hyacinthacine A6,1) was synthesized by Wittig's methodology via the reaction of aldehyde 6,prepared from the partially protected derivative of polyhydroxylatcd pyrrolidine,with appropriated ylides,followed by cyclization through the internal reductive amination process of the resulting a,β-unsaturated ketone 7,and total deprotection.

  5. Pyrrolizidine alkaloids of senecio sp from Peru

    Directory of Open Access Journals (Sweden)

    Liliana Ruiz Vásquez and Matías Reina Artiles

    2011-01-01

    Full Text Available Six pyrrolizidine alkaloids (PAs (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon, F. oxysporum fs. lycopersici (Scheldt and F. solani (Mart, no significant activity being observed.

  6. Pyrrolizidine alkaloids of Senecio sp from Peru

    International Nuclear Information System (INIS)

    Six pyrrolizidine alkaloids (PAs) (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic) were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon), F. oxysporum fs. lycopersici (Scheldt) and F. solani (Mart), no significant activity being observed. (author)

  7. Pyrrolizidine alkaloids of Senecio sp from Peru

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Vasquez, Liliana; Reina Artiles, Matias [Instituto de Productos Naturales y Agrobiologia, CSIC, Tenerife (Spain); Gonzalez Coloma, Azucena [Instituto de Ciencias Agrarias (ICA), CSIC, Madrid (Spain); Cabrera Perez, Raimundo [Universidad de La Laguna (ULL), Tenerife (Spain). Unidad de Fitopatologia, Facultad de Biologia; Ruiz Mesia, Lastenia [Universidad Nacional de la Amazonia Peruana (LIPNAA-UNAP), AA.HH. Nuevo San Lorenzo, San Juan, Iquitos (Peru). Lab. de Investigacion en Productos Naturales Antiparasitarios de la Amazonia

    2011-07-01

    Six pyrrolizidine alkaloids (PAs) (two saturated macrocyclic, three unsaturated macrocyclic and one unsaturated seco-macrocyclic) were isolated from native Peruvian Senecio species. The structures of these alkaloids were established by a complete NMR spectroscopic analysis, chemical transformations and comparison of their NMR data with those published for similar alkaloids. Three PAs were then tested for antifungal activity against Fusarium moniliforme, F. (Sheldon), F. oxysporum fs. lycopersici (Scheldt) and F. solani (Mart), no significant activity being observed. (author)

  8. Synthesis,Charactcrization and Antibacterial Property of Strontium Half and Totally Substituted Hydroxyapatite Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    LIN Yingguang; YANG Zhuoru; CHENG Jiang; WANG Lianshi

    2008-01-01

    Nanoparticles of hydroxyapatite(HAP),strontium half substituted hydroxyapatite(SrCaHAP) and strontium totally substituted hydroxyapatite(SrHAP)were prepared by sol-gel-supercritical fluid drying (SCFD) method.The nanoparticles were characterized by element content analysis,FT-IR,XRD and TEM,and the effects of strontium substitution on crystal structure.crystallinity,particle shape and antibacterial propemes of the nanoparticles on Escherichia coli,Staphylococcus aureus,Lactobacillus were researched.Results show that strontium can half and totally substitute for calcium and enter the structure of apatite according to the initial atomic ratios of Sr/[Sr+Ca] as 0.5,1.The substitution decreases the IR wavenumbers of SrCaHAP and SrHAP, and changes the morphology of the nanoparticles from short rod shaped HAP to needle shaped SrCaHAE and back to short rod shaped SrHAP.The crystallinity of HAP is higher than that of SrCaHAP, but is lower thall that of SrHAP.Moreove~the antibacterial property of SrCaHAP and SrHAP are improved after the calcium is half and totally substituted by strontium.

  9. Efficient Total Chemical Synthesis of (13) C=(18) O Isotopomers of Human Insulin for Isotope-Edited FTIR.

    Science.gov (United States)

    Dhayalan, Balamurugan; Fitzpatrick, Ann; Mandal, Kalyaneswar; Whittaker, Jonathan; Weiss, Michael A; Tokmakoff, Andrei; Kent, Stephen B H

    2016-03-01

    Isotope-edited two-dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site-specific incorporation of stable (13) C=(18) O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis-via a key ester insulin intermediate-of 97 % enriched [(1-(13) C=(18) O)Phe(B24) ] human insulin: stable-isotope labeled at a single backbone amide carbonyl. The amino acid sequence as well as the positions of the disulfide bonds and the correctly folded structure were unambiguously confirmed by the X-ray crystal structure of the synthetic protein molecule. In vitro assays of the isotope labeled [(1-(13) C=(18) O)Phe(B24) ] human insulin showed that it had full insulin receptor binding activity. Linear and 2 D IR spectra revealed a distinct red-shifted amide I carbonyl band peak at 1595 cm(-1) resulting from the (1-(13) C=(18) O)Phe(B24) backbone label. This work illustrates the utility of chemical synthesis to enable the application of advanced physical methods for the elucidation of the molecular basis of protein function. PMID:26715336

  10. A Short Synthetic Route to the Calystegine Alkaloids

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2003-01-01

    An efficient strategy is described for the synthesis of enantiopure calystegine alkaloids. The key step employs a zinc-mediated fragmentation of benzyl-protected methyl 6-iodo-glycosides followed by in situ formation of the benzyl imine and Barbier-type allylation with zinc, magnesium, or indium...... metal. Stereochemistry in the pivotal allylation is controlled by the choice of the metal. The functionalized 1,8-nonadienes, thus formed, are converted into cycloheptenes by ring-closing metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected...

  11. Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

    Directory of Open Access Journals (Sweden)

    Trong D. Tran

    2015-07-01

    Full Text Available Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A–C (1–3, belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A–C (1–3, respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells.

  12. Isolation and Total Synthesis of Stolonines A-C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera.

    Science.gov (United States)

    Tran, Trong D; Pham, Ngoc B; Ekins, Merrick; Hooper, John N A; Quinn, Ronald J

    2015-07-01

    Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A-C (1-3), belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A-C (1-3), respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells. PMID:26204949

  13. Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua.

    Science.gov (United States)

    Tanabe, Genzoh; Sugano, Youta; Shirato, Miki; Sonoda, Naoki; Tsutsui, Nozomi; Morikawa, Toshio; Ninomiya, Kiyofumi; Yoshikawa, Masayuki; Muraoka, Osamu

    2015-07-24

    The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an α,α-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported (13)C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 μM) of 6 was 40 times stronger than that of arbutin (174 μM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds. PMID:26135746

  14. Antimalarial activity of extracts and alkaloids isolated from six plants used in traditional medicine in Mali and Sao Tome.

    Science.gov (United States)

    Ancolio, C; Azas, N; Mahiou, V; Ollivier, E; Di Giorgio, C; Keita, A; Timon-David, P; Balansard, G

    2002-11-01

    Methanol and chloroform extracts were prepared from various parts of four plants collected in Mali: Guiera senegalensis (Gmel.) Combretaceae, Feretia apodanthera (Del.) Rubiaceae, Combretum micranthum (Don.) Combretaceae, Securidaca longepedunculata (Fres.) Polygalaceae and two plants -collected in Sao Tome: Pycnanthus angolensis (Welw.) Myristicaceae and Morinda citrifolia (Benth.) Rubiaceae were assessed for their in vitro antimalarial activity and their cytotoxic effects on human monocytes (THP1 cells) by flow cytometry. The methanol extract of leaves of Feretia apodanthera and the chloroform extract of roots of Guiera senegalensis exhibited a pronounced antimalarial activity. Two alkaloids isolated from the active extract of Guiera senegalensis, harman and tetrahydroharman, showed antimalarial activity (IC(50) lower than 4 microg/mL) and displayed low toxicity against THP1. Moreover, the decrease of THP1 cells in S phase of the cell cycle, after treatment with harman and tetrahydroharman, was probably due to an inhibition of total protein synthesis. PMID:12410545

  15. Total Synthesis of Purported Cephalosporolides H and I, Penisporolide B, and Their Stereoisomers.

    Science.gov (United States)

    Wang, Jian; Tong, Rongbiao

    2016-05-20

    Development of a unified, bioinspired synthetic strategy to access four possible diastereomers of unique 2,2-dimethyl-[5,5]-spiroacetal-cis-fused-γ-lactone (Me2SAFL) is reported, featuring pyridinium chlorochromate (PCC)-promoted oxidative ring expansion of β-hydroxy cyclic ethers and dehydrative ring-contraction rearrangement of 10-membered lactones. Synthetic utility of this strategy was demonstrated by total syntheses of 12 Me2SAFLs, corresponding to the purported cephalosporolide H (CesH), cephalosporolide I (CesI), and penisporolide B (PenB) and their possible diastereomers. Comprehensive NMR data analysis suggested that the tricyclic Me2SAFL core of CesH, CesI, and PenB should be revised to the same relative (3R*, 4R*, 6S*, 9R*) configuration and that the side chains required an unknown constitutional structure revision. PMID:27137949

  16. Total observed organic carbon (TOOC in the atmosphere: a synthesis of North American observations

    Directory of Open Access Journals (Sweden)

    C. L. Heald

    2008-04-01

    Full Text Available Measurements of organic carbon compounds in both the gas and particle phases made upwind, over and downwind of North America are synthesized to examine the total observed organic carbon (TOOC in the atmosphere over this region. These include measurements made aboard the NOAA WP-3 and BAe-146 aircraft, the NOAA research vessel Ronald H. Brown, and at the Thompson Farm and Chebogue Point surface sites during the summer 2004 ICARTT campaign. Both winter and summer 2002 measurements during the Pittsburgh Air Quality Study are also included. Lastly, the spring 2002 observations at Trinidad Head, CA, surface measurements made in March 2006 in Mexico City and coincidentally aboard the C-130 aircraft during the MILAGRO campaign and later during the IMPEX campaign off the northwestern United States are incorporated. Concentrations of TOOC in these datasets span more than two orders of magnitude. The daytime mean TOOC ranges from 4.0 to 456 μgC m−3 from the cleanest site (Trinidad Head to the most polluted (Mexico City. Organic aerosol makes up 3–17% of this mean TOOC, with highest fractions reported over the northeastern United States, where organic aerosol can comprise up to 50% of TOOC. Carbon monoxide concentrations explain 46 to 86% of the variability in TOOC, with highest TOOC/CO slopes in regions with fresh anthropogenic influence, where we also expect the highest degree of mass closure for TOOC. Correlation with isoprene, formaldehyde, methyl vinyl ketone and methacrolein also indicates that biogenic activity contributes substantially to the variability of TOOC, yet these tracers of biogenic oxidation sources do not explain the variability in organic aerosol observed over North America. We highlight the critical need to develop measurement techniques to routinely detect total gas phase VOCs, and to deploy comprehensive suites of TOOC instruments in diverse environments to quantify the ambient evolution of organic carbon from source

  17. Total Observed Organic Carbon (TOOC: A synthesis of North American observations

    Directory of Open Access Journals (Sweden)

    C. L. Heald

    2007-12-01

    Full Text Available Measurements of organic carbon compounds in both the gas and particle phases measured upwind, over and downwind of North America are synthesized to examine the total observed organic carbon (TOOC over this region. These include measurements made aboard the NOAA WP-3 and BAe-146 aircraft, the NOAA research vessel Ronald H. Brown, and at the Thompson Farm and Chebogue Point surface sites during the summer 2004 ICARTT campaign. Both winter and summer 2002 measurements during the Pittsburgh Air Quality Study are also included. Lastly, the spring 2002 observations at Trinidad Head, CA, surface measurements made in March 2006 in Mexico City and coincidentally aboard the C-130 aircraft during the MILAGRO campaign and later during the IMPEX campaign off the northwestern United States are incorporated. Concentrations of TOOC in these datasets span more than two orders of magnitude. The daytime mean TOOC ranges from 4.0 to 456 μgC m−3 from the cleanest site (Trinidad Head to the most polluted (Mexico City. Organic aerosol makes up 3–17% of this mean TOOC, with highest fractions reported over the northeastern United States, where organic aerosol can comprise up to 50% of TOOC. Carbon monoxide concentrations explain 46 to 86% of the variability in TOOC, with highest TOOC/CO slopes in regions with fresh anthropogenic influence, where we also expect the highest degree of mass closure for TOOC. Correlation with isoprene, formaldehyde, methyl vinyl ketene and methacrolein also indicates that biogenic activity contributes substantially to the variability of TOOC, yet these tracers of biogenic oxidation sources do not explain the variability in organic aerosol observed over North America. We highlight the critical need to develop measurement techniques to routinely detect total gas phase VOCs, and to deploy comprehensive suites of TOOC instruments in diverse environments to quantify the ambient evolution of organic carbon from source to sink.

  18. Total Observed Organic Carbon (TOOC): A Synthesis of North American Observations

    Science.gov (United States)

    Heald, C. L.; Goldstein, A. H.; Allan, J. D.; Aiken, A. C.; Apel, E.; Atlas, E. L.; Baker, A. K.; Bates, T. S.; Beyersdorf, A. J.; Blake, D. R.; Campos, T.; Coe, H.; Crounse, J. D.; DeCarlo, P. F.; de Gouw, J. A.; Dunlea, E. J.; Flocke, F. M.; Fried, A.; Goldan, P.; Griffin, R. J.; Herndon, S. C.; Holloway, J. S.; Holzinger, R.; Jimenez, J. L.; Junkermann, W.

    2007-01-01

    Measurements of organic carbon compounds in both the gas and particle phases made upwind, over and downwind of North America are synthesized to examine the total observed organic carbon (TOOC) in the atmosphere over this region. These include measurements made aboard the NOAA WP-3 and BAe-146 aircraft, the NOAA research vessel Ronald H. Brown, and at the Thompson Farm and Chebogue Point surface sites during the summer 2004 ICARTT campaign. Both winter and summer 2002 measurements during the Pittsburgh Air Quality Study are also included. Lastly, the spring 2002 observations at Trinidad Head, CA, surface measurements made in March 2006 in Mexico City and coincidentally aboard the C-130 aircraft during the MILAGRO campaign and later during the IMPEX campaign off the northwestern United States are incorporated. Concentrations of TOOC in these datasets span more than two orders of magnitude. The daytime mean TOOC ranges from 4.0 to 456 microg C/cubic m from the cleanest site (Trinidad Head) to the most polluted (Mexico City). Organic aerosol makes up 3-17% of this mean TOOC, with highest fractions reported over the northeastern United States, where organic aerosol can comprise up to 50% of TOOC. Carbon monoxide concentrations explain 46 to 86% of the variability in TOOC, with highest TOOC/CO slopes in regions with fresh anthropogenic influence, where we also expect the highest degree of mass closure for TOOC. Correlation with isoprene, formaldehyde, methyl vinyl ketone and methacrolein also indicates that biogenic activity contributes substantially to the variability of TOOC, yet these tracers of biogenic oxidation sources do not explain the variability in organic aerosol observed over North America. We highlight the critical need to develop measurement techniques to routinely detect total gas phase VOCs, and to deploy comprehensive suites of TOOC instruments in diverse environments to quantify the ambient evolution of organic carbon from source to sink.

  19. Multiple shoot cultures of Atropa belladonna: Effect of physico-chemical factors on growth and alkaloid formation

    International Nuclear Information System (INIS)

    Multiple shoot cultures were established from shoot tip and axillary meristem of the plant Atropa belladonna. The cultures were initially raised on agar medium and subsequently maintained on liquid medium of Murashige and Skoog (1962) supplemented with BA. These cultures were subjected to different doses of -y-irradiation. Recovery from the radiation effects was observed in tissues subjected to 29 Gy during four successive passages. Plant growth regulators influenced the growth and morphogenetic events of the tissues. The precursors of tropane alkaloids marginally increased the alkaloid synthesis during the stationary phase of growth. Shoot cultures, established from different field grown plants varying in alkaloid content, were morphologically similar and did not exhibit the parental characteristics with respect to alkaloid formation

  20. Halogenated indole alkaloids from marine invertebrates.

    Science.gov (United States)

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade E; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  1. Halogenated Indole Alkaloids from Marine Invertebrates

    Directory of Open Access Journals (Sweden)

    Ana Helena Januário

    2010-04-01

    Full Text Available This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins, as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided.

  2. Halogenated Indole Alkaloids from Marine Invertebrates

    OpenAIRE

    Ana Helena Januário; Wilson Roberto Cunha; Márcio Luís Andrade e Silva; Ademar Alves da Silva Filho; Caio Guedes Braguine; Lucas Silva Cintra; Patrícia Mendonça Pauletti

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided.

  3. An integrated strategy for the systematic characterization and discovery of new indole alkaloids from Uncaria rhynchophylla by UHPLC/DAD/LTQ-Orbitrap-MS.

    Science.gov (United States)

    Pan, Huiqin; Yang, Wenzhi; Zhang, Yibei; Yang, Min; Feng, Ruihong; Wu, Wanying; Guo, Dean

    2015-08-01

    The exploration of new chemical entities from herbal medicines may provide candidates for the in silico screening of drug leads. However, this significant work is hindered by the presence of multiple classes of plant metabolites and many re-discovered structures. This study presents an integrated strategy that uses ultrahigh-performance liquid chromatography/linear ion-trap quadrupole/Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS) coupled with in-house library data for the systematic characterization and discovery of new potentially bioactive molecules. Exploration of the indole alkaloids from Uncaria rhynchophylla (UR) is presented as a model study. Initially, the primary characterization of alkaloids was achieved using mass defect filtering and neutral loss filtering. Subsequently, phytochemical isolation obtained 14 alkaloid compounds as reference standards, including a new one identified as 16,17-dihydro-O-demethylhirsuteine by NMR analyses. The direct-infusion fragmentation behaviors of these isolated alkaloids were studied to provide diagnostic structural information facilitating the rapid differentiation and characterization of four different alkaloid subtypes. Ultimately, after combining the experimental results with a survey of an in-house library containing 129 alkaloids isolated from the Uncaria genus, a total of 92 alkaloids (60 free alkaloids and 32 alkaloid O-glycosides) were identified or tentatively characterized, 56 of which are potential new alkaloids for the Uncaria genus. Hydroxylation on ring A, broad variations in the C-15 side chain, new N-oxides, and numerous O-glycosides, represent the novel features of the newly discovered indole alkaloid structures. These results greatly expand our knowledge of UR chemistry and are useful for the computational screening of potentially bioactive molecules from indole alkaloids. Graphical Abstract A four-step integrated strategy for the systematic characterization and efficient discovery of new indole

  4. Iboga-Type Alkaloids from Ervatamia officinalis.

    Science.gov (United States)

    Tang, Ben-Qin; Wang, Wen-Jing; Huang, Xiao-Jun; Li, Guo-Qiang; Wang, Lei; Jiang, Ren-Wang; Yang, Ting-Ting; Shi, Lei; Zhang, Xiao-Qi; Ye, Wen-Cai

    2014-08-22

    Seven new iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed. PMID:25093992

  5. Staphylococcal enterotoxin A gene-carrying Staphylococcus aureus isolated from foods and its control by crude alkaloid from papaya leaves.

    Science.gov (United States)

    Handayani, Lita; Faridah, Didah Nur; Kusumaningrum, Harsi D

    2014-11-01

    Staphylococcus aureus is a known pathogen causing intoxication by producing enterotoxins in food. Staphylococcal enterotoxin A is one of the enterotoxins commonly implicated in staphylococcal food poisoning. The ability of crude alkaloid extract from papaya leaves to inhibit the growth of S. aureus and staphylococcal enterotoxin A synthesis was investigated. Staphylococcal enterotoxin A gene-carrying S. aureus was isolated from raw milk and ready-to-eat foods. Crude alkaloid was extracted from ground, dried papaya leaves using ultrasonic-assisted extraction, and a MIC of the alkaloid was determined by the broth macrodilution method. Furthermore, S. aureus isolate was exposed to the crude alkaloid extract at one- and twofold MIC, and the expression of sea was subsequently analyzed using a quantitative reverse transcription real-time PCR. Ten isolates of S. aureus were obtained, and nine of those isolates were sea carriers. The yield of crude alkaloid extract was 0.48 to 1.82% per dry weight of papaya leaves. A MIC of crude alkaloid to S. aureus was 0.25 mg/ml. After exposure to the alkaloid at 0.25 and 0.5 mg/ml for 2 h, a significant increase in cycle threshold values of sea was observed. The sea was expressed 29 and 41 times less when S. aureus was exposed to crude alkaloid at one- and twofold MIC, respectively. This study revealed that crude alkaloid of papaya leaves could control staphylococcal enterotoxin A gene-carrying S. aureus by suppressing the expression of sea, in addition to the ability to inhibit the growth of S. aureus. The expression of sea was successfully quantified. PMID:25364936

  6. Bis and tris indole alkaloids from marine organisms: new leads for drug discovery.

    Science.gov (United States)

    Gupta, Leena; Talwar, Archna; Chauhan, Prem M S

    2007-01-01

    The marine organisms are a rich source of varied natural products with unique functionality. Marine natural products chemistry has undergone an explosive growth during the past three decades. A variety of natural products of new molecular structures with diverse biological activities have been reported from marine flora and fauna, thus ensuring motivation in the search of newer natural products. The bis and trisindole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. 3-hydroxy staurosporine 51, an indolo carbazole having powerful antiproliferative activity. Hamacanthin A 1 and B 2, pyrazinone alkaloids have significant antimicrobial activity. Coscinamides 60-62 and Chondriamides 63-65 an indolic enamides which have anti-HIV and cytotoxic activity respectively. Gelluisine A 66 and B 67, trisindole alkaloids have strong anti-serotonin activity and strong affinity with somatostatin and neuropeptide Y receptors in receptor-binding assays. This report reviews the literature on these alkaloids of marine origin and highlights the isolation, structure, latest synthesis and specific biological activities including cytotoxicity, antiviral, antiparasitic, serotonin antagonism and other pharmacological activities of sixty-nine bis and trisindole alkaloids. PMID:17627517

  7. Effect of total alkaloidal of tongbiling on cartilage and cellular metabolism in rats with collagen-induced arthritis%通痹灵总碱对胶原诱导型关节炎大鼠软骨及其细胞代谢的影响

    Institute of Scientific and Technical Information of China (English)

    陈纪藩; 赵诗哲; 陈光星; 刘清平; 陈宗良

    2005-01-01

    ,10,100,500,1 000μg/L)促进了软骨细胞蛋白多糖的降解(P<0.01),且呈量效关系.③不同浓度的通痹灵总碱(200,100,50,25 mg/L)及地塞米松可明显抑制软骨细胞蛋白多糖的降解(P<0.01)及一氧化氮的产生(P<0.01).结论:通痹灵总碱可抑制胶原诱导型关节炎大鼠趾关节软骨破坏;体外实验结果显示通痹灵总碱可对抗软骨细胞蛋白多糖的降解,其作用途径可能是通过抑制一氧化氮的生成来实现的.%BACKGROUND: Chinese medicine is rich in recognition and treatment for rheumatoid arthritis(RA) and has achieved attractable progression in researches of recent several years,characterized by variable therapeutic methods, definite therapeutic effects and few toxic side effects. Therefore, it is important scientifically and socially to further search for the effective drugs and methods for the treatment of RA in the field of Chinese medicine. There are few reports on whether Chinese herbs inhibit or block the destruction of cartilage and bone and promote their metabolism and repair for damage or not by variable approaches,targets and links in RA occurrence.OBJECTIVE: To probe into the mechanism of Chinese herbal tongbiling on cartilage destruction.DESIGN: Complete random design and control experimental study based on the experimental animals.SETTING: Golden Chamber teaching and research room of guangzhou university of traditional Chinese medicine.MATERIALS: The experiment was performed in Comprehensive Experimental Room of First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from August 2002 to December 2003,in which,35female Wistar rats were employed,clean grade,weighted(110±20) g,provided by Animal Experimental Room of First Military Medical University of Chinese PLA, with qualified animal No. 2002A041.After 3 days adaptive breeding,Wistar rats were randomized into normal group,model group and total alkaloidal of tongbiling group(TBL group). TBL was extracted in

  8. Total synthesis of cis-hydroazulene sesquiterpenes. Base-induced and -directed elimination and rearrangement reactions of perhydronaphthalene-1,4-diol monosulfonate esters.

    NARCIS (Netherlands)

    Jenniskens, L.H.D.

    1992-01-01

    The total synthesis of a number of cis-fused hydroazulene sesquiterpenes is described in this thesis. In this synthetic study, ample attention is paid to the mechanistic aspects of the base- induced and -directed rearrangement and elimination reactions of perhydronaphthalene-1,4-diol monosulfonate e

  9. Enantioselective total synthesis of bioactive natural product (+)-Sch642305: a structurally novel inhibitor of bacterial DNA primase and HIV-1 Tat transactivation

    OpenAIRE

    Mehta, Goverdhan; Shinde, Harish M

    2005-01-01

    The total synthesis of the bioactive natural product (+)-Sch 642305 has been achieved from a readily available chiral building block using an RCM protocol to construct the key decalactone moiety; our approach is notable for its built-in flexibility and is diversity oriented.

  10. Enantioselective total synthesis of epoxyquinone natural products (−)-phyllostine, (+)-epoxydon, (+)-epiepoxydon and (−)-panepophenanthrin: access to versatile chiral building blocks through enzymatic kinetic resolution

    OpenAIRE

    Mehta, Goverdhan; Islam, Kabirul

    2004-01-01

    A new enzyme mediated protocol to access versatile chiral building blocks for the synthesis of epoxyquinone natural products is delineated. Total syntheses of (−)-phyllostine, (+)-epoxydon, (+)-epiepoxydon and (−)-panepophenanthrin have been accomplished to demonstrate the efficacy of this approach.

  11. Asymmetric Total Synthesis of (+)- and (−)-Clusianone and (+)- and (−)Clusianone Methyl Enol Ether via ACC Alkylation and Evaluation of their Anti-HIV Activity

    OpenAIRE

    Garnsey, Michelle R.; Matous, James A.; Kwiek, Jesse J; Coltart, Don M.

    2011-01-01

    The total asymmetric synthesis of (+)- and (−)-clusianone and (+)- and (−)-clusianone methyl enol ether is reported. Asymmetric induction is achieved through the use of ACC alkylation, providing the key intermediates with an er of 99:1. The four synthetic compounds were evaluated for their anti-HIV activity. Both (+)- and (−)-clusianone displayed significant anti-HIV activity.

  12. Short-term toxicity studies of loline alkaloids in mice.

    Science.gov (United States)

    Finch, S C; Munday, J S; Munday, R; Kerby, J W F

    2016-08-01

    Epichloë endophytes have been used successfully in pastoral systems to reduce the impact of insect pests through the expression of secondary metabolites. The use of endophytes could be extended to other plant species, such as cereal crops, where the production of bioactive secondary metabolites would reduce the reliance on pesticides for insect control. The success of this approach is dependent on the selection of an appropriate secondary metabolite target which must not only be effective against insect pests but also be safe for grazing and monogastric animals. The loline alkaloids have been identified as possible target metabolites as they are associated with potent effects on insects and low toxicity to grazing animals. The purpose of the current study was to generate toxicological data on the loline alkaloids in a monogastric system using mice. Male and female mice were fed 415 mg/kg/day total lolines for a 3-week period. The loline treatment caused no statistically significant effect on gross pathology, histology, haematology, blood chemistry, heart rate, blood pressure or motor coordination. Reduced weight gain and food consumption were noted in the loline groups during the initial stages of the experiment. This experiment raises no food safety concerns for the loline alkaloids. PMID:27276360

  13. Relationships among Ergot Alkaloids, Cytochrome P450 Activity, and Beef Steer Growth

    Science.gov (United States)

    Rosenkrans, Charles; Ezell, Nicholas

    2015-03-01

    Determining a grazing animal’s susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 μM of ergotamine (ET), dihydroergotamine (DHET), and ergonovine (EN)] on human CYP3A4 using the P450-Glo assay (Promega™ V9800). With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 d of age; 203 ± 1.7 kg) after grazing tall fescue pastures for 105 d. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control). Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7) was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = -0.31; P animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins.

  14. Bioactive acridone alkaloids from Swinglea glutinosa.

    Science.gov (United States)

    Weniger, B; Um, B H; Valentin, A; Estrada, A; Lobstein, A; Anton, R; Maillé, M; Sauvain, M

    2001-09-01

    A new prenylated acridone alkaloid, 1,3,5-trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone (1), was isolated from the stembark of Swinglea glutinosa, along with three known acridone alkaloids, 5-hydroxynoracronycine (2), 1,3,5-trihydroxy-4-methoxy-2-(3-methylbut-2-enyl)-10-methyl-9-acridone (3), and 1,3,5-trihydroxy-4-methoxy-10-methylacridone (4). The isolated alkaloids were assessed in vitro against chloroquine-sensitive and -resistant Plasmodium falciparum strains and for cytotoxicity using HeLa cells. PMID:11575960

  15. 半夏总生物碱对帕金森病大鼠学习记忆功能的影响及其机制的初步探讨%Effect of total alkaloid derived from Pinellia ternata on learning and memory and preliminary study of its mechanism in rats with Parkinson disease

    Institute of Scientific and Technical Information of China (English)

    周芳; 刁波; 段凯; 范圳涛; 张宜

    2011-01-01

    Objective To observe the effect of total alkaloid derived from Pinellia ternata on learning and memory and to study its mechanism in the rats with Parkinson disease (PD).Methods Fifty male rats were randomly divided into 5 groups of 10 animals each including normal group(A), control group(B), high dose treatment group(C), moderate dose treatment group(D) and low dose treatment group(E).The corresponding dose of total alkaloid derived from Pinellia ternate was infused into the animal stomach once every day for 8 weeks in all the treatment groups.The animal model of PD was established by subcutaneous injection of 1-methyl-4-phenyl-1, 2, 3,6-tetrahydropyridine (MPTP).The learning and memory were determined by water maze test in all the groups.The expressions of heat shock protein 70 (HSP70) and HSP70 mRNA in the substantia nigra were determined respectively by immunohistochemical technique and RT-PCR technique in all groups.Results The escape latency (EL) in groups A~E was (14.5± 1.05)s, (26.4±2.87)s, (19.8±3.31)s,(21.6±2.24)s and (25.5±4.48)s respectively.The levels of HSP70 expressions in groups A~E were (25.5±3.47) positive unit (PU), (27.4±5.82)PU, (42.3±5.27)PU, (35.4±6.8)PU and (29.6±4.97)PU respectively.The levels of HSP70 mRAN expressions in groups A~E were 0.4572±0.031, 0.5082±0.064, 0.6237±0.028, 0.5745 ±0.042 and 0.5181 ±0.055 respectively.EL was significantly shorter in groups A,C,and D.The levels of HSP70 and HSP70 mRNA expressions were significantly higher in groups C and D than those in group B (P<0.05).Conclusion The learning and memory may be improved by the total alkaloid derived from Pinellia ternate, by which upregulation of HSP70 expression in the suhstatia nigra may be related to improving the learning and memory in the rats with PD.%目的 观察半夏总生物碱对帕金森病(PD)大鼠学习记忆功能的影响并初步探讨其机制.方法 将50只清洁级级雄性Wistar大鼠随机分为五组,即正常组(A)、

  16. 杀结核菌素的全合成研究%An Improved Total Synthesis of Tubercidin

    Institute of Scientific and Technical Information of China (English)

    黄海洋; 阮志忠; 胡韬; 肖强

    2014-01-01

    Tubercidin is a naturally occurring pyrrolo[2,3-d]pyrimidine nucleoside with significantly biological activities, such as anti-schistosomal, antibacterial and antitumor. An improved total synthesis of tubercidin is reported using microwave promoted Vorbrüggen glycosylation as the key step. Thus, tubercidin was synthesized in 3 steps with 74%overal yield using 6-chloro-7-bromo-pyrrolo[2,3-d]pyrimidine and 1-O-acetyl-2,3,5-O-tribenzoyl-β-D-ribose as starting materials. The applica-tion of micromave irridated one-pot reaction is also reported in the synthesis of 7-deazapurine nucleosides using potassium nonafluoro-1-butanesulfonate, trimethylsilyl chloride and silylation reagent [hexamethyldisilazane or N,O-bis(trimethyl-silyl)acetamide].%杀结核菌素是一个吡咯[2,3-d]嘧啶核苷天然产物,具有显著的抗血吸虫感染、抗菌和抗肿瘤活性。报道了以微波促进的Vorbrüggen糖基化反应为关键步骤,以6-氯-7-溴-吡咯[2,3-d]嘧啶和1-O-乙酰基-2,3,5-O-三苯甲酰基-β-D-呋喃核糖为原料,经过3步反应以74%的总收率完成了杀结核菌素的全合成。同时研究了以全氟丁基磺酸钾、三甲基氯硅烷和硅基化试剂[六甲基二硅胺烷或者N,O-双(三甲基硅基)乙酰胺]在微波加热下一锅法合成7-去氮嘌呤核苷的方法。

  17. Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (Rubiaceae family) leaves.

    Science.gov (United States)

    Parthasarathy, Suhanya; Bin Azizi, Juzaili; Ramanathan, Surash; Ismail, Sabariah; Sasidharan, Sreenivasan; Said, Mohd I Mohd; Mansor, Sharif Mahsufi

    2009-01-01

    Studies on the antioxidant and antimicrobial activities of Mitragyna speciosa leaf extracts are lacking. In this study the antioxidant properties of water, methanolic and alkaloid M. speciosa leaf extracts were evaluated using the DPPH (2,2-diphenyl-1- picrylhydrazyl) radical scavenging method. The amount of total phenolics and flavanoid contents were also estimated. The DPPH IC(50) values of the aqueous, alkaloid and methanolic extracts were 213.4, 104.81 and 37.08 microg/mL, respectively. The total phenolic content of the aqueous, alkaloid and methanolic extracts were 66.0 mg, 88.4, 105.6 mg GAE/g, respectively, while the total flavanoid were 28.2, 20.0 and 91.1 mg CAE/g respectively. The antioxidant activities were correlated with the total phenolic content. This result suggests that the relatively high antioxidant activity of the methanolic extract compared to aqueous and alkaloid extract could be possibly be due to its high phenolic content. The aqueous, alkaloid and methanolic extracts were screened for antimicrobial activity. The extracts showed antimicrobial activity against Salmonella typhi and Bacillus subtilis. The minimum inhibitory concentrations (MICs) of extracts determined by the broth dilution method ranged from 3.12 to 6.25 mg/mL. The alkaloid extract was found to be most effective against all of the tested organisms. PMID:19924042

  18. Evaluation of Antioxidant and Antibacterial Activities of Aqueous, Methanolic and Alkaloid Extracts from Mitragyna Speciosa (Rubiaceae Family Leaves

    Directory of Open Access Journals (Sweden)

    Mohd I. Mohd. Said

    2009-10-01

    Full Text Available Studies on the antioxidant and antimicrobial activities of Mitragyna speciosa leaf extracts are lacking. In this study the antioxidant properties of water, methanolic and alkaloid M. speciosa leaf extracts were evaluated using the DPPH (2,2-diphenyl-1- picrylhydrazyl radical scavenging method. The amount of total phenolics and flavanoid contents were also estimated. The DPPH IC50 values of the aqueous, alkaloid and methanolic extracts were 213.4, 104.81 and 37.08 μg/mL, respectively. The total phenolic content of the aqueous, alkaloid and methanolic extracts were 66.0 mg, 88.4, 105.6 mg GAE/g, respectively, while the total flavanoid were 28.2, 20.0 and 91.1 mg CAE/g respectively. The antioxidant activities were correlated with the total phenolic content. This result suggests that the relatively high antioxidant activity of the methanolic extract compared to aqueous and alkaloid extract could be possibly be due to its high phenolic content. The aqueous, alkaloid and methanolic extracts were screened for antimicrobial activity. The extracts showed antimicrobial activity against Salmonella typhi and Bacillus subtilis. The minimum inhibitory concentrations (MICs of extracts determined by the broth dilution method ranged from 3.12 to 6.25 mg/mL. The alkaloid extract was found to be most effective against all of the tested organisms.

  19. Main Alkaloids of Peganum harmala L. and Their Different Effects on Dicot and Monocot Crops

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2013-02-01

    Full Text Available Alkaloids with allelopathic activity are not as well-known as other allelochemicals. Our study revealed that total alkaloids from seeds of the medicinal plant Peganum harmala L. possessed significant growth inhibitory effect on four treated plants, with dicot plants (lettuce and amaranth being more sensitive than the tested monocot plants (wheat and ryegrass. Further investigation led to the isolation of harmaline and harmine as the main active ingredients in the total alkaloids of P. harmala seeds. Harmaline exerted potent inhibitory effects on seedling growth of treated plants, especially dicots, inhibiting root elongation of lettuce and amaranth by 31% and 47% at a very low concentration (5 µg/mL, whereas harmine exhibited much weaker non-selective inhibitory effect on the plants. Considering the high yield and poor utilization of P. harmala in China, we anticipate that this plant could be exploited as an alternative weed management tool in the future.

  20. Optimization of Extraction and Enrichment of Steroidal Alkaloids from Bulbs of Cultivated Fritillaria cirrhosa

    Directory of Open Access Journals (Sweden)

    Dongdong Wang

    2014-01-01

    Full Text Available The bulbs of cultivated Fritillaria cirrhosa (BCFC are used in China both for food and folk medicine due to its powerful biological activities. The aim of this study is to optimize the extraction and enrichment conditions of alkaloids from BCFC. Firstly, the orthogonal experimental design was used to optimize and evaluate four variables (ethanol concentration, solid-liquid ratio, extraction time, and temperature. Thereafter, resin adsorption was as a means to enrich alkaloids. Among 16 tested resins, H-103 resin presented higher adsorption capacity and desorption ratio. The equilibrium experimental data of the adsorption of total alkaloids, imperialine, and peimisine were well-fitted to the pseudo-first-order kinetics model, Langmuir and Freundlich isotherms models. Finally, in order to optimize the parameters for purifying alkaloids, dynamic adsorption and desorption tests were carried out. After one run treatment with H-103 resin, the contents of total alkaloids, imperialine, and peimisine in the product were 21.40-, 18.31-, and 22.88-fold increased with recovery yields of 94.43%, 90.57%, and 96.16%, respectively.

  1. Total syntheses of hyperforin and papuaforins A-C, and formal synthesis of nemorosone through a gold(I)-catalyzed carbocyclization.

    Science.gov (United States)

    Bellavance, Gabriel; Barriault, Louis

    2014-06-23

    The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly decorated bicyclo[3.3.1]nonane-2,4,9-trione frameworks have inspired synthetic organic chemists over the last decade. The concise total syntheses of four natural products PPAPs; hyperforin and papuaforins A-C, and the formal synthesis of nemorosone are reported. Key to the realization of this strategy is the short and scalable synthesis of densely substituted PPAP scaffolds through a gold(I)-catalyzed 6-endo-dig carbocyclization of cyclic enol ethers for late-stage functionalization. PMID:24838522

  2. A novel approach to quinazoline alkaloids

    Czech Academy of Sciences Publication Activity Database

    Chmela, Václav; Amatov, Tynchtyk; Jahn, Ullrich

    Praha: Czech Chemical Society, 2015. s. 82. [Liblice 2015. Advances in Organic , Bioorganic and Pharmaceutical Chemistry /50./. 06.11.2015-08.11.2015, Olomouc] Institutional support: RVO:61388963 Keywords : quinazoline * alkaloids Subject RIV: CC - Organic Chemistry

  3. In vitro anticholinesterase activity of various alkaloids.

    Science.gov (United States)

    Orhan, Ilkay; Naz, Qamar; Kartal, Murat; Tosun, Fatma; Sener, Bilge; Choudhary, M Iqbal

    2007-01-01

    In the current study, a number of alkaloids including retamine, cytisine, and sparteine (quinolizidine-type), yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type) were tested in vitro for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 1 mg/ml concentration by the Ellman method using an ELISA microplate reader. Among the alkaloids tested, only capsaicin exerted a remarkable inhibitory effect towards both AChE and BChE [(62.7 +/- 0.79)% and (75.3 +/- 0.98)%, respectively]. While the rest of the alkaloids did not show any significant inhibition against AChE, three of the alkaloids, namely retamine, sparteine, and yohimbine, exerted a noteworthy anti-BChE effect as compared to galanthamine, the reference drug. PMID:18069241

  4. A novel alkaloid from Gaultheria nummularioides.

    Science.gov (United States)

    Yang, M-F; Li, Y-Y; Li, B-G; Zhang, G-L

    2007-03-01

    A novel alkaloid, gaultherialine A (1), along with twenty-seven known compounds were isolated from the whole plants of Gaultheria nummularioides D. Don. The structure of the new alkaloid was elucidated as 7,8-dimethoxy-1-(4-methoxyphenyl)-4,5-dihydro-2H-benzo[e]indole-2-one N-oxide (1) on the basis of spectral evidence. PMID:17454316

  5. Alkaloids from Fissistigma latifolium (Dunal) Merr.

    OpenAIRE

    Asmah Alias; Hazrina Hazni; Faridahanim Mohd Jaafar; Khalijah Awang; Nor Hadiani Ismail

    2010-01-01

    A phytochemical study of the bark of Fissistigma latifolium (Annonaceae) yielded a new aporphine alkaloid, (-)-N-methylguattescidine (1), and eight known alkaloids: liriodenine (2), oxoxylopine (3), (-)-asimilobine (4), dimethyltryptamine (5), (-)-remerine (6), (-)-anonaine (7), columbamine (8) and lysicamine (9). The compounds were isolated using various chromatographic methods and structural elucidation was accomplished by means of spectroscopic methods, notably 1D-NMR (1H, 13C, DEPT), 2D-N...

  6. Alkaloids from Fissistigma latifolium (Dunal Merr.

    Directory of Open Access Journals (Sweden)

    Asmah Alias

    2010-06-01

    Full Text Available A phytochemical study of the bark of Fissistigma latifolium (Annonaceae yielded a new aporphine alkaloid, (--N-methylguattescidine (1, and eight known alkaloids: liriodenine (2, oxoxylopine (3, (--asimilobine (4, dimethyltryptamine (5, (--remerine (6, (--anonaine (7, columbamine (8 and lysicamine (9. The compounds were isolated using various chromatographic methods and structural elucidation was accomplished by means of spectroscopic methods, notably 1D-NMR (1H, 13C, DEPT, 2D-NMR (COSY, HMQC, HMBC, UV, IR and MS.

  7. Ether bridge formation in loline alkaloid biosynthesis

    OpenAIRE

    Pan, Juan; Bhardwaj, Minakshi; Faulkner, Jerome R.; Nagabhyru, Padmaja; Charlton, Nikki D.; Higashi, Richard M.; Miller, Anne-Frances; Young, Carolyn A; Grossman, Robert B.; Schardl, Christopher L

    2013-01-01

    Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of a novel alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes...

  8. Seco-tabersonine alkaloids from Tabernaemontana corymbosa.

    Science.gov (United States)

    Lim, Kuan-Hon; Thomas, Noel F; Abdullah, Zanariah; Kam, Toh-Seok

    2009-02-01

    Two seco-tabersonine alkaloids, jerantiphyllines A and B, in addition to a tabersonine hydroxyindolenine, jerantinine H, and a recently reported vincamine alkaloid 7, were isolated from the leaf extract of the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis. Biomimetic conversion of jerantinines A and E to their respective vincamine and 16-epivincamine derivatives were also carried out. PMID:19217125

  9. A totally phosphine-free synthesis of metal telluride nanocrystals by employing alkylamides to replace alkylphosphines for preparing highly reactive tellurium precursors.

    Science.gov (United States)

    Yao, Dong; Liu, Yi; Zhao, Wujun; Wei, Haotong; Luo, Xintao; Wu, Zhennan; Dong, Chunwei; Zhang, Hao; Yang, Bai

    2013-10-21

    Despite the developments in the wet chemical synthesis of high-quality semiconductor nanocrystals (NCs) with diverse elemental compositions, telluride NCs are still irreplaceable materials owing to their excellent photovoltaic and thermoelectric performances. Herein we demonstrate the dissolution of elemental tellurium (Te) in a series of alkylamides by sodium borohydride (NaBH4) reduction at relatively low temperature to produce highly reactive precursors for hot-injection synthesis of telluride NCs. The capability to tune the reactivity of Te precursors by selecting injection temperature permits control of NC size over a broad range. The current preparation of Te precursors is simple, economical, and totally phosphine-free, which will promote the commercial synthesis and applications of telluride NCs. PMID:24056800

  10. Total Synthesis of Laulimalide: Assembly of the Fragments and Completion of the Synthesis of the Natural Product and a Potent Analogue

    OpenAIRE

    Trost, Barry M.; Amans, Dominique; Seganish, W. Michael; Chung, Cheol K.

    2012-01-01

    In this manuscript, we report the full account of our efforts to couple the northern and the southern building blocks, whose synthesis were described in the preceding paper, along with the modifications required which ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle followed by a highly stereoselective 1,3-allylic isomerization promot...

  11. Synthesis of unusual alpha-amino acids and study of the effect of their incorporation into antimicrobial peptides. Total synthesis of biactive marine natural products and analogues thereof

    OpenAIRE

    El Marrouni El Ghazaoui, Abdellatif

    2012-01-01

    The principle theme of this thesis was the synthesis of bioactive compounds. To this end, this work was focus on two main projects. The first one, which was carried out in the Department of Chemistry of the University of Girona under the supervision of Dr Montserrat Heras, concerned the synthesis of new unnatural amino acids bearing a pyrimidine ring within their side chain for incorporation into the antimicrobial peptide BP100 following a rational design in order to improve its biological pr...

  12. Total Synthesis of Natural (–)- and ent-(+)-4-Desacetoxy-6,7-dihydrovindorosine and Natural and ent-Minovine: Oxadiazole Tandem Intramolecular Diels–Alder/1,3-Dipolar Cycloaddition Reaction

    OpenAIRE

    Yuan, ZhongQing; Ishikawa, Hayato; Boger, Dale L.

    2005-01-01

    Efficient and unusually concise total syntheses of both enantiomers of the Aspidosperma alkaloids 4-desacetoxy-6,7-dihydrovindorosine (12) and minovine (1) are detailed. A tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reaction of the 1,3,4-oxadiazole 8, in which three new rings, four new C–C bonds and five stereocenters are formed, is a key step in the sequence. The availability of optically active material permitted an assessment of the enantiomeric integrity of minovine and th...

  13. Scientific Opinion on Ergot alkaloids in food and feed

    OpenAIRE

    EFSA Panel on Contaminants in the Food Chain (CONTAM)

    2012-01-01

    The European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on ergot alkaloids (EAs) in food and feed. EAs are produced by several members within the fungal orders of Hypocreales and Eurotiales. In Europe, Claviceps purpurea is the most widespread Claviceps species within the Hypocreales. A total of 20 558 analytical results for EAs in 1 716 food, 496 feed and 67 unprocessed grain samples wer...

  14. Synthesis of Heterocyclic Ring Systems Using Organometallic Reagents

    Institute of Scientific and Technical Information of China (English)

    Sameer Agarwal; Jan Kn(o)ll; Micha P. Krahl; Hans-Joachim Kn(o)lker

    2005-01-01

    @@ 1Introduction We developed novel synthetic routes to heterocyclic ring systems by using transition metal-mediated or -catalyzed reactions. A Lewis acid-promoted addition of the propargyl Grignard reagent 2 to the Schiff base 1 followed by a silvermediated oxidative cyclization of the homopropargylamine 3 provided the aryl-substituted pyrrole 4. Combined with a chemoselective hydrogenation of the pyrrole ring, this method has been applied to the total synthesis of the biologically active fused indolizidine alkaloids ( ± )-harmicine and ( ± )-crispine A[1]. See Fig. 1.

  15. Qualitative and quantitative analyses of alkaloids in Uncaria species by UPLC-ESI-Q-TOF/MS.

    Science.gov (United States)

    Wang, Hai-Bo; Qi, Wen; Zhang, Lin; Yuan, Dan

    2014-01-01

    An ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF/MS) method has been optimized and established for the rapid analysis of the alkaloids in 22 samples originating from five Uncaria (U.) species. The accurate mass measurement of all the protonated molecules and subsequent fragment ions offers higher quality structural information for the interpretation of fragmentation pathways of the various groups of alkaloids. A total of 19 oxindole alkaloids, 16 indole alkaloids and 1 flavone were identified by co-chromatography of the sample extract with authentic standards, comparison of the retention time, characteristic molecular ions and fragment ions, or were tentatively identified by MS/MS determination. Moreover, the method was validated for the simultaneous quantification of the 24 components within 10.5 min. The potential chemical markers were identified for classification of the U. species samples by principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA). The results demonstrate the similarity and differences in alkaloids among the five U. species, which is helpful for the standardization and quality control of the medical materials of the U. Ramulus Cum Unics (URCU). Furthermore, with multivariate statistical analysis, the determined markers are more definite and useful for chemotaxonomy of the U. genus. PMID:25366313

  16. Alkaloid Accumulation in Catharanthus roseus Increases with Addition of Seawater Salts to the Nutrient Solution

    Institute of Scientific and Technical Information of China (English)

    WANG Jing-Yan; LIU Zhao-Pu

    2010-01-01

    A sand culture experiment was conducted to determine the effects of different seawater (5% and 10%) treatments on plant growth,inorganic ions,indole alkaloid concentrations and yields of Catharanthus roseus,in an effort to increase the alkaloid yield by artificial cultivation.The total fresh and dry weights and tissue K+ concentrations decreased,but Na+ concentrations increased in the plant roots,stems and leaves of C.roseus under seawater stress as compared to the control.The concentrations and yields of vindoline,catharanthine,vinblastine and vincristine increased under seawater stress.The concentrations and yields of these alkaloids were higher in 5% seawater-treated plants than those in the 10% seawater-treated plants.Considering the industrial production,5% seawater treatments could reduce the cost of producing alkaloid.In the control plants,the highest alkaloid concentrations reached a peak at 100 days after planting,suggesting that plant harvest must be optimized in terms of growth duration.

  17. Analysis of Indole Alkaloids from Rhazya stricta Hairy Roots by Ultra-Performance Liquid Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Amir Akhgari

    2015-12-01

    Full Text Available Rhazya stricta Decne. (Apocynaceae contains a large number of terpenoid indole alkaloids (TIAs. This study focused on the composition of alkaloids obtained from transformed hairy root cultures of R. stricta employing ultra-performance liquid chromatography-mass spectrometry (UPLC-MS. In the UPLC-MS analyses, a total of 20 TIAs were identified from crude extracts. Eburenine and vincanine were the main alkaloids followed by polar glucoalkaloids, strictosidine lactam and strictosidine. Secodine-type alkaloids, tetrahydrosecodinol, tetrahydro- and dihydrosecodine were detected too. The occurrence of tetrahydrosecodinol was confirmed for the first time for R. stricta. Furthermore, two isomers of yohimbine, serpentine and vallesiachotamine were identified. The study shows that a characteristic pattern of biosynthetically related TIAs can be monitored in Rhazya hairy root crude extract by this chromatographic method.

  18. Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

    OpenAIRE

    Chen, Qi-Yin; Liu, Yanxia; Cai, Weijing; Luesch, Hendrik

    2014-01-01

    Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound 1a and newly designed analogues a...

  19. Asymmetric Total Synthesis of (+)- and (−)-Clusianone and (+)- and (−)Clusianone Methyl Enol Ether via ACC Alkylation and Evaluation of their Anti-HIV Activity

    Science.gov (United States)

    Garnsey, Michelle R.; Matous, James A.; Kwiek, Jesse J.; Coltart, Don M.

    2011-01-01

    The total asymmetric synthesis of (+)- and (−)-clusianone and (+)- and (−)-clusianone methyl enol ether is reported. Asymmetric induction is achieved through the use of ACC alkylation, providing the key intermediates with an er of 99:1. The four synthetic compounds were evaluated for their anti-HIV activity. Both (+)- and (−)-clusianone displayed significant anti-HIV activity. PMID:21414776

  20. 粗叶悬钩子总生物碱对大鼠脂肪肝影响的脂肪染色图像分析%Image analysis on fat staining of fatty liver of rats with total alkaloids of Rubus Alceaefolius Poir

    Institute of Scientific and Technical Information of China (English)

    林如辉; 陈文列; 洪振丰; 黄关雅; 黄云梅; 徐柯

    2011-01-01

    Objective: To explore the effect on the fatty liver rats with the total alkaloids of Rubus Alceaefolius Poir (RAP) Methods: The 60 rats induced by CCl4 and treated by high fat diet. Then the rats divided six groups randomly: normal group,fatty liver model group, control by RAP low dose group, RAP medium dose group, RAP high dose group, Yishanfu group. The frozen sections were fat stained by Sudan Ⅳ, then observed the pathologic change in the treated groups, and quantitative analysis of the frozen section by positive areas, gray level, average optical density, integral optical density. Results: The treated groups by polysaccharides of RAP root and Yishanfu reduced and the pathologic change in the fatty liver rats , and the RAP high dose group reduced the gray level, average optical density and the integral optical density best, the difference was significant (P < 0. 05 ) . Conclusion: The RAP in high dose group can reduce the adipopexis in the fatty liver rats, and improve the pathological changes of fatty liver.%目的:探讨粗叶悬钩子(RAP)总生物碱对大鼠脂肪肝模型的影响.方法:以四氯化碳(CCl4)及高脂饮食造脂肪肝大鼠模型.将60只SD大鼠随机分为6组,即正常组,脂肪肝模型组,RAP总生物碱低剂量组、中剂量组、高剂量组,易善复对照组.观察各组大鼠经各种条件干预后肝脏冰冻切片的脂质变化,分别进行测量并定量分析脂肪染色阳性面积、灰度、平均光密度、积分光密度等.结果:RAP总生物碱各剂量组及易善复组均比模型组大鼠肝脏脂滴聚集变化轻,主要的测量指标平均灰度、平均光密度、积分光密度在高剂量组与模型组比较,差异具有显著性意义(P<0.05).结论:高剂量RAP总生物碱能减轻大鼠脂肪肝模型的脂滴聚集,改善脂肪肝的病变.

  1. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

    Science.gov (United States)

    Li, Yanran; Smolke, Christina D.

    2016-01-01

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4′-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID:27378283

  2. Two New C19-Diterpenoid Alkaloids from Delphinium davidii Franch.

    Institute of Scientific and Technical Information of China (English)

    Xiao Xia LIANG; Dong Lin CHEN; Feng Peng WANG

    2006-01-01

    Two new C19-diterpenoid alkaloids, davidisines A (1) and B (2) along with thirteen known alkaloids were isolated from the whole herb of Delphinium davidii Franch. Their structures were established by spectral methods, especially 2D NMR techniques.

  3. Biosynthesis of Monoterpenoid Indole Alkaloid Ajmaline Catalyzed by Novel Reductases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction One of the major root alkaloids of the Indian medicinal plant Rauvolfia serpenlina Benth. Ex Kurz is named ajmaline. The enzymatic biosynthesisof this alkaloid has been studied for a long time by our group[1].

  4. Actions of Piperidine Alkaloid Teratogens at Fetal Nicotinic Acetylcholine Receptors.

    Science.gov (United States)

    Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and clef...

  5. Benzylisoquinoline alkaloid biosynthesis in opium poppy.

    Science.gov (United States)

    Beaudoin, Guillaume A W; Facchini, Peter J

    2014-07-01

    Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy. PMID:24671624

  6. Monoterpenoid Indole Alkaloids from Catharanthus roseus Cultivated in Yunnan.

    Science.gov (United States)

    Wang, Bei; Liu, Lu; Chen, Ying-ying; Li, Qiong; Li, Dan; Liu, Va-ping; Luo, Xiao-dong

    2015-12-01

    A new monoterpenoid indole alkaloid, 15,20-dehydro-3α-(2-oxopropyl) coronaridine (1), along with sixteen analogues (2-17) were isolated from the leaves of Catharanthus roseus cultivated in Yunnan. The new alkaloid was elucidated on the basis of extensive spectroscopic analysis, and the known alkaloids were identified by comparison with the reported spectroscopic data. Among them, alkaloid 16 was isolated from Catharanthus for the first time. PMID:26882670

  7. Advances in total synthesis: A new approach to the synthesis of pteridic acids A and B [Avanços em síntese total: Uma nova abordagem para a síntese dos ácidos pterídicos A e B

    Directory of Open Access Journals (Sweden)

    David Rodrigues da Rocha

    2009-08-01

    Full Text Available This communication overview the total synthesis of pteridic acids A and B recently published by L. C. Dias and A. G. Salles Jr.in The Journal of Organic Chemistry which was achieved by a new synthetic route. These natural products are among the mostcomplex molecules already synthesized in Brazil.

  8. Total Synthesis of Cyclomarin A, a Marine Cycloheptapeptide with Anti-Tuberculosis and Anti-Malaria Activity.

    Science.gov (United States)

    Barbie, Philipp; Kazmaier, Uli

    2016-01-15

    An efficient synthetic protocol for the stereoselective synthesis of cyclomarin A is reported. Key steps in the syntheses of the building blocks are an asymmetric chelate-enolate Claisen rearrangement, an asymmetric hydrogenation, and highly diastereoselective additions of organozinc and -titanium reagents. PMID:26699807

  9. Stereoselective 6-exo radical cyclization using cis-vinyl sulfoxide: practical total synthesis of CTX3C.

    Science.gov (United States)

    Yamashita, Shuji; Ishihara, Yuuki; Morita, Hiroyuki; Uchiyama, Junichi; Takeuchi, Katsutoshi; Inoue, Masayuki; Hirama, Masahiro

    2011-03-25

    Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers. We report a highly stereoselective 6-exo radical cyclization/ring-closing olefin metathesis sequence to construct the syn/trans-fused polyether system. The new method was applied to the practical synthesis of ciguatoxin CTX3C. PMID:21250701

  10. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

    Science.gov (United States)

    Hufford, C D; Sharma, A S; Oguntimein, B O

    1980-10-01

    Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina. PMID:7420287

  11. Analysis of toxic alkaloids in body samples.

    Science.gov (United States)

    Beyer, Jochen; Drummer, Olaf H; Maurer, Hans H

    2009-03-10

    Many plants contain toxic alkaloids which may be dangerous to humans. Despite the large number of poisonous plants, cases of fatal plant poisonings are relatively rare. The frequencies of poisonings and the plants involved are often regionally specific. Plant poisonings can be aggregated into three categories: unintended ingestions, intended ingestions, and poisoning due to abuse of plant material. Unintended ingestions often occur in children or from a mix-up of plants and mushrooms in adults. Intended ingestions are common in homicides and suicides. Increasingly common is the abuse of plants for hallucinogenic reasons. Toxicological analysis of such alkaloids may help in diagnosis of poisoning or abuse cases. This review describes the toxic alkaloids aconitine, atropine, coniine, colchicine, cytisine, dimethyltryptamine, harmine, harmaline, ibogaine, kawain, mescaline, scopolamine, and taxine, which are often involved in fatal and non-fatal poisonings. The paper summarizes the symptoms of the intoxications and reviews the methods of detection of their toxic constituents in biological fluids. PMID:19147309

  12. Two New Alkaloids from Narcissus serotinus L.

    Directory of Open Access Journals (Sweden)

    Francesc Viladomat

    2010-10-01

    Full Text Available The Amaryllidaceae family is well known for the presence of an exclusive group of alkaloids with a wide range of biological activities. Narcissus serotinus L. is a plant belonging to this family and its geographical distribution is mainly located along the Mediterranean coast. In the present work, specimens collected near Casablanca (Morocco were used to study the alkaloid content of this species. Starting with 350 g of the whole plant we used standard extraction and purification procedures to obtain fractions and compounds for GC-MS and NMR analysis. As well as five known alkaloids, we isolated two new compounds: 1-O-(3´-acetoxybutanoyllycorine and narseronine. The latter has been previously published, but with an erroneous structure.

  13. Decontamination of alkaloid drugs with ionizing radiation

    International Nuclear Information System (INIS)

    The investigation of the effect of ionizing radiation (doses of 5, 10 and 25 kGy) on selected kinds of alkaloid drugs revealed a statistically significant decrease in the number of microorganisms (bacteria, moulds) in dependence on the dose. The largest decrease in the alkaloid content due to ionizing radiation took place in Radix veratri. in other drugs the differences are statistically insignificant. The alkaloid content never decreased to below the limit required by the pharmacopoeia. Infusions prepared from the parent material complied with the requirements of PhBs 4 for microbiological purity except for Folium belladonnae; in infusions from the irradiated drugs the decrease in the number of microorganisms correlated with the decrease found after the irradiation of the drug. (author). 7 tabs., 14 refs

  14. Aporphine alkaloids from Ocotea macrophylla (Lauraceae

    Directory of Open Access Journals (Sweden)

    Ludy Cristina Pabon

    2010-01-01

    Full Text Available Four aporphine alkaloids from the wood of Ocotea macrophylla (Lauraceae were isolated and characterized as (S-3-methoxy-nordomesticine (1, (S-N-ethoxycarbonyl-3-methoxy-nordomesticine (2, (S-N-formyl-3-methoxy-nordomesticine (3 and (S-N-methoxycarbonyl-3-methoxy-nordomesticine (4; alkaloids 2-4 are being report for the first time. The structure the isolated compounds were determined based on their spectral data and by comparison of their spectral data with values described in literature. The alkaloid fraction and compound 1 showed antifungal activity against Fusarium oxysporum f. sp. lycopersici and also compound 1 showed antimicrobial activity towards Staphylococcus aureus, Enterococcus faecalis as well.

  15. Aporphine alkaloids from Ocotea macrophylla (Lauraceae)

    Energy Technology Data Exchange (ETDEWEB)

    Pabon, Ludy Cristina; Cuca, Luis Enrique, E-mail: lcpabonb@unal.edu.c [Universidad Nacional de Bogota (Colombia). Facultad de Ciencias. Dept. de Quimica

    2010-07-01

    Four aporphine alkaloids from the wood of Ocotea macrophylla (Lauraceae) were isolated and characterized as (S)-3-methoxy-nordomesticine (1), (S)-N-ethoxycarbonyl-3-methoxy-nordomesticine (2), (S)-N-formyl-3-methoxy-nordomesticine (3) and (S)-N-methoxycarbonyl-3-methoxy-nordomesticine (4); alkaloids 2-4 are being report for the first time. The structure the isolated compounds were determined based on their spectral data and by comparison of their spectral data with values described in literature. The alkaloid fraction and compound 1 showed antifungal activity against Fusarium oxysporum f. sp. lycopersici and also compound 1 showed antimicrobial activity towards Staphylococcus aureus, Enterococcus faecalis as well. (author)

  16. Relationships among Ergot Alkaloids, Cytochrome P450 Activity, and Beef Steer Growth

    Directory of Open Access Journals (Sweden)

    Charles F. Rosenkrans

    2015-03-01

    Full Text Available Determining a grazing animal’s susceptibility to ergot alkaloids has been a research topic for decades. Our objective was to determine if the Promega™ P450-Glo assay could be used to indirectly detect ergot alkaloids or their metabolites in urine of steers. The first experiment validated the effects of ergot alkaloids [0, 20, and 40 μM of ergotamine (ET, dihydroergotamine (DHET, and ergonovine (EN] on human CYP3A4 using the P450-Glo assay (Promega™ V9800. With this assay, luminescence is directly proportional to CYP450 activity. Relative inhibition of in vitro cytochrome P450 activity was affected (P < 0.001 by an interaction between alkaloids and concentration. That interaction resulted in no concentration effect of EN, but within ET and DHET 20 and 40 µM concentrations inhibited CYP450 activity when compared with controls. In experiment 2, urine was collected from Angus-sired crossbred steers (n = 39; 216 ± 2.6 d of age; 203 ± 1.7 kg after grazing tall fescue pastures for 105 d. Non-diluted urine was added to the Promega™ P450-Glo assay, and observed inhibition (3.7 % ± 2.7 of control. Urine content of total ergot alkaloids (331.1 ng/mg of creatinine ± 325.7 was determined using enzyme linked immunosorbent assay. Urine inhibition of CYP450 activity and total alkaloids were correlated (r = -0.31; P < 0.05. Steers were genotyped at CYP450 single nucleotide polymorphism, C994G. Steer genotype affected (P < 0.03 inhibition of CYP450 activity by urine; heterozygous steers had the least amount of CYP450 inhibition suggesting that genotyping cattle may be a method of identifying animals that are susceptible to ergot alkaloids. Although, additional research is needed, we demonstrate that the Promega™ P450-Glo assay is sensitive to ergot alkaloids and urine from steers grazing tall fescue. With some refinement the P450-Glo assay has potential as a tool for screening cattle for their exposure to fescue toxins.

  17. Antimicrobial hasubanalactam alkaloid from Stephania glabra.

    Science.gov (United States)

    Semwal, Deepak Kumar; Rawat, Usha

    2009-03-01

    A novel hasubanalactam alkaloid, named glabradine, has been isolated from the tubers of Stephania glabra, together with three known quaternary protoberberine alkaloids, palmatine, dehydrocorydalmine and stepharanine. The structure of glabradine was assigned as 7-O-demethyl-N,O-dimethyloxostephinine, by means of rigorous spectroscopic analysis including 2 D NMR measurements. It was evaluated for antimicrobial activity against Staphylococcus aureus, S. mutans, Microsporum gypseum, M. canis and Trichophyton rubrum and displayed potent antimicrobial activity superior to those of novobiocin and erythromycin used as positive controls. PMID:19148860

  18. Antiprotozoal alkaloids from Psychotria prunifolia (Kunth) Steyerm

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Lucilia; Oliveira, Cecilia M.A. de; Faria, Emiret O.; Ribeiro, Laryssa C.; Carvalho, Brenda G., E-mail: lucilia@quimica.ufg.br [Instituto de Quimica, Universidade Federal de Goias, Campus II, Samambaia, Goiania, GO (Brazil); Silva, Cleuza C. da; Santin, Silvana M.O. [Departamento de Quimica, Universidade Estadual de Maringa, Maringa, PR (Brazil); Schuque, Ivania T.A.; Nakamura, Celso V.; Britta, Elisandra A.; Miranda, Nathielle [Departamento de Farmacia e Farmacologia, Universidade Estadual de Maringa, PR (Brazil); Iglesias, Amadeu H. [Waters Technologies do Brasil LTDA, Barueri, SP (Brazil); Delprete, Piero G. [VHerbier de Guyane, Institut de Recherche pour le Developpement (IRD), UMR AMAP, French Guiana (France)

    2012-07-01

    The continuity of the phyto chemical study of crude extracts of P. prunifolia's roots and branches led to the isolation of five indole-{beta}-carboline alkaloids. Among them, the 10-hydroxy-iso-deppeaninol and N-oxide-10-hydroxy-antirhine derivatives are described here for the first time. The structures were achieved through 1D and 2D NMR, IR and HRMS analyses. The branches and roots crude extracts and the alkaloids 14-oxoprunifoleine and strictosamide showed selective activity against L. amazonensis, with IC{sub 50} values of 16.0 and 40.7 {mu}g per mL, respectively. (author)

  19. Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera and Their Melanogenesis Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Toshio Morikawa

    2016-07-01

    Full Text Available A quantitative analytical method for five aporphine alkaloids, nuciferine (1, nornuciferine (2, N-methylasimilobine (3, asimilobine (4, and pronuciferine (5, and five benzylisoquinoline alkaloids, armepavine (6, norarmepavine (7, N-methylcoclaurine (8, coclaurine (9, and norjuziphine (10, identified as the constituents responsible for the melanogenesis inhibitory activity of the extracts of lotus flowers (the flower buds of Nelumbo nucifera, has been developed using liquid chromatography-mass spectrometry. The optimum conditions for separation and detection of these 10 alkaloids were achieved on a πNAP column, a reversed-phase column with naphthylethyl group-bonded silica packing material, with CH3CN–0.2% aqueous acetic acid as the mobile phase and using mass spectrometry equipped with a positive-mode electrospray ionization source. According to the protocol established, distributions of these 10 alkaloids in the petal, receptacle, and stamen parts, which were separated from the whole flower, were examined. As expected, excellent correlations were observed between the total alkaloid content and melanogenesis inhibitory activity. Among the active alkaloids, nornuciferine (2 was found to give a carbamate salt (2′′ via formation of an unstable carbamic acid (2′ by absorption of carbon dioxide from the air.

  20. Mutagenesis as a Functional Genomics Platform for Pharmaceutical Alkaloid Biosynthetic Gene Discovery in Opium Poppy

    International Nuclear Information System (INIS)

    Opium poppy (Papaver somniferum) accumulates the analgesic benzyl-isoquinoline alkaloids morphine, codeine and thebaine, and remains one of the world's most important medicinal plants. The development of varieties that accumulate valuable compounds, such as thebaine and codeine, but not morphine precludes the illicit synthesis of heroin (O,O-diacetylmorphine) and has led to the establishment of alternative cash crops. Novel cDNAs encoding a growing number of biosynthetic enzymes have been isolated, and various -omics resources including EST databases and DNA microarray chips have been established. However, the full potential of functional genomics as a tool for gene discovery in opium poppy remains limited by the relative inefficiency of genetic transformation protocols, which also restricts the application of metabolic engineering for both experimental and commercial purposes. We are establishing an effective functional genomics initiative based on induced mutagenesis and recently developed reverse genetics methodology, such as TILLING (Targeting Induced Local Lesions IN Genomes), with the aim of identifying biosynthetic genes that can be used to engineer opium poppy for the production of copious levels of high-value pharmaceutical alkaloids. Mutagenesis involves the treatment of seeds with ethyl methane sulfonate (EMS) or by fast-neutron bombardment (FNB). In preliminary experiments with EMS-treated seeds, the screening of 1,250 independent M2 plants led to the isolation of four mutants that displayed two distinctly altered alkaloid profiles. Two lines accumulated the central pathway intermediate reticuline and relatively low levels of morphine, codeine and thebaine compared to wild-type plants. Two other lines showed the unusual accumulation in the latex of the antimicrobial alkaloid sanguinarine, which is the product of a branch pathway distinct from that leading to morphine. The present status of -omics resources and functional genomics platforms available to

  1. Mutagenesis as a functional genomics platform for pharmaceutical alkaloid biosynthetic gene discovery in opium poppy

    International Nuclear Information System (INIS)

    Opium poppy (Papaver somniferum) accumulates the analgesic alkaloids morphine, codeine and thebaine, and remains one of the world's most important medicinal plants. The development of varieties that accumulate valuable compounds, such as thebaine and codeine, but not morphine precludes the illicit synthesis of heroin (O,O-diacetylmorphine) and has created opportunities to establish alternative cash crops. Novel cDNAs encoding more than a dozen biosynthetic enzymes have been isolated, and substantial EST databases and DNA microarray chips have been established. The full potential of functional genomics as a tool for gene discovery in opium poppy remains limited by the relative inefficiency of genetic transformation protocols, which also restricts the application of metabolic engineering for both experimental and commercial purposes. We are establishing an effective functional genomics initiative based on induced mutagenesis and TILLING (Targeting Induced Local Lesions IN Genomes) and with the aim of identifying biosynthetic genes that can be used to engineer opium poppy to produce copious levels of high-value pharmaceutical alkaloids. Mutagenesis involves the treatment of seeds by fast-neutron bombardment (FNB) or with ethyl methane sulfonate (EMS). Mutagenized opium poppy plants are cultivated in a secure underground growth facility in partnership with a Canadian biotechnology company. In preliminary experiments with EMS-treated seeds, the screening of 1,250 independent M2 plants led to the isolation of four mutants that displayed two distinctly altered alkaloid profiles. Two lines accumulated the central pathway intermediate (S)- reticuline and only low levels of morphine, codeine and thebaine. Two other lines showed the unusual accumulation of the antimicrobial alkaloid sanguinarine, which is the product of a branch pathway distinct from that leading to morphine, in the latex. The present status of -omics resources and functional genomics platforms available to

  2. Pharmacokinetics of Hoasca alkaloids in healthy humans.

    Science.gov (United States)

    Callaway, J C; McKenna, D J; Grob, C S; Brito, G S; Raymon, L P; Poland, R E; Andrade, E N; Andrade, E O; Mash, D C

    1999-06-01

    N,N-Dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine (THH) are the characteristic alkaloids found in Amazonian sacraments known as hoasca, ayahuasca, and yajè. Such beverages are characterized by the presence of these three harmala alkaloids, where harmine and harmaline reversibly inhibit monoamine oxidase A (MAO-A) while tetrahydroharmine weakly inhibits the uptake of serotonin. Together, both actions increase central and peripheral serotonergic activity while facilitating the psychoactivity of DMT. Though the use of such 'teas' has be known to western science for over 100 years, little is known of their pharmacokinetics. In this study, hoasca was prepared and administered in a ceremonial context. All four alkaloids were measured in the tea and in the plasma of 15 volunteers, subsequent to the ingestion of 2 ml hoasca/kg body weight, using gas (GC) and high pressure liquid chromatographic (HPLC) methods. Pharmacokinetic parameters were calculated and peak times of psychoactivity coincided with high alkaloid concentrations, particularly DMT which had an average Tmax of 107.5 +/- 32.5 min. While DMT parameters correlated with those of harmine, THH showed a pharmacokinetic profile relatively independent of harmine's. PMID:10404423

  3. Acetylcholinesterase-inhibiting Alkaloids from Zephyranthes concolor

    Directory of Open Access Journals (Sweden)

    Sebastien Arseneau

    2011-11-01

    Full Text Available The bulbs and aerial parts of Zephyranthes concolor (Lindl. Benth. & Hook. f. (Amaryllidaceae, an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution 1H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution 1H- and 13C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10−5 M, respectively, indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10−3 M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic.

  4. Saponins and alkaloids from Abuta grandifolia

    OpenAIRE

    Sayagh, C.; Long, C; Moretti, Christian; Lavaud, C.

    2012-01-01

    Five new bidesmosidic saponins (1-5), along with six known triterpenoid saponins, were isolated from the methanolic extracts of the leaves and twigs of Abuta grandifolia. The ethyl acetate extracts allowed the isolation of three tropoloisoquinolines and of one isoquinoline; all were known alkaloids. The structures of all compounds were elucidated on the basis of extensive spectroscopic data analysis.

  5. A new indole alkaloid from Ervatamia yunnanensis.

    Science.gov (United States)

    Jin, Yong-Sheng; Du, Jing-Ling; Chen, Hai-Sheng; Jin, Li; Liang, Shuang

    2010-01-01

    The stems of Ervatamia yunnanensis have afforded a new indole alkaloid, ervataine (1), whose structure was determined by spectroscopic analysis. Five known compounds, ibogaine (2) coronaridine (3), heyneanine (4), voacangine hydroxyindolenine (5) and coronaridine hydroxyindolenine (6), were also isolated. PMID:19647051

  6. Histrionicotoxin alkaloids finally detected in an ant

    DEFF Research Database (Denmark)

    Jones, Tappey H.; Adams, Rachelle Martha Marie; Spande, Thomas F.; Garraffo, H. Martin; Kaneko, Tetsuo; Schultz, Ted R.

    2012-01-01

    Workers of the ant Carebarella bicolor collected in Panama were found to have two major poison-frog alkaloids, cis- and trans-fused decahydroquinolines (DHQs) of the 269AB type, four minor 269AB isomers, two minor 269B isomers, and three isomers of DHQ 271D. For the first time in an ant, however......, the DHQs were accompanied by six histrionicotoxins (HTXs), viz., 283A, 285A, 285B, 285C, 287A, and 287D. This co-occurrence of the HTX and DHQ alkaloids is the usual pattern seen in dendrobatid frogs. This finding contrasts with our earlier study, where workers of a Brazilian ant, Solenopsis...... (Diplorhoptrum) sp., were found to have a very similar DHQ complex but failed to show HTXs. Several new DHQ alkaloids of MW 271 (named in the frog as 271G) are reported from the above ants that have both m/z 202 and 204 as major fragment ions, unlike the spectrum seen for the poison-frog alkaloid 271D, which has...

  7. Semisynthetic dimers of antiparkinsonic ergot alkaloids

    Czech Academy of Sciences Publication Activity Database

    Křen, Vladimír; Weignerová, Lenka; Kuzma, Marek; Jegorov, A.; Sedmera, Petr

    2001-01-01

    Roč. 55, č. 6 (2001), s. 1045-1056. ISSN 0385-5414 R&D Projects: GA AV ČR IAA4020901 Institutional research plan: CEZ:AV0Z5020903 Keywords : ergot alkaloids * antiparkinsonic activity Subject RIV: EE - Microbiology, Virology Impact factor: 0.970, year: 2001

  8. A New Alkaloid from Sinomenium acutum

    Institute of Scientific and Technical Information of China (English)

    Wei Ming CHENG; Feng QIU; Li Jun WU; Xin Sheng YAO

    2005-01-01

    Sinomenium acutum is widely used in East and South Asia for the treatment of many diseases, especially rheumatoid arthritis (RA). The chemical research on Sinomenium acutum led to the isolation of a new alkaloid compound (1). On the basis of chemical evidences and spectral analysis, 1 was identified as N-(1, 7-dimethoxylphenanthren-2-yl)acetamide.

  9. Proliferation inhibition and apoptosis induction effects of total alkaloid of Sophora Alopecuroides on mouse mammary tumor 4T1 cells in vitro%苦豆子总生物碱对小鼠乳腺癌4T1细胞体外增殖抑制及诱导凋亡作用的研究

    Institute of Scientific and Technical Information of China (English)

    李建光; 牛清芝; 杨晓艺; 曾诚; 黄伟

    2015-01-01

    Objective To explore the proliferation inhibition and apoptosis effect of the total alkaloid of so-phora alopecuroides (TASA)on mouse mammary tumor 4T1 in vitro.Methods TASA was extracted and purified,and then TASA was administrated to mouse mammary tumor 4T1 cells.The inhibitory effect of TASA at different concentrations on 4T1 cells was determinated by CCK-8 assay at the time point of 24 h. The effect of TASA on 4T1 cells apoptosis was detected by flow cytometry.Results With the drug con-centration of 5.00 mg/mL,4T1 cells survival rate was 63.05%,while the drug concentration reached to 10.00 mg/mL,4T1 cells survival rate was 20.30%,which suggested that 4T1 cells survival rate signifi-cantly declined with the increase of drug concentration.With the drug concentration of 6 .2 5 mg/mL,the apoptosis rate was 11.4%,while the drug concentration was 10.00 mg/mL,the apoptosis rate was 41.7%, which showed that apoptosis rate was increased significantly with the drug level increasing.Conclusion TASA could induce cell apoptosis of 4T1 cells,and it had a remarkable inhibitory effect on the prolifera-tion of 4T1 cells.%目的:研究苦豆子总生物碱对小鼠乳腺癌4T1细胞体外增殖抑制及诱导凋亡作用。方法苦豆子总生物碱提取并纯化,处理成澄清的药物溶液后用于细胞给药。CCK-8法测定不同浓度的苦豆子总生物碱作用24 h后4T1细胞存活率。流式细胞术检测给药24 h后4T1细胞凋亡率。结果与对照组比较,实验组药物浓度为5.00 mg/mL时,4T1细胞存活率为63.05%;药物浓度为10.00 mg/mL时,4T1细胞存活率为20.30%,随着给药浓度的增加,细胞存活率呈明显下降趋势。实验组药物浓度为6.25 mg/mL时,细胞凋亡率为11.4%;药物浓度为10.00 mg/mL时,细胞凋亡率为41.7%,随着给药浓度的增加,细胞凋亡率明显增加。结论苦豆子总生物碱能诱导细胞凋亡,对小鼠乳腺癌4T1细胞的增殖有明显抑制作用。

  10. Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

    Science.gov (United States)

    Steele, Andrew D; Keohane, Colleen E; Knouse, Kyle W; Rossiter, Sean E; Williams, Sierra J; Wuest, William M

    2016-05-11

    Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere. PMID:27096543

  11. Radical Beckmann Rearrangement and Its Application in the Formal Total Synthesis of Antimalarial Natural Product Isocryptolepine via C-H Activation.

    Science.gov (United States)

    Mahajan, Pankaj S; Humne, Vivek T; Tanpure, Subhash D; Mhaske, Santosh B

    2016-07-15

    The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and (18)O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples. The developed protocol and Pd-catalyzed intramolecular double C-H activation were used as key steps in the formal total synthesis of antimalarial natural product isocryptolepine. PMID:27377995

  12. Catharanthus roseus (L. G. Don - plant regeneration and alkaloids content

    Directory of Open Access Journals (Sweden)

    Mirosława Furmanowa

    2014-02-01

    Full Text Available We describe here a regeneration of plantlets of Catharanthus roseus (L. G. Don from shoot tips and axillary buds. Shoot tips were excised from 7-day-old seedlings and were incubated in solid Nitsch and Nitsch (NN medium supplemented with kinetin, benzyladenine (BA, indole-3-butyric acid (IBA and β-indolylacetic acid (IAA in various combinations. After two months in culture, regenerated rooted plantlets were cut and transferred to a new medium; the explants contained shoot tips or axillary buds. Four passages were done. We obtained about 200 rooting plantlets from one seedling. Then the plantlets were transferred to the soil and they grew under a foil tent. After five months of vegetation they were collected, dried and weighed. Chemical investigations of leaves of these plants were done. The vindoline and catharanthine were dominant alkaloids in the juvenile stage of plants (before blooming. Total amount of alkaloids, equal 2.95%, was gravimetrically determined in leaves of plants, after 4th passage, regenerated in vitro on NN medium supplemented with kinetin and IBA.

  13. Total Chemical Synthesis of a Heterodimeric Interchain Bis-Lactam-Linked Peptide: Application to an Analogue of Human Insulin-Like Peptide 3

    Science.gov (United States)

    Karas, John; Shabanpoor, Fazel; Hossain, Mohammed Akhter; Wade, John D.; Scanlon, Denis B.

    2013-01-01

    Nonreducible cystine isosteres represent important peptide design elements in that they can maintain a near-native tertiary conformation of the peptide while simultaneously extending the in vitro and in vivo half-life of the biomolecule. Examples of these cystine mimics include dicarba, diselenide, thioether, triazole, and lactam bridges. Each has unique physicochemical properties that impact upon the resulting peptide conformation. Each also requires specific conditions for its formation via chemical peptide synthesis protocols. While the preparation of peptides containing two lactam bonds within a peptide is technically possible and reported by others, to date there has been no report of the chemical synthesis of a heterodimeric peptide linked by two lactam bonds. To examine the feasibility of such an assembly, judicious use of a complementary combination of amine and acid protecting groups together with nonfragment-based, total stepwise solid phase peptide synthesis led to the successful preparation of an analogue of the model peptide, insulin-like peptide 3 (INSL3), in which both of the interchain disulfide bonds were replaced with a lactam bond. An analogue containing a single disulfide-substituted interchain lactam bond was also prepared. Both INSL3 analogues retained significant cognate RXFP2 receptor binding affinity. PMID:24288548

  14. Total Chemical Synthesis of a Heterodimeric Interchain Bis-Lactam-Linked Peptide: Application to an Analogue of Human Insulin-Like Peptide 3

    Directory of Open Access Journals (Sweden)

    John Karas

    2013-01-01

    Full Text Available Nonreducible cystine isosteres represent important peptide design elements in that they can maintain a near-native tertiary conformation of the peptide while simultaneously extending the in vitro and in vivo half-life of the biomolecule. Examples of these cystine mimics include dicarba, diselenide, thioether, triazole, and lactam bridges. Each has unique physicochemical properties that impact upon the resulting peptide conformation. Each also requires specific conditions for its formation via chemical peptide synthesis protocols. While the preparation of peptides containing two lactam bonds within a peptide is technically possible and reported by others, to date there has been no report of the chemical synthesis of a heterodimeric peptide linked by two lactam bonds. To examine the feasibility of such an assembly, judicious use of a complementary combination of amine and acid protecting groups together with nonfragment-based, total stepwise solid phase peptide synthesis led to the successful preparation of an analogue of the model peptide, insulin-like peptide 3 (INSL3, in which both of the interchain disulfide bonds were replaced with a lactam bond. An analogue containing a single disulfide-substituted interchain lactam bond was also prepared. Both INSL3 analogues retained significant cognate RXFP2 receptor binding affinity.

  15. Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways.

    Science.gov (United States)

    He, Kai; Hu, Yinran; Ma, Hang; Zou, Zongyao; Xiao, Yubo; Yang, Yong; Feng, Min; Li, Xuegang; Ye, Xiaoli

    2016-09-01

    It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert their hypolipidemic effects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140mg/kg for 35days) in high-fat and high-cholesterol induced hyperlipidemic B6 mice. After treatment, serum lipid parameters were determined, the expression of lipid metabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemic effects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2, LDLR, UCP2 and CYP7A1, inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge on hypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators of lipid homeostasis by modulation gut microbiota and hepatic lipid metabolism. PMID:27287254

  16. Influence of Precursor Availability on Alkaloid Accumulation by Transgenic Cell Line of Catharanthus roseus1

    Science.gov (United States)

    Whitmer, Serap; Canel, Camilo; Hallard, Didier; Gonçalves, Cecilia; Verpoorte, Robert

    1998-01-01

    We have used a transgenic cell line of Catharanthus roseus (L.) G. Don to study the relative importance of the supply of biosynthetic precursors for the synthesis of terpenoid indole alkaloids. Line S10 carries a recombinant, constitutively overexpressed version of the endogenous strictosidine synthase (Str) gene. Various concentrations and combinations of the substrate tryptamine and of loganin, the immediate precursor of secologanin, were added to suspension cultures of S10. Our results indicate that high rates of tryptamine synthesis can take place under conditions of low tryptophan decarboxylase activity, and that high rates of strictosidine synthesis are possible in the presence of a small tryptamine pool. It appears that the utilization of tryptamine for alkaloid biosynthesis enhances metabolic flux through the indole pathway. However, a deficiency in the supply of either the iridoid or the indole precursor can limit flux through the step catalyzed by strictosidine synthase. Precursor utilization for the synthesis of strictosidine depends on the availability of the cosubstrate; the relative abundance of these precursors is a cell-line-specific trait that reflects the metabolic status of the cultures. PMID:9490777

  17. An efficient and target-oriented sample enrichment method for preparative separation of minor alkaloids by pH-zone-refining counter-current chromatography.

    Science.gov (United States)

    Feng, Rui-Hong; Hou, Jin-Jun; Zhang, Yi-Bei; Pan, Hui-Qin; Yang, Wenzhi; Qi, Peng; Yao, Shuai; Cai, Lu-Ying; Yang, Min; Jiang, Bao-Hong; Liu, Xuan; Wu, Wan-Ying; Guo, De-An

    2015-08-28

    An efficient and target-oriented sample enrichment method was established to increase the content of the minor alkaloids in crude extract by using the corresponding two-phase solvent system applied in pH-zone-refining counter-current chromatography. The enrichment and separation of seven minor indole alkaloids from Uncaria rhynchophylla (Miq.) Miq. ex Havil(UR) were selected as an example to show the advantage of this method. An optimized two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3:7:1:9, v/v) was used in this study, where triethylamine (TEA) as the retainer and hydrochloric acid (HCl) as the eluter were added at the equimolar of 10mM. Crude alkaloids of UR dissolved in the corresponding upper phase (containing 10mM TEA) were extracted twice with lower phase (containing 10mM TEA) and lower phase (containing 10mM HCl), respectively, the second lower phase extract was subjected to pH-zone-refining CCC separation after alkalization and desalination. Finally, from 10g of crude alkaloids, 4g of refined alkaloids was obtained and the total content of seven target indole alkaloids was increased from 4.64% to 15.78%. Seven indole alkaloids, including 54mg isocorynoxeine, 21mg corynoxeine, 46mg isorhynchophylline, 35mg rhynchophylline, 65mg hirsutine, 51mg hirsuteine and 27mg geissoschizine methylether were all simultaneously separated from 2.5g of refined alkaloids, with the purity of 86.4%, 97.5%, 90.3%, 92.1%, 98.5%, 92.3%, and 92.8%, respectively. The total content and purities of the seven minor indole alkaloids were tested by HPLC and their chemical structures were elucidated by ESI-HRMS and (1)H NMR. PMID:26209189

  18. Determination of ephedrine alkaloids in botanicals and dietary supplements by HPLC-UV: collaborative study.

    Science.gov (United States)

    Roman, Mark C

    2004-01-01

    An international collaborative study was conducted of a high-performance liquid chromatography (HPLC)-UV method for the determination of the major (ephedrine [EP] and pseudoephedrine [PS]) and minor (norephedrine [NE], norpseudoephedrine [NP], methylephedrine [ME], and methylpseudoephedrine [MP]) alkaloids in selected dietary supplements representative of the commercially available products. Ten collaborating laboratories determined the ephedrine-type alkaloid content in 8 blind replicate samples. Five products contained ephedra ground herb or ephedra extract. These 5 products included ground botanical raw material of Ephedra sinica, a common powdered extract of Ephedra sinica, a finished product containing only Ephedra sinica ground botanical raw material, a complex multicomponent dietary supplement containing Ma Huang, and a high-protein chocolate flavored drink mix containing Ma Huang extract. In addition, collaborating laboratories received a negative control and negative control spiked with ephedrine alkaloids at high and low levels for recovery studies. Test extracts were treated to solid-phase extraction using a strong-cation exchange column to help remove interferences. The HPLC analyses were performed on a polar-embedded phenyl column using UV detection at 210 nm. Repeatability relative standard deviations (RSDr) ranged from 0.64-3.0% for EP and 2.0-6.6% for PS, excluding the high protein drink mix. Reproducibility relative standard deviations (RSDR) ranged from 2.1-6.6% for EP and 9.0-11.4% for PS, excluding the high protein drink mix. Recoveries ranged from 84.7-87.2% for EP and 84.6-98.2% for PS. The data developed for the minor alkaloids are more variable with generally unsatisfactory HORRATS (i.e., >2). However, since these alkaloids generally add little to the total alkaloid content of the products, the method gives satisfactory results in measuring total alkaloid content (RSDr 0.85-3.13%; RSDR 2.03-10.97%, HORRAT 0.69-3.23, exclusive of the results

  19. Accumulation of Monoterpenoid Indole Alkaloids in Periwinkle Seedlings ("Catharanthus roseus") as a Model for the Study of Plant-Environment Interactions

    Science.gov (United States)

    Miranda-Ham, Maria de Lourdes; Islas-Flores, Ignacio; Vazquez-Flota, Felipe

    2007-01-01

    Alkaloids are part of the chemical arsenal designed to protect plants against an adverse environment. Therefore, their synthesis and accumulation are frequently induced in response to certain environmental conditions and are mediated by chemical signals, which are formed as the first responses to the external stimulus. A set of experiments using…

  20. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  1. Total synthesis of pinnatoxins A and G and revision of the mode of action of pinnatoxin A.

    Science.gov (United States)

    Araoz, Romulo; Servent, Denis; Molgó, Jordi; Iorga, Bogdan I; Fruchart-Gaillard, Carole; Benoit, Evelyne; Gu, Zhenhua; Stivala, Craig; Zakarian, Armen

    2011-07-13

    Pinnatoxins belong to an emerging class of potent marine toxins of the cyclic imine group. Detailed studies of their biological effects have been impeded by unavailability of the complex natural product from natural sources. This work describes the development of a robust, scalable synthetic sequence relying on a convergent strategy that delivered a sufficient amount of the toxin for detailed biological studies and its commercialization for use by other research groups and regulatory agencies. A central transformation in the synthesis is the highly diastereoselective Ireland-Claisen rearrangement of a complex α,α-disubstituted allylic ester based on a unique mode for stereoselective enolization through a chirality match between the substrate and the lithium amide base. With synthetic pinnatoxin A, a detailed study has been performed that provides conclusive evidence for its mode of action as a potent inhibitor of nicotinic acetylcholine receptors selective for the human neuronal α7 subtype. The comprehensive electrophysiological, biochemical, and computational studies support the view that the spiroimine subunit of pinnatoxins is critical for blocking nicotinic acetylcholine receptor subtypes, as evidenced by analyzing the effect of a synthetic analogue of pinnatoxin A containing an open form of the imine ring. Our studies have paved the way for the production of certified standards to be used for mass-spectrometric determination of these toxins in marine matrices and for the development of tests to detect these toxins in contaminated shellfish. PMID:21644584

  2. Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities.

    Science.gov (United States)

    Medellin, Derek C; Zhou, Qiong; Scott, Robert; Hill, R Matthew; Frail, Sarah K; Dasari, Ramesh; Ontiveros, Steven J; Pelly, Stephen C; van Otterlo, Willem A L; Betancourt, Tania; Shuster, Charles B; Hamel, Ernest; Bai, Ruoli; LaBarbera, Daniel V; Rogelj, Snezna; Frolova, Liliya V; Kornienko, Alexander

    2016-01-14

    Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents. PMID:26641132

  3. Discovery of a P450-catalyzed step in vindoline biosynthesis: a link between the aspidosperma and eburnamine alkaloids.

    Science.gov (United States)

    Kellner, Franziska; Geu-Flores, Fernando; Sherden, Nathaniel H; Brown, Stephanie; Foureau, Emilien; Courdavault, Vincent; O'Connor, Sarah E

    2015-05-01

    Here we report the discovery of a cytochrome P450 that is required for the biosynthesis of vindoline, a plant-derived natural product used for semi-synthesis of several anti-cancer drugs. This enzyme catalyzes the formation of an epoxide that can undergo rearrangement to yield the vincamine-eburnamine backbone, thereby providing evidence for the long-standing hypothesis that the aspidosperma- and eburnamine-type alkaloids are biosynthetically related. PMID:25850027

  4. Antimicrobial alkaloids from Zanthoxylum tetraspermum and caudatum.

    Science.gov (United States)

    Nissanka, A P; Karunaratne, V; Bandara, B M; Kumar, V; Nakanishi, T; Nishi, M; Inada, A; Tillekeratne, L M; Wijesundara, D S; Gunatilaka, A A

    2001-04-01

    Two benzophenanthrene alkaloids, 8-acetonyldihydronitidine and 8-acetonyldihydroavicine were isolated from Zanthoxylum tetraspermum stem bark along with liriodenine, sesamin, lichexanthone and (+)-piperitol-gamma,gamma-dimethylallylether. The species endemic to Sri Lanka, Z. caudatum, contained sesamin, savinin, liriodenine, decarine and 8-O-desmethyl-N-nornitidine. 8-Acetonyldihydronitidine and 8-acetonyldihydroavicine showed significant antibacterial activity while the former along with liriodenine was strongly antifungal. Savinin exhibited potent spermicidal activity. Both savinin and sesamin exhibited significant insecticidal activity. PMID:11324918

  5. Pyrrolizidine alkaloids and diterpenes from Villasenoria orcuttii

    Energy Technology Data Exchange (ETDEWEB)

    Arciniegas, Amira; Perez-Castorena, Ana L.; Gonzalez, Karina; Vivar, Alfonso Romo de, E-mail: alperezc@unam.mx [Instituto de Quimica, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, DF (Mexico); Reyes-Lezama, Marisol [Centro Conjunto de Investigacion en Quimica Sustentable, Universidad Autonoma del Estado de Mexico-Universidad Nacional Autonoma de Mexico (UAEM-UNAM), Carretera Toluca-Atlacomulco, Estado de Mexico (Mexico); Villasenor, Jose Luis [Instituto de Biologia, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, DF, (Mexico)

    2013-07-15

    The chemical study of Villasenoria orcuttii, the only species of the genus Villasenoria, afforded three acyclic diterpenes, two of them described for the first time. Two pyrrolizidine alkaloids, florosenine and floridanine, among other known compounds were also isolated. The absolute configuration of floridanine was determined by X-ray analysis using anomalous dispersion with Cu K{sub {alpha}} radiation, and its {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) data were corrected. (author)

  6. Radioactive labelling of alkaloids with morphine skeleton

    International Nuclear Information System (INIS)

    Results achieved by the sup(14)C, sup(125)I and sup(3)H labelling of alkaloids with morphine skeleton for kinetic, receptor, metabolims and pharmacological investigations are summarized and evaluated. The methods for the preparation of sup(3)H labelled dihydromorphine, dihydroethylmorphine, dihydrocodeine, naloxone and naloxazone are described. The compounds have higher specific molar activity than those referred to in literature which makes them suitable for a number of investigations. (author)

  7. A new alkaloid from Solanum cathayanum

    Institute of Scientific and Technical Information of China (English)

    Fan Cheng; Xiang Li; Jun Zhi Wang

    2008-01-01

    A new alkaloid compound I was obtained from Solanum cathayanum, a folk medicine of Hubei Province, together with a knownalkaloid, orotic acid ethyl ester. On the basis of spectroscopic data and chemical methods, I was identified as 8-hydroxy-3-methoxy-5H-pyrido[2,1-c]pyrazin-5-one. Compound 1 can inhibit the production of NO in peritoneal macrophage of mice induced with LPS.The content of NO was determined by enzyme methods.

  8. Potential antimalarial activity of indole alkaloids

    OpenAIRE

    Frederich, Michel; Tits, Monique; Angenot, Luc

    2008-01-01

    New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This ...

  9. Initial Studies on Alkaloids from Lombok Medicinal Plants

    Directory of Open Access Journals (Sweden)

    John B. Bremner

    2001-01-01

    Full Text Available Initial investigation of medicinal plants from Lombok has resulted in the collection of 100 plant species predicted to have antimicrobial, including antimalarial, properties according to local medicinal uses. These plants represent 49 families and 80 genera; 23% of the plants tested positively for alkaloids. Among the plants testing positive, five have been selected for further investigation involving structure elucidation and antimicrobial testing on the extracted alkaloids. Initial work on structural elucidation of some of the alkaloids is reported briefly.

  10. A new monoterpenoid oxindole alkaloid from Hamelia patens micropropagated plantlets.

    Science.gov (United States)

    Paniagua-Vega, David; Cerda-García-Rojas, Carlos M; Ponce-Noyola, Teresa; Ramos-Valdivia, Ana C

    2012-11-01

    Chemical studies on Hamelia patens (Rubiaceae) micropropagated plantlets allowed production of a new monoterpenoid oxindole alkaloid, named (-)-hameline (7), together with eight known alkaloids, tetrahydroalstonine (1), aricine (2), pteropodine (3), isopteropodine (4), uncarine F (5), speciophylline (6), palmirine (8), and rumberine (9). The structure of the new alkaloid was assigned on the basis of 1D and 2D NMR spectroscopy, mass spectrometry, and molecular modeling. PMID:23285803

  11. Design, Synthesis, and Investigation of Protein Kinase C Inhibitors: Total Syntheses of (+)-Calphostin D, (+)- Phleichrome, Cercosporin and New Photoactive Perylenequinones

    OpenAIRE

    Morgan, Barbara J.; Dey, Sangeeta; Johnson, Steven W.; Kozlowski, Marisa C.

    2009-01-01

    The total syntheses of the PKC inhibitors (+)-calphostin D, (+)-phleichrome, cercosporin, and 10 novel perylenequinones are detailed. The highly convergent and flexible strategy developed employed an enantioselective oxidative biaryl coupling and a double cuprate epoxide opening, allowing the selective syntheses of all the possible stereoisomers in pure form. In addition, this strategy permitted rapid access to a broad range of analogs, including those not accessible from the natural products...

  12. Evaluation of antibiotic potential of alkaloids of Tribulus terrestris L. against some pathogenic microorganisms

    Directory of Open Access Journals (Sweden)

    Alka Jindal

    2013-01-01

    Full Text Available Context: Antibiotic resistance has become a global concern. There has been an increasing incidence of multiple resistances in human pathogenic microorganisms in recent years, largely due to indiscriminate use of commercial antimicrobial drugs commonly employed in the treatment of infectious diseases. Tribulus terrestris (Family: Zygophyllaceae is a well-known medicinal plant and has been used world-wide for the treatment of infectious diseases. Alkaloids are group of naturally occurring chemical compounds, which are known to have antimicrobial properties. Aim: The present study is designed to evaluate the antimicrobial potential of alkaloids of T. terrestris L. Materials and Methods: Alkaloids extracted from different parts (root, stem, leaf and fruits of T. terrestris were screened by Disc diffusion assay against three bacterial strains: gram positive (Staphylococcus aureus, gram negative (Escherichia coli and Proteus mirabilis and two fungal strains: Aspergillus flavus and Aspergillus niger. Minimum inhibitory concentration of the extracts was evaluated by micro broth dilution method while minimum bactericidal/fungicidal concentration was determined by sub culturing the relevant samples. Total activity of the extracts against each sensitive test pathogens was also calculated. Statistical Analysis: Mean value and standard error mean were calculated for the results of disc diffusion assay and data were analysed by one-way analysis of variance and P values were considered significant at P < 0.05. Results: The alkaloid extracts of T. terrestris showed significant antibacterial potential as all test extracts were found active against both the gram positive and negative bacteria, but were inactive against the tested fungi. Conclusion: The present study indicates the broad spectrum antibacterial potential of the alkaloids of T. terrestris, hence may be exploited for future antibacterial drugs.

  13. Total synthesis of avermectins part 2: enantioselective synthesis of the C10-C25 northern fragment and final steps for the construction of the 22,23-dihydroavermectin B1b aglycone

    International Nuclear Information System (INIS)

    The total synthesis of the aglycone of 22,23-dihydroavermectin B1b involves a retrosynthetic two building-blocks approach. A Stille Pd(O) catalysed cross-coupling reaction is carried out between a northern C10-C25 E-vinylstannane and a southern C1-C9 vinyl iodide. The final steps include successive removal of the carboxyl β-(trimethylsilyl)ethyl protecting group of the intermediate secoester, macrolactonization under Yonemitsu's conditions and removal of the 5-O-TBS protecting group. These last steps have been carried out with the aid of a relay study from commercial Ivermectin; a macrolactone opening reaction of the aglycone in the presence of Ti(OiPr)4 has been developed where the crucial Δ3,4 double bond as well as the configuration at C-2 where totally preserved. (authors). 46 refs., 10 figs., 2 tabs

  14. Binding Parameters of Alkaloids Berberine and Sanguinarine with DNA

    CERN Document Server

    Gumenyuk, V G; Kutovyy, S Yu; Yashchuk, V M; Zaika, L A

    2012-01-01

    We study the interaction of berberine and sanguinarine (plant alkaloids) with DNA in aqueous solutions, by using optical spectroscopy methods (absorption and fluorescence). The dependencies of alkaloid spectral characteristics on the concentration ratio N/c between the DNA base pairs and alkaloid molecules in the solutions are considered, and the manifestations of the alkaloid-DNA binding are revealed. The character of binding is found to depend on N/c. The parameters of the binding of berberine and sanguinarine with DNA are determined, by using the modified Scatchard and McGhee-von Hippel equations

  15. Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.

    Science.gov (United States)

    Gunasekera, Sarath P; Li, Yang; Ratnayake, Ranjala; Luo, Danmeng; Lo, Jeannette; Reibenspies, Joseph H; Xu, Zhengshuang; Clare-Salzler, Michael J; Ye, Tao; Paul, Valerie J; Luesch, Hendrik

    2016-06-01

    A new dimeric macrolide xylopyranoside, cocosolide (1), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR spectroscopy, HRMS, X-ray diffraction studies and Mosher's analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A-D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide (1) along with its [α,α]-anomer (26) and macrocyclic core (28), thus leading to the confirmation of the structure of natural 1. The convergent synthesis featured Wadsworth-Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, α-selective glycosidation and β-selective glycosidation. Compounds 1 and 26 potently inhibited IL-2 production in both T-cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide also suppressed the proliferation of anti-CD3-stimulated T-cells in a dose-dependent manner. PMID:27139508

  16. Evaluation of Antioxidant and Antibacterial Activities of Aqueous, Methanolic and Alkaloid Extracts from Mitragyna Speciosa (Rubiaceae Family) Leaves

    OpenAIRE

    Mohd I. Mohd. Said; Sreenivasan Sasidharan; Surash Ramanathan; Sabariah Ismail; Juzaili Bin Azizi; Suhanya Parthasarathy; Sharif Mahsufi Mansor

    2009-01-01

    Studies on the antioxidant and antimicrobial activities of Mitragyna speciosa leaf extracts are lacking. In this study the antioxidant properties of water, methanolic and alkaloid M. speciosa leaf extracts were evaluated using the DPPH (2,2-diphenyl-1- picrylhydrazyl) radical scavenging method. The amount of total phenolics and flavanoid contents were also estimated. The DPPH IC50 values of the aqueous, alkaloid and methanolic extracts were 213.4, 104.81 and 37.08 μg/mL, respectively. The tot...

  17. Autoradiographic studies on mucilage synthesis in Chara vulgaris antheridium with the use of 3H-fucose in total darkness and light

    International Nuclear Information System (INIS)

    Autoradiographic studies with 3H-fucose have shown that this precursor of polysaccharide compounds is incorporated into manubria and antheridial mucilage of Chara vulgaris both in the light and in the darkness. The dynamic of this process is lower in total darkness. The decrease in overall labelling of antheridium (manubria an mucilage) reflects secondary metabolic changes both in proliferative phase and in spermiogenesis. The pulse (2 and 5 min) incubations with the isotope confirm the intensive mucilage translocation which at later developmental stages is more dynamic than at earlier ones. It can explain previously observed decrease in manubria radioactivity at later stages after long (40 min) incubation, because PAS-positive polysaccharide synthesis is simultaneous with their fast translocation to the antheridial space. The present and previous autoradiographic and cytophotometric data taken altogether confirm the assumption about a nutritive role of mucilage filling Chara antheridium during the process of spermatogenesis. (author). 19 refs, 7 figs

  18. Autoradiographic studies on mucilage synthesis in Chara vulgaris antheridium with the use of {sup 3}H-fucose in total darkness and light

    Energy Technology Data Exchange (ETDEWEB)

    Gosek, A. [Lodz Univ. (Poland)

    1996-12-31

    Autoradiographic studies with {sup 3}H-fucose have shown that this precursor of polysaccharide compounds is incorporated into manubria and antheridial mucilage of Chara vulgaris both in the light and in the darkness. The dynamic of this process is lower in total darkness. The decrease in overall labelling of antheridium (manubria an mucilage) reflects secondary metabolic changes both in proliferative phase and in spermiogenesis. The pulse (2 and 5 min) incubations with the isotope confirm the intensive mucilage translocation which at later developmental stages is more dynamic than at earlier ones. It can explain previously observed decrease in manubria radioactivity at later stages after long (40 min) incubation, because PAS-positive polysaccharide synthesis is simultaneous with their fast translocation to the antheridial space. The present and previous autoradiographic and cytophotometric data taken altogether confirm the assumption about a nutritive role of mucilage filling Chara antheridium during the process of spermatogenesis. (author). 19 refs, 7 figs.

  19. Synthesis, structure and total conductivity of A-site doped LaTiO3−δ perovskites

    International Nuclear Information System (INIS)

    Highlights: • A-site divalent alkaline earth metal doped LaTiO3−δ perovskites were synthesised by sol–gel method. • Structural studies revealed no change in crystal symmetry but change in cell dimensions after doping. • After doping divalent cations in A-site, an enhancement in total conductivity was observed in LaTiO3−δ. • Temperature dependent electrical property was observed in all synthesised perovskites. - Abstract: Oxygen deficient perovskites LaTiO3−δ and La0.8A0.2TiO3−δ (A = Ba, Sr, Ca) were synthesized by sol–gel method. The effect of divalent dopants on microstructure is investigated in detail using X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The oxidation states of La3+ and Ti3+ ions have been deduced using X-ray Photoelectron Spectroscopy (XPS). Impedance spectroscopy was used to analyze the total conductivity, an increase in conductivity was observed after doping in the A-site with divalent cations Ba, Ca and Sr. Among the investigated perovskites La0.8Ca0.2TiO3−δ exhibited the maximum conductivity of 1.22 × 10−2 S/cm in air atmosphere at 650 °C

  20. Synthesis, structure and total conductivity of A-site doped LaTiO{sub 3−δ} perovskites

    Energy Technology Data Exchange (ETDEWEB)

    Bradha, M. [Nanotech Research Facility, PSG Institute of Advanced Studies, Coimbatore 641 004, TN (India); Hussain, S.; Chakravarty, Sujay [UGC-DAE CSR, Kalpakkam Node, Kokilamedu 603 104, TN (India); Amarendra, G. [UGC-DAE CSR, Kalpakkam Node, Kokilamedu 603 104, TN (India); Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102, TN (India); Ashok, Anuradha, E-mail: anu.machina@gmail.com [Nanotech Research Facility, PSG Institute of Advanced Studies, Coimbatore 641 004, TN (India)

    2015-03-25

    Highlights: • A-site divalent alkaline earth metal doped LaTiO{sub 3−δ} perovskites were synthesised by sol–gel method. • Structural studies revealed no change in crystal symmetry but change in cell dimensions after doping. • After doping divalent cations in A-site, an enhancement in total conductivity was observed in LaTiO{sub 3−δ}. • Temperature dependent electrical property was observed in all synthesised perovskites. - Abstract: Oxygen deficient perovskites LaTiO{sub 3−δ} and La{sub 0.8}A{sub 0.2}TiO{sub 3−δ} (A = Ba, Sr, Ca) were synthesized by sol–gel method. The effect of divalent dopants on microstructure is investigated in detail using X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The oxidation states of La{sup 3+} and Ti{sup 3+} ions have been deduced using X-ray Photoelectron Spectroscopy (XPS). Impedance spectroscopy was used to analyze the total conductivity, an increase in conductivity was observed after doping in the A-site with divalent cations Ba, Ca and Sr. Among the investigated perovskites La{sub 0.8}Ca{sub 0.2}TiO{sub 3−δ} exhibited the maximum conductivity of 1.22 × 10{sup −2} S/cm in air atmosphere at 650 °C.

  1. New monoterpenoid alkaloids from the aerial parts of Uncaria hirsuta.

    Science.gov (United States)

    Jia, Jun-Feng; Zhang, Yuan; Huang, Xiao-Jun; Zhang, Sheng-Yuan; Tian, Hai-Yan; Wang, Lei; Ye, Wen-Cai

    2014-01-01

    To investigate the chemical constituents of medicinal plant Uncaria hirsuta, three new monoterpenoid alkaloids, named hirsutanines A-C (1-3), were isolated. Their structures with absolute configurations were elucidated by means of NMR, X-ray diffraction and CD analysis. Compound 3 was the first dimeric monoterpenoid alkaloid obtained from genus Uncaria. PMID:24684175

  2. Effects of Ergot Alkaloids on Bovine Sperm Motility In Vitro

    Science.gov (United States)

    Ergot alkaloids are synthesized by endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum (Schreb.) S.J. Darbyshire). Our objective was to determine direct effects of ergot alkaloids (ergotamine, dihydroergotamine and ergonovine) on the motility of bovine spermatozoa in vit...

  3. Studies of interaction between two alkaloids and double helix DNA

    International Nuclear Information System (INIS)

    This article presents the study on the interaction of two alkaloids (matrine and evodiamine) and hs-DNA by absorption, fluorescence, circular dichroism (CD), DNA melting and viscosity experiments. The spectroscopic studies suggested that two alkaloids can bind to DNA through an intercalative mode. The viscosity measurement and thermal denaturation also indicated that two alkaloids can intercalate to DNA. The binding constants (KA) and the number of binding sites (n) were determined. At the same time, some significant thermodynamic parameters of the binding of the alkaloids to DNA were obtained. Competitive binding studies revealed that alkaloids had an effect on ethidium bromide (EB) bound DNA. In addition, it was also proved that the fluorescence quenching was influenced by ionic strength. - Highlights: • Interaction between two alkaloids and DNA is studied by spectral methods. • The binding constant and the binding sites between two alkaloids and DNA are obtained. • There are a classical intercalative mode between alkaloids and DNA. • The binding of matrine with DNA is weaker than that of evodiamine. • It is important for us to understand the alkaloids–DNA interactions at a molecular level

  4. Pyrrolizidine alkaloids from Bulgarian species of the genus Senecio

    Directory of Open Access Journals (Sweden)

    NADEZHDA KOSTOVA

    2006-12-01

    Full Text Available Nine Bulgarian species from the genus Senecio were studied phytochemically and/or by GC-MS analysis. Senecivernine-N-oxide was isolated and identified by spectral data for the first time. Different types of pyrrolizidine alkaloids were tested for cytotoxicity on murine lymphocytes. At a concentration of 100 µg/ml, the alkaloid retroisosenine showed immunosuppressive effect.

  5. In vitro antibacterial screening of Cryptolepis sanguinolenta alkaloids.

    Science.gov (United States)

    Paulo, A; Duarte, A; Gomes, E T

    1994-10-01

    The ethanol and aqueous crude extracts and five alkaloids isolated from the roots of Crytolepis sanguinolenta (Lindl.) Schlechter were screened for antibacterial activity against 7 reference strains by the twofold serial broth microdilution assay. The ethanol extract and the alkaloids cryptolepine and cryptoheptine inhibited the growth of all strains tested except that of Pseudomonas aeruginosa. PMID:7853864

  6. Antioxidant activities of alkaloid extracts of two Algerian species of Fumaria : Fumaria capreolata and Fumaria bastardii

    Directory of Open Access Journals (Sweden)

    Fadila Maiza-Benabdesselam

    2007-11-01

    Full Text Available The antioxidant activities of the alkaloid extracts of Fumaria capreolata (L. and Fumaria bastardii (L. were determined by measuring their reducing power, their ability to inhibit linoleic acid peroxidation, and 2,2-diphenyl-β-picrylhydrazyl (DPPH radical scavenging activities. Total quinolizidine alkaloid contents were found to be 426 mg/100 g (F.capreolata and 521 mg/100g (F.bastardii. Both plant extracts exhibited strong total antioxidant activity, however, extract of F.bastardii was more potent then F.capreolata. Concentrations of 100, 300, and 500µg mL -1 showed 42, 55, 65 and 48.3, 60, and 67.8 % inhibition of lipid peroxidation of linoleic acid emulsion, for F.capreolata and F.bastardii extracts, respectively. On the other hand, 500µg mL -1 of the standard antioxidant butylated hydroxyianisole (BHA, quercetine, and caffeine exhibited 80, 56.2, and 64.3% inhibition of lipid peroxidation, respectively. In addition, the both extracts had effective reducing power, DPPH free radical scavenging activity at 250 and 50 µg mL -1. The isoquinoline alkaloids, stylopine, protopine, fumaritine, fumaricine, fumarophycine, fumariline, fumarofine were determined by GC-MS from the aerial parts of F. capreolata and F. bastardii.

  7. Total synthesis of gracilioether F. Development and application of Lewis acid promoted ketene–alkene [2+2] cycloadditions and late-stage C—H oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Rasik, Christopher M. [Indiana Univ., Bloomington, IN (United States); Brown, M. Kevin [Indiana Univ., Bloomington, IN (United States)

    2014-12-22

    The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene–alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp³)—H oxidation. The synthesis requires only eight steps from norbornadiene.

  8. Revealing the Mechanisms behind SnO2 Nanoparticle Formation and Growth during Hydrothermal Synthesis: An In Situ Total Scattering Study

    Energy Technology Data Exchange (ETDEWEB)

    Billinge S. J.; Jensen, K.M.O.; Christensen, M.; Juhas, P.; Tyrsted, C.; Bojesen, E.D.; Lock, N.; Iversen, B.B.

    2012-03-15

    The formation and growth mechanisms in the hydrothermal synthesis of SnO{sub 2} nanoparticles from aqueous solutions of SnCl{sub 4} {center_dot} 5H{sub 2}O have been elucidated by means of in situ X-ray total scattering (PDF) measurements. The analysis of the data reveals that when the tin(IV) chloride precursor is dissolved, chloride ions and water coordinate octahedrally to tin(IV), forming aquachlorotin(IV) complexes of the form [SnCl{sub x}(H{sub 2}O){sub 6-x}]{sup (4-x)+} as well as hexaaquatin(IV) complexes [Sn(H{sub 2}O){sub 6-y}(OH){sub y}]{sup (4-y)+}. Upon heating, ellipsoidal SnO{sub 2} nanoparticles are formed uniquely from hexaaquatin(IV). The nanoparticle size and morphology (aspect ratio) are dependent on both the reaction temperature and the precursor concentration, and particles as small as 2 nm can be synthesized. Analysis of the growth curves shows that Ostwald ripening only takes place above 200 C, and in general the growth is limited by diffusion of precursor species to the growing particle. The c-parameter in the tetragonal lattice is observed to expand up to 0.5% for particle sizes down to 2-3 nm as compared to the bulk value. SnO{sub 2} nanoparticles below 3-4 nm do not form in the bulk rutile structure, but as an orthorhombic structural modification, which previously has only been reported at pressures above 5 GPa. Thus, adjustment of the synthesis temperature and precursor concentration not only allows control over nanoparticle size and morphology but also the structure.

  9. Effect of a 60-day oral gavage of a crude alkaloid extract from Chromolaena odorata leaves on hormonal and spermatogenic indices of male rats.

    Science.gov (United States)

    Yakubu, Musa T

    2012-01-01

    The present study was aimed at investigating the effects of the crude alkaloids isolated from Chromolaena odorata leaves on the hormonal and spermatogenic indices of male rats. The alkaloids obtained from C odorata leaves using standard methods were administered to male rats for 60 days at the doses of 250, 500, and 1000 mg/kg body weight. Thin-layer chromatographic analysis of the alkaloid mixture produced 8 spots, 3 of which were alkaloids with R(f) values of 0.41, 0.49, and 0.55 as confirmed by the formation of orange color and creamy precipitates with both Dragendorff and Mayer reagents, respectively. The alkaloids were represented in the extract by a yield of 20.28 g, corresponding to a percentage yield of 90.05% of the total extract of 22.52 g. The final body weights of both the control and alkaloid-treated animals increased significantly (P odorata leaves may be due to nonavailability or deprivation of testosterone to the target organ. This lack of testosterone may have consequential effects on the reproductive process of the male rat. PMID:22653963

  10. Influence of Nonpolar Substances on the Extraction Efficiency of Six Alkaloids in Zoagumhwan Investigated by Ultra Performance Liquid Chromatography and Photodiode Array Detection

    Directory of Open Access Journals (Sweden)

    Shijing Liu

    2012-11-01

    Full Text Available A reverse phase ultra performance liquid chromatography and photodiode array (UPLC-PDA detection method was established for the determination of six alkaloids in Zoagumhwan (ZGW, and further for investigating the influence of nonpolar substances on the extraction efficiency of these alkaloids. The method was based on a BEH C18 (50 mm × 2.1 mm, 1.7 μm column and mobile phase of aqueous phosphoric acid and acetonitrile including 0.05% buffer solution under gradient elution. ZGW samples of ZGW I, II, III and IV were obtained and prepared by pre-processing the crude materials of Coptidis rhizoma and Evodiae fructus using four technologies, namely direct water decoction, removal of nonpolar substances in Evodiae fructus by supercritical fluid extraction (SFE, removal of nonpolar substances in ZGW by SFE and removal of nonpolar substances in ZGW by steam distillation. The developed and validated UPLC-PDA method was precise, accurate and sensitive enough based on the facts that the six alkaloids showed good regression (r > 0.9998, the limit of detections and quantifications for six alkaloids were less than 28.8 and 94.5 ng/mL, respectively, and the recovery was in the range of 98.56%–103.24%. The sequence of the total contents of six alkaloids in these samples was ZGW II > ZGW IV > ZGW III > ZGW I. ZGW II, in which nonpolar substances, including essential oils, were firstly removed from Evodiae fructus by SFE, had the highest content of the total alkaloids, indicating that extraction efficiency of the total alkaloids could be remarkably increased after Evodiae fructus being extracted by SFE.

  11. Antifungal Indole Alkaloids from Winchia calophylla.

    Science.gov (United States)

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively. PMID:27002397

  12. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  13. Chirality and Numbering of Substituted Tropane Alkaloids

    Directory of Open Access Journals (Sweden)

    Philippe Christen

    2011-08-01

    Full Text Available The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of 1H-NMR anisochrony (Δd induced by the Mosher’s chiral auxiliary reagents (R-(-- and (S-(+-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl, to determine the absolute configuration of (3R,6R-3α-hydroxy-6b-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae. These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives.

  14. Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae).

    Science.gov (United States)

    Zanatta, Francielle; Gandolfi, Renan Becker; Lemos, Marivane; Ticona, Juan Carlos; Gimenez, Alberto; Clasen, Bruna Kurz; Cechinel Filho, Valdir; de Andrade, Sérgio Faloni

    2009-07-15

    As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following protocols in mice: nonsteroidal anti-inflammatory drug (NSAID)/bethanecol-induced ulcer, ethanol/HCl-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity were also evaluated, using the pylorus ligated model. Treatment using doses of 50, 125 and 250 mg/kg of G. longiflora alkaloid extract and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, total lesion area, and percentage of lesion, in comparison with the negative control groups in all the models evaluated. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in gastric pH. The main alkaloid of the plant, 2-phenylquinoline, was also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, it significantly inhibited ulcerative lesions. However, this effect was less than that of the alkaloid extract. All these results taken together show that G. longiflora displays gastroprotective activity, as evidenced by its significant inhibition of the formation of ulcers induced by different models. There are indications that mechanisms involved in anti-ulcer activity are related to a decrease in gastric secretion and an increase in gastric mucus content. Also, there is evidence of involvement of NO in the gastroprotector mechanisms. These effects may be attributed, at least in part, to the presence of some alkaloids, particularly 2-phenylquinoline. PMID:19497430

  15. Identification and simultaneous quantification of five alkaloids in Piper longum L. by HPLC-ESI-MS(n) and UFLC-ESI-MS/MS and their application to Piper nigrum L.

    Science.gov (United States)

    Liu, Hao-Long; Luo, Rong; Chen, Xiao-Qing; Ba, Yin-Ying; Zheng, Li; Guo, Wei-Wei; Wu, Xia

    2015-06-15

    A simple, effective and suitable UFLC-ESI-MS/MS method was firstly developed to simultaneously determine five characteristic constituents (piperine, piperlonguminine, Δα,β-dihydropiperlonguminine, pellitorine and piperanine) of Piper longum L. The total alkaloids of P. longum L. was prepared. The alkaloid contents of Piper nigrum L. and P. longum L. were compared. The analysis was carried out in multiple reaction monitoring scan mode. The method showed a good specificity, linearity (R(2)>0.995), stability (RSDnigrum, P. longum had lower piperine content but was enriched in the other four alkaloids. PMID:25660876

  16. Total synthesis of the bicyclo[6.3.0]undecane-based sesquiterpene (±)-asterisca-3(15),6-diene. Revision of the relative stereochemistry of the natural product

    OpenAIRE

    Mehta, Goverdhan; Umarye, Jayant D

    2001-01-01

    The first total synthesis of the novel bicyclic sesquiterpene hydrocarbon asterisca-3(15),6-diene is reported. As a consequence, the natural product is shown to possess structure 4 with a trans-5,8 ring fusion and not the previously assigned cis-asterisca-3(15),6-diene 3.

  17. Total synthesis and in vitro bioevaluation of clavaminols A, C, H & deacetyl clavaminol H as potential chemotherapeutic and antibiofilm agents.

    Science.gov (United States)

    Vijai Kumar Reddy, T; Jyotsna, A; Prabhavathi Devi, B L A; Prasad, R B N; Poornachandra, Y; Ganesh Kumar, C

    2016-09-14

    A highly concise and expedient total synthesis of bioactive clavaminols (1-4) has been executed using commercially available achiral compound decanol. The synthetic strategy relied on trans-Wittig olefination, Sharpless asymmetric epoxidation, regioselective azidolysis and in situ detosylation followed by reduction as key reactions with good overall yield. Based on biological evaluation studies of all the synthesized compounds, it was observed that the clavaminol A (1) exhibited good cytotoxicity against DU145 and SKOV3 cell lines with IC50 value of 10.8 and 12.5 μM, respectively. Clavaminol A (1) and deacetyl clavaminol H (3) displayed selective promising inhibition towards Gram-positive pathogenic bacterial strains and showed good antifungal activity against the tested Candida strains. In addition, compounds 1 and 3 have demonstrated significant bactericidal activity. Compound 3 was found to be equipotent to the standard drug Miconazole displaying MFC value of 15.6 μg/mL against Candida albicans MTCC 854, C. albicans MTCC 1637, C. albicans MTCC 3958 and Candida glabrata MTCC 3019. Compounds 1 and 3 were also able to inhibit the biofilm formation of Micrococcus luteus MTCC 2470 and Staphylococcus aureus MLS16 MTCC 2940. Clavaminol A (1) increased the levels of reactive oxygen species (ROS) accumulation in M. luteus MTCC 2470. PMID:27187861

  18. Total synthesis of (-)- and (+)-tedanalactam

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Parameswaran, P.S.; Tilve, S.G.

    , S. G. J. Org. Chem. 2009, 74, 3591. (b) Patre, R.; Gawas, S.; Sen, S.; Parameswaran, P. S.; Tilve, S. G. Tetrahedron Lett. 2007, 48, 3517. (c) Parvatkar, P.; Parameswaran, P. S.; Tilve, S. G. Tetrahedron Lett. 2007, 48, 7870. (d) Majik, M. S... for their therapeutic usage and a few are isolated as natural products. Tedanalactam, a cis-3,4-epoxy-2-piperidone 1 was first isolated from sponge Tedania ignis in 1994 by Cronan and Cardellina. 3 Recently in 2007, Lago and Kato 4 found it in leaves of Piper...

  19. [Total synthesis of nordihydroguaiaretic acid].

    Science.gov (United States)

    Wu, A X; Zhao, Y R; Chen, N; Pan, X F

    1997-04-01

    beta-Keto ester(5) was obtained from vanilin through etherification, oxidation and condensation with acetoacetic ester, (5) on oxidative coupling reaction by NaOEt/I2 produced dimer (6) in high yield. Acid catalyzed cyclodehydration of (6) gave the furan derivative(7), and by a series of selective hydrogenation nordihydroguaiaretic acid, furoguaiacin dimethyl ether and dihydroguaiaretic acid dimethyl ether were synthesized. PMID:11499030

  20. Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots.

    Science.gov (United States)

    Paulo, A; Gomes, E T; Steele, J; Warhurst, D C; Houghton, P J

    2000-02-01

    The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines. PMID:10705730

  1. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    XU MaoJun; DONG JuFang

    2007-01-01

    Bax, a mammalian pro-apoptotic member of the Bcl-2 family, triggers hypersensitive reactions when expressed in plants. To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells, we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter. The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied. Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0- and 5.5-fold of the control cells. Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str, two key genes in terpenoid indole alkaloid biosynthetic pathway of Catharanthus roseus cells, and stimulates the accumulation of defense-related protein PR1 in the cells, showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway. Thus, our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  2. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bax,a mammalian pro-apoptotic member of the Bcl-2 family,triggers hypersensitive reactions when expressed in plants.To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells,we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter.The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied.Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0-and 5.5-fold of the control cells.Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str,two key genes in terpenoid indole alkaloid bio-synthetic pathway of Catharanthus roseus cells,and stimulates the accumulation of defense-related protein PR1 in the cells,showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway.Thus,our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  3. Ergot Alkaloids in Feed for Pekin Ducks: Toxic Effects, Metabolism and Carry Over into Edible Tissues

    Directory of Open Access Journals (Sweden)

    Sven Dänicke

    2015-06-01

    Full Text Available Hardened sclerotia (ergots of Claviceps purpurea contaminate cereal grains and contain toxic ergot alkaloids (EA. Information on EA toxicity in ducks is scarce. Therefore, the aim of the growth experiment (Day 0–49, n = 54/group was to titrate the lowest observed adverse effect level (LOAEL for total ergot alkaloids (TEA. A control diet was prepared without ergots, and the diets designated Ergot 1 to 4 contained 1, 10, 15 and 20 g ergot per kg diet, respectively, corresponding to TEA contents of 0.0, 0.6, 7.0, 11.4 and 16.4 mg/kg. Sensitivity of ducks to EA was most pronounced at the beginning of the experiment when feed intake decreased significantly by 9%, 28%, 41% and 47% in groups Ergot 1 to 4, respectively, compared to the control group. The experiment was terminated after two weeks for ducks exposed to Ergot 3 and 4 due to significant growth retardation. Ergot alkaloid residues in edible tissues were lower than 5 ng/g. Bile was tested positive for ergonovine (=ergometrine = ergobasine with a mean concentration of 40 ng/g. Overall, the LOAEL amounted to 0.6 mg TA/kg diet suggesting that ducks are not protected by current European Union legislation (1 g ergot/kg unground cereal grains.

  4. Ergot alkaloids in feed for Pekin ducks: toxic effects, metabolism and carry over into edible tissues.

    Science.gov (United States)

    Dänicke, Sven

    2015-06-01

    Hardened sclerotia (ergots) of Claviceps purpurea contaminate cereal grains and contain toxic ergot alkaloids (EA). Information on EA toxicity in ducks is scarce. Therefore, the aim of the growth experiment (Day 0-49, n = 54/group) was to titrate the lowest observed adverse effect level (LOAEL) for total ergot alkaloids (TEA). A control diet was prepared without ergots, and the diets designated Ergot 1 to 4 contained 1, 10, 15 and 20 g ergot per kg diet, respectively, corresponding to TEA contents of 0.0, 0.6, 7.0, 11.4 and 16.4 mg/kg. Sensitivity of ducks to EA was most pronounced at the beginning of the experiment when feed intake decreased significantly by 9%, 28%, 41% and 47% in groups Ergot 1 to 4, respectively, compared to the control group. The experiment was terminated after two weeks for ducks exposed to Ergot 3 and 4 due to significant growth retardation. Ergot alkaloid residues in edible tissues were lower than 5 ng/g. Bile was tested positive for ergonovine (=ergometrine = ergobasine) with a mean concentration of 40 ng/g. Overall, the LOAEL amounted to 0.6 mg TA/kg diet suggesting that ducks are not protected by current European Union legislation (1 g ergot/kg unground cereal grains). PMID:26043275

  5. Analytical chemical study of alkaloid fraction of methanolic extract of Croton baillonianus (AUBL) leaves

    International Nuclear Information System (INIS)

    The objective of the present study has been to extract and isolate the alkaloids from leaves of Croton baillonianus, corresponding to the methanolic extract by exclusion chromatography with Sephadex LH-20 followed by a purification by high performance liquid chromatography, obtaining six alkaloids. Two low polarity alkaloid and two glycoside alkaloids were analyzed by Electronic System impact mass spectrometry; these alkaloids belong to bencylisoquinolinic type; the study has connection to the determination of its antioxidant, antiulcerose and cytotoxic properties. (author).

  6. The distribution of inole alkaloids in different organs of Catharanthus roseus G. Don. (Vinca rosea L)

    OpenAIRE

    Hassan Ebrahimzadeh; Azra Ataei -Azimi4 Mohammad-Reza Noori-Dafoi

    1996-01-01

    The study of alkaloid extract of the leaf of Vinca rosea by TLC showed the existence of 13 bands, 7 bands of them were: Serpentine, Vincristine, Vinblastine, Ajmaline, Catharantine, Vindoline and Ajmalicine. The existence of these 7 alkaloids was confirmed in the young leaves, old leaves and the roots of the plant by HPLC. Furthermore, two alkaloids with the short retention times and one alkaloid with the medium retention time in the young leaf, three alkaloids with the short retention time a...

  7. Qualitative determination of indole alkaloids of Tabernaemontana fuchsiaefolia (Apocynaceae)

    International Nuclear Information System (INIS)

    This paper describes a fast and efficient procedure to separate and identify indole alkaloids from the ethanolic extract of Tabernaemontana fuchsiaefolia (Apocynaceae). The alkaloidal fractions obtained from ethanolic extracts of leaves and stem barks and root barks were fractioned and analyzed by Thin-Layer Chromatography (TLC) and by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The following indole alkaloids were identified: ibogamine, coronaridine, ibogaine pseudoindoxyl, voacangine hydroxyindolenine, voacangine pseudoindoxyl, tabernanthine, catharanthine, voacangine, 19-oxovoacangine, 10-hydroxycoronaridine, affinisine, 16-epi-affinine, voachalotine, ibogaline, and conopharyngine. (author)

  8. Qualitative determination of indole alkaloids of Tabernaemontana fuchsiaefolia (Apocynaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Zocoler, Marcos A. [Universidade do Oeste Paulista, Presidente Prudente, SP (Brazil). Dept. de Farmacos e Medicamentos; Oliveira, Arildo J.B. de [Universidade Estadual de Maringa, PR (Brazil). Dept. de Farmacia e Farmacologia; Sarragiotto, Maria H.; Grzesiuk, Viviane L.; Vidotti, Gentil J. [Universidade Estadual de Maringa, PR (Brazil). Dept. de Quimica]. E-mail: gjvidotti@uem.br

    2005-11-15

    This p describes a fast and efficient procedure to separate and identify indole alkaloids from the ethanolic extract of Tabernaemontana fuchsiaefolia (Apocynaceae). The alkaloidal fractions obtained from ethanolic extracts of leaves and stem barks and root barks were fractioned and analyzed by Thin-Layer Chromatography (TLC) and by Gas Chromatography coupled to Mass Spectrometry (GC-MS). The following indole alkaloids were identified: ibogamine, coronaridine, ibogaine pseudoindoxyl, voacangine hydroxyindolenine, voacangine pseudoindoxyl, tabernanthine, catharanthine, voacangine, 19-oxovoacangine, 10-hydroxycoronaridine, affinisine, 16-epi-affinine, voachalotine, ibogaline, and conopharyngine. (author)

  9. Two New N-Oxide Alkaloids from Stemona cochinchinensis

    Directory of Open Access Journals (Sweden)

    Ligen Lin

    2014-12-01

    Full Text Available Two new N-oxide alkaloids with pyrrolo[1,2-α]azepine skeleton, namely isoneostemocochinine-N-oxide (1 and neostemocochinine-N-oxide (2, as well as three known alkaloids with pyrido[1,2-α]azepine skeletons, were isolated and identified from the roots of Stemona cochinchinensis (Stemonaceae. The structures of these compounds were elucidated by 1D- and 2D-NMR spectra and other spectroscopic studies. Additionally, the 1H- and 13C-NMR characteristic of N-oxide Stemona alkaloids was summarized. Stemokerrin showed potent anti-tussive activity on citric acid-induced guinea pig model.

  10. Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution.

    Science.gov (United States)

    Nge, Choy-Eng; Chong, Kam-Weng; Thomas, Noel F; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2016-05-27

    Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells. PMID:27077800

  11. Antifouling Alkaloids from Crinum augustum (Amaryllidaceae

    Directory of Open Access Journals (Sweden)

    John Refaat

    2009-01-01

    Full Text Available Fractionation and purification of the ethanolic extract of the bulbs of Crinum augustum Rox. (Amaryllidaceae cultivated in Egypt yielded five alkaloids 6-methoxy-crinamine (1 , crinamine (2 , buphanisine (3 , ungeremine (4 , and hippadine (5 ; two fatty acid derivatives: myristic acid ethyl ester (6 and palmitic acid ethyl ester (7 ; four terpenoidal and steroidal compounds: ursolic acid (8 , β-sitosterol-O- β glucopyranoside (9 and mixture of β--sitosterol (10 and stigmasterol (11 . The structures of all compounds were determined by interpretation of their spectroscopic data; 1D ( 1 H and 13 C, 2D (HSQC, COSY, DQF, NOE and HMBC NMR; MS and UV analyses. The compounds (1 -4 and (6-8 were tested towards biofouling activity using larvae of barnacle Balance amphitrie. Significant activities of 1, 2 and 3 with EC 50 1.8, 1.2 and 0.75 μg/mL respectively, were observed.

  12. Investigation of Aconitine-type Alkaloids from Processed Tuber of Aconitum carmiechaeli by HPLC-ESI-MS/MSn

    Institute of Scientific and Technical Information of China (English)

    YUE Hao; PI Zi-feng; ZHAO Yu-feng; SONG Feng-rui; LIU Zhi-qiang; LIU Shu-ying

    2007-01-01

    @@ Introduction Aconitine-type alkaloids isolated from the roots of Aconitum carmiechaeli show a potential toxicity and a broad spectrum of bioactivity[1-4]. On the basis of the C8-substituent of C19-diterpenoid skeleton, aconitinetype alkaloids can be divided into diester-diterpenoid alkaloids( DDAs), monoester-diterpenoid alkaloids(MDAs), and lipo-alkaloids( Fig. 1 ).

  13. Two bromotyrosine alkaloids from the sponge Psammaplysilla purpurea

    Digital Repository Service at National Institute of Oceanography (India)

    Tilvi, S.; Parameswaran, P.S.; Naik, C.G.

    The sponge Psammaplysilla purpurea (Order: Verongidae, Family: Aplysinellidae) is a well known source for several bromotyrosine alkaloids of unique structural features and exhibiting promising biological activities such as cytotoxicity...

  14. A New Binary Carbazole Alkaloid from Murraya koenigii

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new binary carbazole alkaloid, 8, 8"-biskoenigine (1), along with its monomer,kocnigine, was isolated from the dried leaves of Murraya koenigii collected in Xishuangbanna,Yunnan province. The structure of 1 was established by spectroscopic methods.

  15. Leishmanicidal Evaluation of Tetrahydroprotoberberine and Spirocyclic Erythrina-Alkaloids

    Directory of Open Access Journals (Sweden)

    Daniel R. Callejon

    2014-05-01

    Full Text Available Leishmaniasis is one of the World’s most problematic diseases in developing countries. Traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. In this work, two alkaloids 1 and 2 were obtained from Corydalis govaniana Wall and seven alkaloids 3–9, were obtained from Erythrina verna. The structures of the compounds were confirmed by mass spectrometry and 1D- and 2D-NMR spectroscopy. The leishmanicidal activity of compounds 1–9 against Leishmania amazonensis was tested on promastigote forms and cytotoxicity against J774 (macrophage cell line was assessed in vitro. Compound 1 showed potent activity (IC50 = 0.18 µg/mL, compared with the standard amphotericin B (IC50 = 0.20 µg/mL. The spirocyclic erythrina-alkaloids showed lower leishmanicidal activity than dibenzoquinolizine type alkaloids.

  16. A new phenanthridine alkaloid from Hymenocallis x festalis.

    Science.gov (United States)

    Hohmann, J; Forgo, P; Szabó, P

    2002-12-01

    Investigation of the alkaloid fraction of the bulbs of Hymenocallis x festalis yielded a new natural product, 3-methoxy-8,9-methylenedioxy-3,4-dihydrophenanthridine (1). The structure was elucidated on the basis of spectroscopic data. PMID:12490249

  17. Ergot alkaloids induce vasoconstriction of bovine foregut vasculature

    Science.gov (United States)

    Alkaloids produced by the Neotyphodium coenophialum endophyte in association with tall fescue (Lolium arundinaceum) are imputed to cause peripheral symptoms of fescue toxicosis. We hypothesized that theses compounds could correspondingly affect foregut vasculature. The objective of this study was to...

  18. New bromotyrosine alkaloids from the marine sponge Psammaplysilla purpurea

    Digital Repository Service at National Institute of Oceanography (India)

    Tilvi, S.; Rodrigues, C.; Naik, C.G.; Parameswaran, P.S.; Wahidullah, S.

    Seven new bromotyrosine alkaloids Purpurealidin A, B, C, D, F, G, H and the known compounds Purealidin Q, Purpurealidin E, 16-Debromoaplysamine-4 and Purpuramine I have been isolated from the marine sponge Psammaplysilla purpurea. Their structure...

  19. Quinolizidines alkaloids: Petrosin and xestospongins from the sponge Oceanapia sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, K.S.; Das, B.; Naik, C.G.

    having di-hetro atom rings, from the ethyl acetate extract of the sponge. The compounds exhibited moderate to high activities against some microorganisms and clinical isolates. The structures of the alkaloids were elucidated by NMR and ESIMS spectroscopic...

  20. Reviewing colchicaceae alkaloids – perspectives of evolution on medicinal chemistry

    DEFF Research Database (Denmark)

    Larsson, Sonny; Rønsted, Nina

    2014-01-01

    . In this review an approach of taking phylogenetic classification into account in evaluating colchicine and related phenethylisoquinoline alkaloids from the family Colchicaceae will be applied. Following on the trends of utilizing evolutionary reasoning in inferring mechanisms in eg. drug resistance...