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Sample records for alkaloids total synthesis

  1. Total Synthesis of Securinega Alkaloids

    Institute of Scientific and Technical Information of China (English)

    T. Honda

    2005-01-01

    @@ 1Introduction Naturally occurring Securinega alkaloids (1-4) (Fig. 1)[1], with their wide range of structural and stereochemical features, continue to provide challenging synthetic targets, since these alkaloids exhibit attractive biological activities. Securinine (1), isolated from Securinega suffruticosa [2], was structurally determined to contain an indolizidine skeleton with an azabicyclo[3.2.1 ]octane system together with an α, β-unsaturated γ-lactone ring. This alkaloid has been clinically used in Russia as a CNS stimulating drug[3], and has been shown to act as a stereospecific antagonist at the GABA binding site of the GABAA-receptor complex[4].Viroallosecurinine (2), a diastereoisomeric alkaloid of securinine, was also isolated from the leaves of Securinega virosa[5] as a cytotoxic alkaloid exhibiting a MIC of 0.48 μg/mL for Ps. aeruginosa and Staph.aureus[6]. This alkaloid is recognized to be bactericidal since the yields of MIC/MBC were less than 1[7].

  2. Total synthesis of the Daphniphyllum alkaloid daphenylline

    Science.gov (United States)

    Lu, Zhaoyong; Li, Yong; Deng, Jun; Li, Ang

    2013-08-01

    The Daphniphyllum alkaloids are a large class of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They display a remarkable range of biological activities, including anticancer, antioxidant, and vasorelaxation properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the predominately aliphatic Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on a sterically compact hexacyclic scaffold. Herein, we describe the first total synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction, inspired by Dixon's seminal work, were exploited to construct the bridged 6,6,5-tricyclic motif of the natural product at an early stage, and the aromatic moiety was forged through a photoinduced olefin isomerization/6π-electrocyclization cascade followed by an oxidative aromatization process.

  3. Total synthesis of the indolizidine alkaloid tashiromine

    Directory of Open Access Journals (Sweden)

    McElhinney Alison D

    2008-01-01

    Full Text Available Abstract Background Tashiromine 1 is a naturally occurring indolizidine alkaloid. It has been the subject of thirteen successful total syntheses to date. Our own approach centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric approaches, depending upon the choice of the allylsilane metathesis partner. Results The use of the allyltrimethylsilane cross-metathesis approach enables the rapid construction of the key cyclisation precursor 3 (3 steps from commercial materials, which undergoes acid-induced cyclisation to give the desired bicyclic indolizidine skeleton as a 96:4 mixture of diastereomers. Simple functional group interconversions allowed the completion of the total synthesis of racemic tashiromine in six steps (19% overall yield. Three chiral α-alkoxyallylsilanes (12,14 and 15 were prepared in enantioenriched form and their cross-metathesis reactions studied as part of a putative asymmetric approach to tashiromine. In the event, α-hydroxysilane 12 underwent isomerisation under the reaction conditions to acylsilane 17, while silanes 14 and 15 were unreactive towards metathesis. Conclusion A concise, stereoselective total synthesis of racemic tashiromine has been developed. Attempts to translate this into an asymmetric synthesis have thus far been unsuccessful.

  4. Total Synthesis of the Zoanthamine Alkaloid

    Institute of Scientific and Technical Information of China (English)

    M. Miyashita

    2005-01-01

    @@ 1Introduction The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have attracted much attention from a wide area of science, because of their distinctive biological and pharmacological properties as well as their chemical structures with stereochemical complexity.Namely, norzoanthamine (1)[1] can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug[1], whereas zoanthamine (2)[2] has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects[2]. See Fig. 1.

  5. Total synthesis of the bridged indole alkaloid apparicine.

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    Bennasar, M-Lluïsa; Zulaica, Ester; Solé, Daniel; Roca, Tomàs; García-Díaz, Davinia; Alonso, Sandra

    2009-11-06

    An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents.

  6. Total synthesis of the congested propellane alkaloid (-)-acutumine.

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    Castle, Steven L

    2014-08-01

    The enantioselective total synthesis of (-)-acutumine is described. The synthetic strategy was inspired by the premise that the cyclohexenone ring could be derived from an aromatic precursor. After successful construction of a propellane model system, an initial attempt to prepare the spirocyclic subunit was thwarted by incorrect regioselectivity in a radical cyclization. A second-generation approach involving a radical-polar crossover reaction was successful, and the chemistry developed in the aforementioned model system was then applied to synthesize the natural product. Key reactions included a phenolic oxidation, a diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, an acid-promoted cyclization of a secondary amine onto an α,β-unsaturated ketal, and a regioselective methyl enol etherification of a 1,3-diketone.

  7. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

    OpenAIRE

    2015-01-01

    An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenter...

  8. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline.

    Science.gov (United States)

    Sharpe, Robert J; Johnson, Jeffrey S

    2015-10-02

    An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products.

  9. [Total synthesis of biologically active alkaloids using bio-inspired indole oxidation].

    Science.gov (United States)

    Ishikawa, Hayato

    2015-01-01

    Many tryptophan-based dimeric diketopiperazine (DKP) alkaloids including WIN 64821 and ditryptophenaline, which exhibit fascinating biological activities, have been isolated from fungi. These alkaloids possess a unique architecture; therefore several total syntheses of these compounds have been accomplished via bio-inspired reactions. Despite these elegant strategies, we were convinced that a more direct bio-inspired solution for the preparation of tryptophan-based DKP alkaloids was possible because in a true biosynthesis, direct dimerization of tryptophan occurs in aqueous media without incorporation of a protecting group on the substrates. Thus we developed direct bio-inspired dimerization reactions in aqueous, acidic media, along with a novel biomimetic pathway, to provide C2-symmetric and non-symmetric dimeric compounds from commercially available amine-free tryptophan derivatives using Mn(OAc)3, VOF3, and V2O5 as one-electron oxidants. In addition, concise two-pot or three-step syntheses of the naturally occurring dimeric DKP alkaloids (+)-WIN 64821, (-)-ditryptophenaline, and (+)-naseseazine B were accomplished with total yields of 20%, 13%, and 20%, respectively. The present synthesis has several noteworthy features: 1) the tryptophan-based C2-symmetric and non-symmetric dimeric key intermediates can be prepared on a multigram scale in one step; 2) the developed oxidation reaction was carried out in aqueous, acidic solution without deactivation of the metal oxidants; 3) protection of the primary amine can be avoided by salt formation in aqueous acid; 4) for the total two-pot operation, the reaction media are environmentally friendly water and ethanol; 5) satisfactory total yields are obtained compared with previously reported syntheses.

  10. 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.

  11. 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.

  12. Strategies toward the Total Synthesis of Calyciphylline B-type Alkaloids: A Computational Perspective Aided by DFT Analysis.

    Science.gov (United States)

    Chattopadhyay, Amit Kumar; Berger, Gilles; Hanessian, Stephen

    2016-06-17

    Herein we describe synthetic efforts toward the total synthesis of calyciphylline B-type alkaloids. In the process, we disclose a detailed DFT study of equilibrium geometries and transition states that explains the stereochemical outcome during the formation of critical intermediates. X-ray crystallographic analysis reveals interesting conformational features in the naturally occurring deoxycalyciphylline B and its synthetic congeners.

  13. Stereospecific approach to the synthesis of ring-A oxygenated sarpagine indole alkaloids. Total synthesis of the dimeric indole alkaloid P-(+)-dispegatrine and six other monomeric indole alkaloids.

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    Edwankar, Chitra R; Edwankar, Rahul V; Namjoshi, Ojas A; Liao, Xuebin; Cook, James M

    2013-07-05

    The first regio- and stereocontrolled total synthesis of the bisphenolic, bisquaternary alkaloid (+)-dispegatrine (1) has been accomplished in an overall yield of 8.3% (12 reaction vessels) from 5-methoxy-d-tryptophan ethyl ester (17). A crucial late-stage thallium(III) mediated intermolecular oxidative dehydrodimerization was employed in the formation of the C9-C9' biaryl axis in 1. The complete stereocontrol observed in this key biaryl coupling step is due to the asymmetric induction by the natural sarpagine configuration of the monomer lochnerine (6) and was confirmed by both the Suzuki and the oxidative dehydrodimerization model studies on the tetrahydro β-carboline (35). The axial chirality of the lochnerine dimer (40) and in turn dispegatrine (1) was established by X-ray crystallography and was determined to be P(S). Additionally, the first total synthesis of the monomeric indole alkaloids (+)-spegatrine (2), (+)-10-methoxyvellosimine (5), (+)-lochnerine (6), lochvinerine (7), (+)-sarpagine (8), and (+)-lochneram (11) were also achieved via the common pentacyclic intermediate 16.

  14. Accessing the structural diversity of pyridone alkaloids: concise total synthesis of rac-citridone A.

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    Fotiadou, Anna D; Zografos, Alexandros L

    2011-09-01

    A unique route to the structural diversity of pyridone alkaloids is described based on the concept of a common synthetic strategy. Three different core structure analogues corresponding to akanthomycin, septoriamycin A, and citridone A have been prepared by using a highly selective and novel carbocyclization reaction.

  15. A global and local desymmetrization approach to the synthesis of steroidal alkaloids: stereocontrolled total synthesis of paspaline.

    Science.gov (United States)

    Sharpe, Robert J; Johnson, Jeffrey S

    2015-04-22

    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.

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

    OpenAIRE

    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.

  17. An efficient synthesis of loline alkaloids

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    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.

  18. Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins

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    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.

  19. A stereoselective approach to indolizidine and pyrrolizidine alkaloids: total synthesis of (-)-lentiginosine, (-)-epi-lentiginosine and (-)-dihydroxypyrrolizidine.

    Science.gov (United States)

    Kauloorkar, Shruti Vandana; Jha, Vishwajeet; Jogdand, Ganesh; Kumar, Pradeep

    2014-07-07

    A simple and highly efficient approach to hydroxylated pyrrolizidine and indolizidine is developed from an aldehyde as a starting material using organocatalytic and asymmetric dihydroxylation reactions as key steps. Its application to the total synthesis of (-)-lentiginosine, (-)-epi-1,2-lentiginosine and (-)-dihydroxypyrrolizidine is also reported.

  20. Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine.

    Science.gov (United States)

    Trost, Barry M; Osipov, Maksim

    2015-11-09

    The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed.

  1. A stereodivergent strategy for the preparation of corynantheine and ipecac alkaloids, their epimers, and analogues: efficient total synthesis of (-)-dihydrocorynantheol, (-)-corynantheol, (-)-protoemetinol, (-)-corynantheal, (-)-protoemetine, and related natural and nonnatural compounds.

    Science.gov (United States)

    Zhang, Wei; Bah, Juho; Wohlfarth, Andreas; Franzén, Johan

    2011-12-01

    Here we present a general and common catalytic asymmetric strategy for the total and formal synthesis of a broad number of optically active natural products from the corynantheine and ipecac alkaloid families, for example, indolo[2,3-a]- and benzo[a]quinolizidines. Construction of the core alkaloid skeletons with the correct absolute and relative stereochemistry relies on an enantioselective and diastereodivergent one-pot cascade sequence followed by an additional diastereodivergent reaction step. This allows for enantio- and diastereoselective synthesis of three out of four possible epimers of the quinolizidine alkaloids that begin from common and easily accessible starting materials by using a common synthetic route. Focus has been made on excluding protecting groups and limiting isolation and purification of synthetic intermediates. This methodology is applied in the total synthesis of the natural products (-)-dihydrocorynantheol, (-)-hirsutinol, (-)-corynantheol, (-)-protometinol, (-)-dihydrocorynantheal, (-)-corynantheal, (-)-protoemetine, (-)-(15S)-hydroxydihydrocorynantheol, and an array of their nonnatural epimers. The potential of this strategy is also demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives. We also report the formal synthesis of (+)-dihydrocorynantheine, (-)-emetine, (-)-cephaeline, (-)-tubulosine, and (-)-deoxytubulosine.

  2. Recent Advances in the Synthesis of Morphine and Related Alkaloids

    Science.gov (United States)

    Chida, Noritaka

    Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

  3. Synthesis of the C(18) -norditerpenoid alkaloid neofinaconitine: a lesson in convergent synthesis planning.

    Science.gov (United States)

    Liu, Xiao-Yu; Chen, David Y-K

    2014-01-20

    Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.

  4. Stereoselective synthesis of enantiomerically pure nupharamine alkaloids from castoreum.

    Science.gov (United States)

    Stoye, Alexander; Quandt, Gabriele; Brunnhöfer, Björn; Kapatsina, Elissavet; Baron, Julia; Fischer, André; Weymann, Markus; Kunz, Horst

    2009-01-01

    An animalic note: The first total synthesis of the all-cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich-Michael reaction of N-galactosylfurylaldimine to give 1 (Piv = pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.

  5. Total syntheses of indolactam alkaloids (-)-indolactam V, (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2.

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    Nathel, Noah F Fine; Shah, Tejas K; Bronner, Sarah M; Garg, Neil K

    2014-06-01

    We report the total syntheses of (-)-indolactam V and the C7-substituted indolactam alkaloids (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2. The strategy for preparing indolactam V relies on a distortion-controlled indolyne functionalization reaction to establish the C4-N linkage, in addition to an intramolecular conjugate addition to build the conformationally-flexible nine-membered ring. The total synthesis of indolactam V then sets the stage for the divergent synthesis of the other targeted alkaloids. Specifically, late-stage sp(2)-sp(3) cross-couplings on an indolactam V derivative are used to introduce the key C7 substituents and the necessary quaternary carbons. These challenging couplings, in addition to other delicate manipulations, all proceed in the presence of a basic tertiary amine, an unprotected secondary amide, and an unprotected indole. Thus, our approach not only enables the enantiospecific total syntheses of four indolactam alkaloids, but also serves as a platform for probing complexity-generating and chemoselective transformations in the context of alkaloid total synthesis.

  6. Synthesis of Morphinan Alkaloids in Saccharomyces cerevisiae.

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    Elena Fossati

    Full Text Available Morphinan alkaloids are the most powerful narcotic analgesics currently used to treat moderate to severe and chronic pain. The feasibility of morphinan synthesis in recombinant Saccharomyces cerevisiae starting from the precursor (R,S-norlaudanosoline was investigated. Chiral analysis of the reticuline produced by the expression of opium poppy methyltransferases showed strict enantioselectivity for (S-reticuline starting from (R,S-norlaudanosoline. In addition, the P. somniferum enzymes salutaridine synthase (PsSAS, salutaridine reductase (PsSAR and salutaridinol acetyltransferase (PsSAT were functionally co-expressed in S. cerevisiae and optimization of the pH conditions allowed for productive spontaneous rearrangement of salutaridinol-7-O-acetate and synthesis of thebaine from (R-reticuline. Finally, we reconstituted a 7-gene pathway for the production of codeine and morphine from (R-reticuline. Yeast cell feeding assays using (R-reticuline, salutaridine or codeine as substrates showed that all enzymes were functionally co-expressed in yeast and that activity of salutaridine reductase and codeine-O-demethylase likely limit flux to morphine synthesis. The results of this study describe a significant advance for the synthesis of morphinans in S. cerevisiae and pave the way for their complete synthesis in recombinant microbes.

  7. Total Synthesis of (-)-Conolutinine.

    Science.gov (United States)

    Feng, Xiangyang; Jiang, Guangde; Xia, Zilei; Hu, Jiadong; Wan, Xiaolong; Gao, Jin-Ming; Lai, Yisheng; Xie, Weiqing

    2015-09-18

    The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

  8. 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.

  9. Total Synthesis of Naloxone

    Institute of Scientific and Technical Information of China (English)

    HU Wen-Xiang; WANG Jian-Ying; XU Ming

    2003-01-01

    @@ Naloxone (1) is one of the 14-hydroxyl substituted opium antagonists which are valuable medications for treat ment of opiate abuse, opiate overdose, and alcohol addiction. Here, the total synthesis of naloxone was described. We selected 2,6-dihydroxynaphalene (2) as the starting material.

  10. Molluscicidal acridone alkaloids from Angostura paniculata: isolation, structures, and synthesis.

    Science.gov (United States)

    Vieira, P C; Kubo, I; Kujime, H; Yamagiwa, Y; Kamikawa, T

    1992-08-01

    Two novel acridone alkaloids, cuspanine [1] and cusculine [2], were isolated from the CH2Cl2 extract of the leaves of Angostura paniculata (Rutaceae). Their structures were established as 1-hydroxy-2,3,5,6-tetramethoxy-9-acridone for 1 and 1,2,3,5,6-pentamethoxy-9-acridone for 2 by means of spectroscopic studies, in particular nmr. These structural assignments were confirmed by synthesis, using a direct metallation method as a key reaction. Both alkaloids exhibited moderate molluscicidal activity against an aquatic snail, Biomphalaria glabrata, and cytotoxicity against several types of carcinoma cell lines.

  11. A configurational switch based on iridium-catalyzed allylic cyclization: application in asymmetric total syntheses of prosopis, dendrobate, and spruce alkaloids.

    Science.gov (United States)

    Gnamm, Christian; Brödner, Kerstin; Krauter, Caroline M; Helmchen, Günter

    2009-10-12

    A method for the stereoselective synthesis of 2,6-disubstituted piperidines has been developed that is based on the use of an intramolecular iridium-catalyzed allylic substitution as a configurational switch. The procedure allows the preparation of 2-vinylpiperidines with enantiomeric excesses (ee) of greater than 99%. As applications, total syntheses of piperidine alkaloids have been elaborated, most often by using Ru-catalyzed cross-metatheses as a key step for introduction of a side chain. Asymmetric total syntheses of the prosopis alkaloids (+)-prosopinine, (+)-prosophylline, (+)-prosopine, and of the dendrobate alkaloid (+)-241D and its C6 epimer are described.

  12. 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

    2016-08-01

    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.

  13. Total enantioselective synthesis of (-)-cytisine.

    Science.gov (United States)

    Danieli, Bruno; Lesma, Giordano; Passarella, Daniele; Sacchetti, Alessandro; Silvani, Alessandra; Virdis, Andrea

    2004-02-19

    [reaction: see text] The first total enantiosynthesis of the biologically active alkaloid (-)-cytisine is reported, featuring a ruthenium-catalyzed RCM reaction as the key step. The approach relies on readily available cis-piperidine-3,5-dimethanol monoacetate as the chiral building block, and it is suited for achieving the target compound in both enantiomeric forms.

  14. Asymmetric total synthesis of (-)-lundurine B and determination of its absolute stereochemistry.

    Science.gov (United States)

    Nakajima, Masaya; Arai, Shigeru; Nishida, Atsushi

    2015-04-01

    A total synthesis of the Kopsia tenuis alkaloid (-)-lundurine B has been achieved. A quaternary chiral carbon has been created by an asymmetric deprotonation using a symmetric spiro cyclohexanone intermediate with a chiral lithium amide. The hexacyclic skeleton was sequentially constructed through metal-mediated reactions. The absolute stereochemistry of intermediate 5 has been unambiguously established by X-ray crystallographic analysis. This is the first description of the absolute stereochemistry of Kopsia tenuis alkaloids based on chemical synthesis.

  15. Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives

    Directory of Open Access Journals (Sweden)

    Shaojun Zheng

    2016-09-01

    Full Text Available A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R4 and R5 significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents.

  16. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

    Science.gov (United States)

    Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

    2014-01-01

    To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

  17. The total synthesis of psymberin.

    Science.gov (United States)

    Huang, Xianhai; Shao, Ning; Palani, Anandan; Aslanian, Robert; Buevich, Alexei

    2007-06-21

    The total synthesis of a new member of the pederin family of natural products, psymberin 1, was accomplished. Using a recently reported novel and efficient PhI(OAc)2 mediated oxidative entry to 2-(N-acylaminal)-substituted tetrahydropyrans as the key step, this total synthesis was executed in a convergent and efficient manner. The longest linear sequence of this synthesis was 22 steps starting from known 6.

  18. A convenient microwave-assisted synthesis of cinchona alkaloid-derived ligands

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An efficient synthesis of cinchona alkaloid-derived ligands based on solvent-free microwave-assisted reaction was described. The coupling of 1,4-dichlorophthalazine or 3,6-dichloropyridazine with quinine, cinchonine or cinchonidine provide bis- or mono-cinchona alkaloid-derived ligands in moderate to good yields (52-89%) within 15 rain under optimum microwave conditions.

  19. 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

    and efficient formal total synthesis of the alkaloid (+/-)-perhydrohistrionicotoxin (2). Thus, (+/-)-depentylperhydrohistrionicotoxin, 1, a known key intermediate for the synthesis of 2, was synthesised from 2,3-epoxycyclohexan-1-one in 10 laboratory operations and ca. 20% overall yield. The synthetic route...

  20. [Study on separation and purification of total alkaloids from Macleaya cordata].

    Science.gov (United States)

    Yu, Jian-sheng; Yu, Jian-ping

    2007-08-01

    A method for separation and purification of total alkaloids from Macleaya cordata with macroporous resin was studied, with the content and recovery rate of total alkaloids as indexes. The results were as follows: The static adsorption capacity of AB-8 type resin was 104. 65 mg/g, the static elution ratio were 95.9% , the dynamic adsorption capacity of AB-8 type resin was 96.5 mg/g, the recovery rate was more than 91.24% and the purity was more than 90%. AB-8 type resin was the best for separating and purificating Macleaya cordata in total alkaloids. The optimum conditions is: the eluant is 90% alcohol and 2-3 times as the volume of the resin, the volume of the resin is 10.4 times of total alkaloids in sample, concentration of total alkaloids of sample is 21.57 mg/ml and current velocity of 2-3 ml/min, pH value of sample is 7-8.

  1. Identification of QTLs for resistant starch and total alkaloid content in brown and polished rice.

    Science.gov (United States)

    Zeng, Y W; Sun, D; Du, J; Pu, X Y; Yang, S M; Yang, X M; Yang, T; Yang, J Z

    2016-07-29

    An F3 population consisting of 117 F2:3 families derived from a cross between two varieties of rice, Gongmi No. 3 and Diantun 502, with a large difference in their resistant starch and total alkaloid content, was used for quantitative trait locus (QTL) mapping. Two QTLs of resistant starch for rice (qRS7-1, qRS7-2) were identified in a linkage group on chromosome 7, which could explain phenotypic variance from 7.6 to 17.3%, due to additive effects for resistant starch from Gongmi No. 3 or over-dominance effects for qRS7-2 of the marker interval (RM3404-RM478) on chromosome 7 from Gongmi No. 3, accounting for 13.8-17.3% of the phenotypic variance. Two QTLs of total alkaloids for brown rice (qALb7-1, qALb7-2) were identified in the same linkage group, which could explain phenotypic variance from 7.7 and 19.3%, respectively, due to dominance or over-dominance effects for total alkaloids on chromosome 7 from Diantun 502. To our knowledge, these are the first QTLs to be identified, which are related to resistant starch and total alkaloid content in rice. These results are beneficial for understanding the genetic basis of, as well as for developing markers linked with, resistant starch and total alkaloids of functional components for marker-assisted selection breeding in rice.

  2. [Analysis of effect of topographical conditions on content of total alkaloid in Coptidis Rhizoma in Chongqin, China].

    Science.gov (United States)

    Liu, Xin; Huang, He; Yang, Yan-fang; Wu, He-zhen

    2014-12-01

    To study ecology suitability rank dividing of the total alkaloid content of Coptis Rhizoma for selecting artificial planting base and high-quality industrial raw material in Chongqing province. Based on the investigation of PCB and DEM data of Chongqing province, the relationship between the total alkaloid content in Coptis Rhizoma and topographical conditions was analyzed by statistical analysis. The geographic information systems (GIS)-based assessment and landscape ecological principles were applied to assess eco logy suitability areas of Coptis Rhizoma in Chongqing. slope, aspect and altitude are main topographical factors that affect the content of the total alkaloid content in Coptis Rhizoma The total alkaloid content in Coptis Rhizoma is higher in the lower altitude, shady slope and bigger slope areas. The total alkaloid content is higher in the south areas of Chongqing province and lower in the northeast. Terrain conditions of the southern region of Chongqing are most suitable for The accumulated of total alkaloid Coptis Rhizoma content.

  3. Total synthesis of (+/-)-cytisine.

    Science.gov (United States)

    O'Neill, B T; Yohannes, D; Bundesmann, M W; Arnold, E P

    2000-12-28

    [reaction:see text] The nicotine partial agonist cytisine was prepared in five steps featuring an "in situ" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.

  4. Design, synthesis and decoration of molecular scaffolds for exploitation in the production of alkaloid-like libraries.

    Science.gov (United States)

    Craven, Philip; Aimon, Anthony; Dow, Mark; Fleury-Bregeot, Nicolas; Guilleux, Rachel; Morgentin, Remy; Roche, Didier; Kalliokoski, Tuomo; Foster, Richard; Marsden, Stephen P; Nelson, Adam

    2015-06-01

    The design, synthesis and decoration of six small molecule libraries is described. Each library was inspired by structures embedded in the framework of specific alkaloid natural products. The development of optimised syntheses of the required molecular scaffolds is described, in which reactions including Pd-catalysed aminoarylation and diplolar cycloadditions have been exploited as key steps. The synthesis of selected exemplar screening compounds is also described. In five cases, libraries were subsequently nominated for production on the basis of the scope and limitations of the validation work, as well as predicted molecular properties. In total, the research has led to the successful synthesis of >2500 novel alkaloid-like compounds for addition to the screening collection (the Joint European Compound Library, JECL) of the European Lead Factory.

  5. Efficient enantio- and diastereodivergent synthesis of poison-frog alkaloids 251O and trans-223B.

    Science.gov (United States)

    Toyooka, Naoki; Zhou, Dejun; Nemoto, Hideo; Tezuka, Yasuhiro; Kadota, Shigetoshi; Andriamaharavo, Nirina R; Garraffo, H Martin; Spande, Thomas F; Daly, John W

    2009-09-04

    An efficient and flexible synthesis of poison-frog alkaloids 251O and trans-223B has been achieved by using for both alkaloids an enantiodivergent process starting from the common lactam 1. The relative stereochemistry of 251O and trans-223B was determined to be 7 (R = n-C(7)H(15), R' = n-Pr) and 14 by the present enantioselective synthesis.

  6. Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and benzylisoquinoline alkaloids.

    Science.gov (United States)

    Schrittwieser, Joerg H; Resch, Verena; Wallner, Silvia; Lienhart, Wolf-Dieter; Sattler, Johann H; Resch, Jasmin; Macheroux, Peter; Kroutil, Wolfgang

    2011-08-19

    A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.

  7. Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

    Science.gov (United States)

    2011-01-01

    A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C–C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4–8 linear steps using either a Bischler–Napieralski cyclization or a C1–Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5–9 linear steps. PMID:21739961

  8. 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.

  9. 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].

  10. 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.

  11. 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.

  12. 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

  13. The total synthesis of (-)-nitidasin.

    Science.gov (United States)

    Hog, Daniel T; Huber, Florian M E; Mayer, Peter; Trauner, Dirk

    2014-08-01

    Nitidasin is a pentacyclic sesterterpenoid with a rare 5-8-6-5 carbon skeleton that was isolated from the Peruvian folk medicine "Hercampuri". It belongs to a small class of sesterterpenoids that feature an isopropyl trans-hydrindane moiety fused to a variety of other ring systems. As a first installment of our general approach toward these natural products, we report the total synthesis of the title compound. Our stereoselective, convergent route involves the addition of a complex alkenyl lithium compound to a trans-hydrindanone, followed by chemoselective epoxidation, ring-closing olefin metathesis, and redox adjustment.

  14. 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...

  15. The quest for a practical synthesis of morphine alkaloids and their derivatives by chemoenzymatic methods.

    Science.gov (United States)

    Reed, Josephine W; Hudlicky, Tomas

    2015-03-17

    We became interested in approaches to morphine in the early 1990s following our immersion into the new program on the enzymatic dihydroxylation of aromatics. Larry Kwart, a former classmate of one of us at Rice University, who worked with our group at Virginia Tech in the mid-1980s, introduced to us the use of blocked mutants of Pseudomonas putida (Pp39D) for the production of arene-cis-dihydrodiols. Larry had gained expertise in microbiology from a postdoctoral stay with David Gibson, who discovered this unique enzymatic transformation, and he helped us to establish a strong program in chemoenzymatic synthesis that continues to this day. Without his pioneering effort, none of our accomplishments in chemoenzymatic synthesis, including the various approaches to morphine, would have materialized. Here we trace the evolution of our approaches to morphine alkaloids and some commercial opiate-derived medicinal agents. The design features and chronology of our approaches are discussed in a way that allows the reader to appreciate a number of errors that were made in conception as well as in execution. Experience acquired from many failed or less-than-effective attempts has finally led to an "almost reasonable" total synthesis, the key concept being based on our very first but unsuccessful attempt more than two decades ago. The irony of this accomplishment has not been lost on us. Each section of this Account presents a summary of distinctly different approaches to morphine alkaloids. Each ends with a short and philosophical lesson that was (or should have been) learned in the process. We intend for this Account to offer more than the history of a search for the perfect design solution to a synthetic problem. In today's era of rapid and often careless publication of results, it should serve also as a reminder that the success and the integrity of synthetic ventures depends on perseverance, adjustment of strategy, improvements of previous attempts, and serious attention to

  16. 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...... alkaloid was prepared from antirrhinoside by means of an enzymatic cleavage to afford the aglucone, followed by a double reductive amination with benzylamine hydrochloride and sodium cyanoborohydride. The resulting piperidine was modified by opening of the epoxide on the cyclopropane ring by azide...... strategy was therefore abandoned.A one-pot reaction involving ozonolysis and subsequent reduction of the 5,6-O-isopropylidene-2',3',4',6'-tetra-O-acetyl antirrhinoside yielded a diol, which was considered a potential intermediate in the preparation of enantiopure 3-azabicyclo[3.3.0]octane alkaloids...

  17. The Diaza[5.5.6.6]fenestrane Skeleton-Synthesis of Leuconoxine Alkaloids.

    Science.gov (United States)

    Pfaffenbach, Magnus; Gaich, Tanja

    2016-03-07

    Among the Aspidosperma-derived monoterpene indole alkaloids, the leuconoxine subgroup has drawn significant attention from the synthetic community during the past few years. This Minireview summarizes the hitherto six completed total syntheses of leuconoxines emphasizing the different strategies for assembling the key structural motif, an unprecedented diaza[5.5.6.6]fenestrane skeleton. In addition, the proposed biogenetic relationships within the group of these alkaloids are described.

  18. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A.; Borch, Morten

    2013-01-01

    The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype...

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

    Science.gov (United States)

    Weinreb, Steven M

    2003-01-01

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

  20. A Concise Synthesis of Monoterpene Pyridine Alkaloid Aucubinine B

    Institute of Scientific and Technical Information of China (English)

    杨晓霞; 赵景瑞; 贾学顺; 杨力维; 翟宏斌

    2003-01-01

    Aucubinine B (4), a monoterpene alkaloid obtained from the metabolites of aucubin in the presence of human intestinal bacteria, has been synthesized from 3-bromo-4-pyridinecarboxaldehyde (5) in four steps with 39% overall yield. The construction of the cyclopenta[c]pyridine intermediate (7) was realized by an intramolecular Heck reaction.

  1. The total alkaloid and anagyrine contents of some bitter and sweet selections of lupin species used as food.

    Science.gov (United States)

    Keeler, R F; Gross, R

    1980-01-01

    The total alkaloid and anagyrine contents of bitter and sweet Lupinus luteus, Lupinus angustifolius, Lupinus albus, Lupinus mutabilis, Lupinus polyphyllus, and Lupinus perennis were analyzed by gas chromatography (GC) and mass spectrometry. No anagyrine was detected in any of the samples. The GC peak in some of the samples which corresponded to anagyrine in retention of time seems to be identical to 17-oxolupanine. The alkaloid content of samples ranged from 3.17 to 0.003 percent.

  2. Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

    Science.gov (United States)

    Mohamed, A F; Matsumoto, K; Tabata, K; Takayama, H; Kitajima, M; Watanabe, H

    2000-12-01

    The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

  3. Recent advances in isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids of marine origin.

    Science.gov (United States)

    Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E

    2015-08-01

    The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine, have been isolated from various marine organisms. A class of pyrroloiminoquinone-related alkaloids, known as bispyrroloquinones, is the focus of this review article. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B, and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogs show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogs that has been discovered recently is through the inhibition of indoleamine 2, 3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids and their analogs.

  4. Solid-phase synthesis and chemical space analysis of a 190-membered alkaloid/terpenoid-like library

    OpenAIRE

    Moura-Letts, Gustavo; DiBlasi, Christine M.; Bauer, Renato A.; Tan, Derek S.

    2011-01-01

    Alkaloid and terpenoid natural products display an extensive array of chemical frameworks and biological activities. However such scaffolds remain underrepresented in current screening collections and are, thus, attractive targets for the synthesis of natural product-based libraries that access underexploited regions of chemical space. Recently, we reported a systematic approach to the stereoselective synthesis of multiple alkaloid/terpenoid-like scaffolds using transition metal-mediated cycl...

  5. Asymmetric total synthesis of vindoline.

    Science.gov (United States)

    Kato, Daisuke; Sasaki, Yoshikazu; Boger, Dale L

    2010-03-24

    A concise asymmetric total synthesis of (-)-vindoline (1) is detailed based on a tandem intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which the tether linking the initiating dienophile and oxadiazole bears a chiral substituent that controls the facial selectivity of the initiating Diels-Alder reaction and sets absolute stereochemistry of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduces three rings and four C-C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. Implementation of the approach also required the development of a unique ring expansion reaction to provide a six-membered ring suitably functionalized for introduction of the Delta (6, 7)-double bond found in the core structure of vindoline and defined our use of a protected hydroxymethyl group as the substituent used to control the stereochemical course of the cycloaddition cascade.

  6. A General, Concise Strategy that Enables Collective Total Syntheses of over 50 Protoberberine and Five Aporhoeadane Alkaloids within Four to Eight Steps.

    Science.gov (United States)

    Zhou, Shiqiang; Tong, Rongbiao

    2016-05-17

    A concise, catalytic, and general strategy that allowed efficient total syntheses of 22 natural 13-methylprotoberberines within four steps for each molecule is reported. This synthesis represents the most efficient and shortest route to date, featuring three catalytic processes: CuI-catalyzed redox-A(3) reaction, Pd-catalyzed reductive carbocyclization, and PtO2 -catalyzed hydrogenation. Importantly, this new strategy to the tetracyclic framework has also been applied to the collective concise syntheses of >30 natural protoberberines (without 13-methyl group) and five aporhoeadane alkaloids.

  7. 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.

  8. "Scolicidal effect of alcoholic, aqueous and total alkaloids of Peganum Harmala L. (Syrian Rue against hydatid cysts protoscolices "

    Directory of Open Access Journals (Sweden)

    Mahdavi M

    2002-08-01

    Full Text Available Introduction: Alcoholic and aqueous extracts and total alkaloids of the seed of (Syrian rue peganum harmala L. as scolicidal compound against Hydatid cyst protoscolices were assessed in this study. Methods and Materials: This study was carried out both invitro and by inoculating inside the intact cysts in the shaking bath and dry incubator at 37°c. Different concentration of suspensions were tested in different exposure times. Mortality of protoscolices was determined by their loss of mortality, ability to take vital stains and inactivity of flame cells. Results: The results indicated that alcoholic extract had scolicidal effect against protoscolices; total alkaloids had stronger action and rapid effect on protoscolices.

  9. Synthesis of (R-Dihydropyridones as Key Intermediates for an Efficient Access to Piperidine Alkaloids

    Directory of Open Access Journals (Sweden)

    Serkos A Haroutounian

    2007-04-01

    Full Text Available The efficient transformation of D-glucal to (2R-hydroxymethyldihydro-pyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+-desoxoprosophylline (1 and deoxymannojirimycin (3 or D-mannolactam (4, respectively.

  10. Cyclobutane Synthesis and Fragmentation. A Cascade Route to the Lycopodium Alkaloid (-)-Huperzine A.

    Science.gov (United States)

    White, James D; Li, Yang; Kim, Jungchul; Terinek, Miroslav

    2015-12-04

    An asymmetric total synthesis of the nootropic alkaloid (-)-huperzine A was completed using a cascade sequence initiated by an intramolecular aza-Prins reaction and terminated by a stereoelectronically guided fragmentation of a cyclobutylcarbinyl cation as the key step in assembling the bicyclo[3.3.1]nonene core of the natural product. Intramolecular [2 + 2]-photocycloaddition of the crotyl ether of (S)-4-hydroxycyclohex-2-enone afforded a bicyclo[4.2.0]octanone containing an embedded tetrahydrofuran in which the cyclohexanone moiety was converted to a triisopropylsilyl enol ether and functionalized as an allylic azide. The derived primary amine was acylated with α-phenylselenylacrylic acid, and the resulting amide was reacted with trimethylaluminum to give a [2 + 2]-cycloadduct, which underwent retroaldol fission to produce a fused α-phenylselenyl δ-lactam. Periodate oxidation of this lactam led directly to an α-pyridone, which was converted to a fused 2-methoxypyridine. Reductive cleavage of the activated "pyridylic" C-O bond in this tetracycle and elaboration of the resultant hydroxy ketone to a diketone was followed by chemoselective conversion of the methyl ketone in this structure to an endo isopropenyl group. Condensation of the remaining ketone with methyl carbamate in the presence of acid initiated the programmed cascade sequence and furnished a known synthetic precursor to huperzine A. Subsequent demethylation of the carbamate and the methoxypyridine, accompanied by in situ decarboxylation of the intermediate carbamic acid, gave (-)-huperzine A.

  11. 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.

  12. Horizontal acquisition of toxic alkaloid synthesis in a clade of plant associated fungi.

    Science.gov (United States)

    Marcet-Houben, Marina; Gabaldón, Toni

    2016-01-01

    Clavicipitaceae is a fungal group that comprises species that closely interact with plants as pathogens, parasites or symbionts. A key factor in these interactions is the ability of these fungi to synthesize toxic alkaloid compounds that contribute to the protection of the plant host against herbivores. Some of these compounds such as ergot alkaloids are toxic to humans and have caused important epidemics throughout history. The gene clusters encoding the proteins responsible for the synthesis of ergot alkaloids and lolines in Clavicipitaceae have been elucidated. Notably, homologs to these gene clusters can be found in distantly related species such as Aspergillus fumigatus and Penicillium expansum, which diverged from Clavicipitaceae more than 400 million years ago. We here use a phylogenetic approach to analyze the evolution of these gene clusters. We found that the gene clusters conferring the ability to synthesize ergot alkaloids and loline emerged first in Eurotiomycetes and were then likely transferred horizontally to Clavicipitaceae. Horizontal gene transfer is known to play a role in shaping the distribution of secondary metabolism clusters across distantly related fungal species. We propose that HGT events have played an important role in the capability of Clavicipitaceae to produce two key secondary metabolites that have enhanced the ability of these species to protect their plant hosts, therefore favoring their interactions.

  13. 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.

  14. 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;

    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...... copper(I) chloride and lithium chloride was found to be most efficient. The methodology was successfully applied to join two major fragments of the zoanthamine skeleton. (c) 2005 Elsevier Ltd. All rights reserved....

  15. 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)....

  16. Total Synthesis of (±)-Celaphanol A

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The first total synthesis of (±)-Celaphanol A was accomplished starting from α-cyclocitral and 3,4-dimethoxy benzyl chloride via a six-step process, in which the intramolecular cyclization of ketone 4 with BF3@Et2O afforded an all-cis isomer intermediate for synthesis of aromatic tricyclic diterpenes.

  17. 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).

  18. A modified total synthesis of cystothiazole A

    Institute of Scientific and Technical Information of China (English)

    BAI YueXia; BAO JiLai; REN Jun; WANG ZhongWen

    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).

  19. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine.

    Science.gov (United States)

    Winzer, Thilo; Gazda, Valeria; He, Zhesi; Kaminski, Filip; Kern, Marcelo; Larson, Tony R; Li, Yi; Meade, Fergus; Teodor, Roxana; Vaistij, Fabián E; Walker, Carol; Bowser, Tim A; Graham, Ian A

    2012-06-29

    Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F(2) mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.

  20. 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.

  1. A Convergent Total Synthesis of Methoxatin

    NARCIS (Netherlands)

    Hendrickson, James B.; Vries, Johannes G. de

    1982-01-01

    We report a convergent total synthesis of the coenzyme methoxatin (1) by linking a pyrrole subunit with an uvitonic acid derivative and oxidative photocyclization to a deoxymethoxatin triester, followed by seven refunctionalization steps to 1.

  2. Pyrrolizidine alkaloids.

    Science.gov (United States)

    Robertson, Jeremy; Stevens, Kiri

    2014-12-01

    This review covers pyrrolizidine alkaloids isolated from natural sources. Topics include: aspects of structure, isolation, and biological/pharmacological studies; total syntheses of necic acids, necine bases and closely-related non-natural analogues.

  3. 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.

  4. 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.

  5. A concise synthesis of (R)-Bgugaine, a pyrrolidine alkaloid from Arisarum vulgare

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Parameswaran, P.S.; Tilve, S.G.

    and effective chiral catalysts. 2-4 There are a large number of studies concerning the development of new syntheses of these molecules. 5-7 (R)-Bgugaine (1) is a natural 2-alkyl pyrrolidine alkaloid, first isolated 8 in 1993 from the tubers... potent hepatotoxin in rat and human liver cells and induces significant DNA damage in a human hepatoblastoma (HepG 2 ) cell line. 12 So far, three syntheses of (R)-Bgugaine (1) have been reported. The first synthesis of 1 by Jossang et. al...

  6. 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 .

  7. A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine

    Science.gov (United States)

    Lebold, Terry P.; Wood, Jessica L.; Deitch, Josh; Lodewyk, Michael W.; Tantillo, Dean J.; Sarpong, Richmond

    2013-02-01

    The yohimbinoid alkaloids continue to receive considerable attention from the synthetic community because of their interesting chemical structures and varied biological activity. Although there are several elegant syntheses of certain members of this group of alkaloids, a truly unified approach has yet to be developed. In short, general approaches to this compound class are hampered by a lack of complete control in setting the C(3) stereocentre at a late stage. Herein, we report that a functionalized hydrindanone enables a divergent strategy that builds on existing precedent to address this long-standing challenge. Utilizing an aminonitrile intermediate, the stereochemistry at C(3) of the yohimbinoid skeleton can be controlled effectively in a Pictet-Spengler reaction. We applied this approach to the first total syntheses of the C(3) epimeric natural products venenatine and alstovenine.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Fang; Wang Changhong; Xiong Aizhen; Wang Wan; Yang Li [Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Zhangjiang Hi-Tech Park, Shanghai 201203 (China); Branford-White, Christopher J. [Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road, London N7 8DB (United Kingdom); Wang Zhengtao [Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Zhangjiang Hi-Tech Park, Shanghai 201203 (China); School of Chinese Pharmacy, China Pharmaceutical University, Nanjing 210038 (China)], E-mail: wangzt@shutcm.edu.cn; Bligh, S.W. Annie [Institute for Health Research and Policy, London Metropolitan University, 166-220 Holloway Road, London N7 8DB (United Kingdom)], E-mail: a.bligh@londonmet.ac.uk

    2007-12-12

    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{sup -1} and the limit of quantitation is 0.79 nmol mL{sup -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.

  9. 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

  10. 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-o...

  11. Total synthesis of aeruginosin 98B.

    Science.gov (United States)

    Trost, Barry M; Kaneko, Toshiyuki; Andersen, Neil G; Tappertzhofen, Christoph; Fahr, Bruce

    2012-11-21

    The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.

  12. Recent developments in the chemistry of quinazolinone alkaloids.

    Science.gov (United States)

    Kshirsagar, U A

    2015-09-28

    Quinazolinones, an important class of fused heterocyclic alkaloids has attracted high attention in organic and medicinal chemistry due to their significant and wide range of biological activities. There are approximately 150 naturally occurring quinazolinone alkaloids known till 2005. Several new quinazolinone alkaloids (∼55) have been isolated in the last decade. Natural quinazolinones with exotic structural features and remarkable biological activities have incited a lot of activities in the synthetic community towards the development of new synthetic strategies and approaches for the total synthesis of quinazolinone alkaloids. This review is focused on these advances in the chemistry of quinazolinone alkaloids in the last decade. This article covers the newly isolated quinazolinone natural products with their biological activities and the recently reported total syntheses of quinazolinone alkaloids from 2006 to 2015.

  13. Anti-helicobacter pylori effect of total alkaloids of sophora alopecuroides in vivo

    Institute of Scientific and Technical Information of China (English)

    Tian Aiping; Xu Ting; Liu Kaiyun; Zou Quanming; Yan Xiang

    2014-01-01

    Background Helicobacterpylori (H.pylori) infection could lead to most gastroduodenal diseases and is even identified as a carcinogen of gastric cancer.Total alkaloids of sophora alopecuroides (TASA) is widely used in herbal remedies to treat various infectious diseases,including stomach-associated diseases.This study is aimed at evaluating the antimicrobial activity of TASA on H.pylori-infected BALB/c mice mouse gastritis.Methods Totally 120 BALB/c mice were orally inoculated with H.pylori Bacterial liquid to construct BALB/c mice H.pylori infection gastritis animal model,after the model was successfully created.We randomly assigned 100 infected mice into 10 treatment groups,the first group (normal saline); the second group (bismuth pectin); the third group (omeprazole); the fourth group (TASA 2 mg/d); the fifth group (TASA 4 mg/d); the sixth group (TASA 5 mg/d); the seventh group (TASA + bismuth pectin); the eighth group (TASA + omeprazole); the ninth group (bismuth pectin + clarithromycin + metronidazole);the tenth group (omeprazole + clarithromycin + metronidazole),5 other non-infected mice as negative control.Mice were orally inoculated twice a day and 7 days continuously.Then the mice were killed 4 weeks after treatment,we used realtime PCR to detect 16sDNA of H.pylori to test both the colonization and the clearance mice of bacteria of each treatment.We applied hematoxylin and eosin (HE) staining and immunostaining of mice gastric mucosa to observe the general inflammation and related factors interleukin 8 (IL-8),cyclooxygenase 2 (COX-2),and nuclear factor-kappa B (NF-KB) expression change after treatments.Results Firstly,we ensured that after 6-week intragastric administration,the bacteria colonization reached an exceed peak which is far higher than positive threshold (P <0.001); secondly,after treatments,it is revealed that TASA combined with omeprazole or bismuth pectin showed promising antimicrobial activity against H.pylori as well as conventional

  14. New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids.

    Science.gov (United States)

    Plodek, Alois; Bracher, Franz

    2016-01-26

    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.

  15. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    Science.gov (United States)

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

    2014-12-01

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

  16. Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

    Directory of Open Access Journals (Sweden)

    Gaetan eMaertens

    2015-01-01

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

  17. Total synthesis of mangiferin, homomangiferin, and neomangiferin.

    Science.gov (United States)

    Wei, Xiong; Liang, Danlin; Wang, Qing; Meng, Xiangbao; Li, Zhongjun

    2016-09-21

    Total synthesis of mangiferin, homomangiferin, and neomangiferin, three C-glycosyl xanthone natural products with a wide spectrum of pharmacological effects, has been achieved starting from 2,3,4,6-tetra-O-benzyl-α/β-d-glucopyranose. The key steps involve a stereoselective Lewis acid promoted C-glycosylation of protected phloroglucinol with tetrabenzylglucopyranosyl acetate and a highly regioselective base-induced cyclization for the construction of the core xanthone skeleton.

  18. 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

  19. Total synthesis and biological investigation of (-)-promysalin.

    Science.gov (United States)

    Steele, Andrew D; Knouse, Kyle W; Keohane, Colleen E; Wuest, William M

    2015-06-17

    Compounds that specifically target pathogenic bacteria are greatly needed, and identifying the method by which they act would provide new avenues of treatment. Herein we report the concise, high-yielding total synthesis (eight steps, 35% yield) of promysalin, a natural product that displays antivirulence phenotypes against pathogenic bacteria. Guided by bioinformatics, four diastereomers were synthesized, and the relative and absolute stereochemistries were confirmed by spectral and biological analysis. Finally, we show for the first time that promysalin displays two antivirulence phenotypes: the dispersion of mature biofilms and the inhibition of pyoverdine production, hinting at a unique pathogenic-specific mechanism of action.

  20. Total Synthesis of (-)-Salvinorin A.

    Science.gov (United States)

    Line, Nathan J; Burns, Aaron C; Butler, Sean C; Casbohm, Jerry; Forsyth, Craig J

    2016-12-12

    Salvinorin A (1) is natural hallucinogen that binds the human κ-opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l-(+)-tartaric acid into that of (-)-1 via an unprecedented allylic dithiane intramolecular Diels-Alder reaction to obtain the trans-decalin scaffold. Tsuji allylation set the C9 quaternary center and a late-stage stereoselective chiral ligand-assisted addition of a 3-titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto-acetate.

  1. Toward Total Synthesis of Yohimbine and Reserpine Alkaloids; Part 1.An Improved Synthesis of cis-5, 8-Dihydroxy-1, 4, 5, 8, 9,10-hexahydronaphthalene-1, 8-lactone via Selective Reduction of the Conjugated Ketone with Zn (BH4)2

    Institute of Scientific and Technical Information of China (English)

    Yong Ye LI; Mei XU; Fen Er CHEN

    2004-01-01

    An improved and high-yielding synthesis of cis-5, 8-dihydroxy-1, 4, 5, 8, 9, 10- hexa-hydronaphthalene-1,8-lactone 7, an intermediate for (-)-reserpine 1 is presented. The conjugated ketone 5 was regioselectively reduced to afford lactone 7 with zinc borohydride formed in situ from KBH4 and ZnCl2 in THF.

  2. The alkaloids of the madangamine group.

    Science.gov (United States)

    Amat, Mercedes; Pérez, Maria; Ballette, Roberto; Proto, Stefano; Bosch, Joan

    2015-01-01

    This chapter is focused on madangamines, a small group of complex diamine alkaloids isolated from marine sponges of the order Haplosclerida, and covers their isolation, characterization, biogenesis, biological activity, and synthesis. Structurally, madangamines are pentacyclic alkaloids with an unprecedented skeletal type, characterized by a common diazatricyclic core and two peripheral macrocyclic rings. The isolation of these alkaloids from Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera (madangamine F) is described in detail. Physical and complete spectroscopic 1H and 13C NMR data are included. The proposed biogenesis of madangamines from ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is discussed. The synthesis of alkaloids of the madangamine group has been little explored, with only one total synthesis reported so far, that of (+)-madangamine D. This review also describes several model synthetic approaches to the diazatricyclic ABC core of these alkaloids, as well as model studies on the construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this group have shown significant in vitro cytotoxicity against a number of cancer cell lines.

  3. Solid-phase synthesis and chemical space analysis of a 190-membered alkaloid/terpenoid-like library.

    Science.gov (United States)

    Moura-Letts, Gustavo; Diblasi, Christine M; Bauer, Renato A; Tan, Derek S

    2011-04-26

    Alkaloid and terpenoid natural products display an extensive array of chemical frameworks and biological activities. However such scaffolds remain underrepresented in current screening collections and are, thus, attractive targets for the synthesis of natural product-based libraries that access underexploited regions of chemical space. Recently, we reported a systematic approach to the stereoselective synthesis of multiple alkaloid/terpenoid-like scaffolds using transition metal-mediated cycloaddition and cyclization reactions of enyne and diyne substrates assembled on a tert-butylsulfinamide lynchpin. We report herein the synthesis of a 190-membered library of alkaloid/terpenoid-like molecules using this synthetic approach. Translation to solid-phase synthesis was facilitated by the use of a tert-butyldiarylsilyl (TBDAS) linker that closely mimics the tert-butyldiphenysilyl protecting group used in the original solution-phase route development work. Unexpected differences in stereoselectivity and regioselectivity were observed in some reactions when carried out on solid support. Further, the sulfinamide moiety could be hydrolyzed or oxidized efficiently without compromising the TBDAS linker to provide additional amine and sulfonamide functionalities. Principal component analysis of the structural and physicochemical properties of these molecules confirmed that they access regions of chemical space that overlap with bona fide natural products and are distinct from areas addressed by conventional synthetic drugs and drug-like molecules. The influences of scaffolds and substituents were also evaluated, with both found to have significant impacts on location in chemical space and three-dimensional shape. Broad biological evaluation of this library will provide valuable insights into the abilities of natural product-based libraries to access similarly underexploited regions of biological space.

  4. 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.

  5. Treatment of Nonalcoholic Fatty Liver Disease with Total Alkaloids in Rubus aleaefolius Poir through Regulation of Fat Metabolism

    Directory of Open Access Journals (Sweden)

    Ying Li

    2014-01-01

    Full Text Available Total alkaloids in Rubus aleaefolius Poir (TARAP is a folk medicinal herb that has been used clinically in China to treat nonalcoholic fatty liver disease (NAFLD for many years. However, the mechanism of its anti-NAFLD effect is largely unknown. In this study, we developed a NAFLD rat model by supplying a modified high-fat diet (mHFD ad libitum for 8 weeks and evaluated the therapeutic effect of TARAP in NAFLD rats as well as the underlying molecular mechanism. We found that TARAP could reduce the serum triglycerides (TG, total cholesterol (TC, and low-density lipoprotein (LDL-C levels and increase the serum high-density lipoprotein (HDL-C level in NAFLD rats. In addition, TARAP treatment reduced expression of fatty acid synthetase (FAS, and acetyl-CoA carboxylase (ACC and upregulated the expression of carnitine palmitoyltransferase (CPT. Our results suggest that regulation of lipid metabolism may be a mechanism by which TARAP treats NAFLD.

  6. Total synthesis of cyclic heptapeptide euryjanicin B

    Institute of Scientific and Technical Information of China (English)

    Chun Mei Zhang; Jun Xiang Guo; Liang Wang; Xiao Yun Chai; Hong Gang Hu; Qiu Ye Wu

    2011-01-01

    The first synthesis of the naturally occurring cyclic peptide euryjanicin B has been achieved. A general method was described to synthesize the cyclic peptide by a two-step solid-phase/solution synthesis strategy. All the amino acids in this study are L-configuration, The linear heptapeptide was assembled by standard Fmoc chemistry on solid-phase and subsequently cyclization was carried out by solution method.

  7. 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.

  8. Synthesis, toxicity study and anti-inflammatory effect of MHTP, a new tetrahydroisoquinoline alkaloid.

    Science.gov (United States)

    Pacheco de Oliveira, Maria Talita; de Oliveira Ramalho, Theresa Raquel; Paiva Ferreira, Laércia Karla Liege; Araújo Lima, Ana Luísa; Barbosa Cordeiro, Manuela; Ferreira Costa, Hermann; Rodrigues, Luís Cézar; Piuvezam, Marcia Regina

    2015-01-01

    The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol (MHTP) was synthesized to prospect new compounds with therapeutic properties. Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP pre-treatment (2.5-10 mg/kg) showed antiedematogenic effect (p alkaloid also reduced (p alkaloid, MHTP has anti-inflammatory effect by inhibiting PGE2 function as well as inhibiting inflammatory cell migration to the inflamed site and attenuated the acute lung injury disease by inhibiting the migration of neutrophil to the lung. However, further studies will be carried out to demonstrate the mechanisms of action of the molecule and explore its potential as a future drug to treat inflammatory processes.

  9. A General Approach to the Quinolizidine Alkaloids via an Intramolecular Aza-[3 + 3] Annulation. Synthesis of (±)-2-Deoxy-Lasubine II.

    Science.gov (United States)

    Zhang, Yu; Gerasyuto, Aleksey I; Long, Quincy A; Hsung, Richard P

    2008-01-01

    The first success in constructing a member of quinolizidine family of alkaloids employing an intramolecular aza-[3 + 3] annulation strategy is described here. The key feature is the usage of vinylogous urethane tethered to a vinyl iminium intermediate with trifluoroacetate serving as the counter anion. The proof-of-concept is illustrated with the synthesis of 2-deoxy-lasubine II.

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

    Science.gov (United States)

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

    2016-04-15

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

  11. Recruiting the Students to Fight Cancer: Total Synthesis of Goniothalamin

    Science.gov (United States)

    Nahra, Fady; Riant, Olivier

    2015-01-01

    A modified total synthesis of (S)-goniothalamin is described for an advanced course in organic chemistry. This experiment gives students an opportunity to handle organometallic reagents and perform an enzymatic kinetic resolution and a metathesis reaction, all in the same synthesis. Furthermore, students learn flame-drying techniques for the…

  12. Total synthesis of the potent microtubule-stabilizing agent (+)-discodermolide.

    Science.gov (United States)

    Harried, Scott S; Lee, Christopher P; Yang, Ge; Lee, Tony I H; Myles, David C

    2003-08-22

    The total synthesis of the potent microtubule-stabilizing, antimitotic agent (+)-discodermolide is described. The convergent synthetic strategy takes advantage of the diastereoselective alkylation of a ketone enolate to establish the key C15-C16 bond. The synthesis is amenable to preparation of gram-scale quantities of (+)-discodermolide and analogues.

  13. Total Synthesis of Mycalolides A and B through Olefin Metathesis.

    Science.gov (United States)

    Kita, Masaki; Oka, Hirotaka; Usui, Akihiro; Ishitsuka, Tomoya; Mogi, Yuzo; Watanabe, Hidekazu; Tsunoda, Masaki; Kigoshi, Hideo

    2015-11-16

    An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.

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

    DEFF Research Database (Denmark)

    Yohannes, Daniel; Hansen, Camilla Petrycer; Akireddy, Srinivasa Rao;

    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 proposed...

  15. The Total Synthesis of 14-Deoxycrassin and Pseudoplexaurol: A Convergent Synthesis of Cyclization Precursor

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The synthesis of epoxy aldehyde 4, a cyclization precursor for the total synthesis of 14-deoxycrassin and pseudoplexaurol, starting from geraniol in a convergent and stereoselective manner, is described.

  16. Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal activity

    NARCIS (Netherlands)

    Rodenko, B.; Al-Salabi, M.I.; Teka, I.A.; Ho, W.; El-Sabbagh, N.; Ali, J.A.M.; Ibrahim, H.M.S.; Wanner, M.J.; Koomen, G.J.; de Koning, H.P.

    2011-01-01

    Given the pressing need for new antiprotozoal drugs without cross-resistance with current (failing) chemotherapy, we have explored 3-tridecylpyridinium alkaloids (3TPAs), derivatives of viscosamine, as antiparasitic agents. We have developed a simple synthetic route toward viscosamine and related cy

  17. Effects of Total Alkaloids in Buxus microphylla Leaves on Aorta Smooth Muscle of Rats and Their Mechanisms

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui-qin; LIU Yan-yan; LI Yong-wen; LI Li; CUI Zhi-qing

    2012-01-01

    Objective To investigate the effects of total alkaloids in Buxus microphylla leaves (ABML) on isolated rats thoracic aorta rings,and then to explore the possible mechanisms underlying the effects.Methods Thoracic aortas of Wistar rats were isolated,removed,and mounted onto an organ bath.The effects of ABML at different concentration on the contraction of isolated thoracic aorta rings (with and without endothelium) precontracted with KC1 or PE were observed with organ bath technique.Dose-effect curves of CaCl2 were recorded by organ bath technique.The concentration of intracellular Ca2+ ([Ca2+]i) increased by PE,KCI,and caffeine in the presence of ABML was determined using Ca2+ sensitive fluorescence indicator Fura-2/AM loaded thoracic aorta vascular smooth muscle (VSM) cells of rats.Results In aorta rings precontracted with PE and KCI,ABML produced concentrationdependent relaxation in both intact and denuded endothelium ring groups.There was no difference in the inhibition of contraction between the intact and denuded endothelium ring groups at the same concentration.Exposure of isolated thoracic aorta rings to ABML led to a significant reduction in the contracting response induced by CaCI2,and shifted the cumulative concentration-response curves to right.ABML could significantly inhibit the extracellular Ca2+ influx induced by PE and KCI under [Ca2+]0 of 1.5 mmol/L,with inhibitory ratios of 40.2% and 49.9%,respectively.In the case of Ca2+-free,ABML could significantly inhibit the intracellular Ca2+ release induced by PE,with inhibitory ratio of 72.4%.Conclusion ABML relaxes thoracic aorta VSM cells by suppressing influx of extracellular Ca2+ via voltage-dependent Ca2+ channel and receptor-operated Ca2+ channel.

  18. 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 cat...

  19. Total synthesis of the proposed structure of astakolactin

    OpenAIRE

    Takayuki Tonoi; Keisuke Mameda; Moe Fujishiro; Yutaka Yoshinaga; Isamu Shiina

    2014-01-01

    The first total synthesis of the proposed structure of astakolactin, a sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization.

  20. 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

  1. 附子总生物碱的提取工艺研究%Extraction Technology of Total Alkaloids from RADIX ACONITI LATERALIS PRAEPARATA

    Institute of Scientific and Technical Information of China (English)

    刘卓; 晏星; 徐春霞; 袁小红

    2012-01-01

    [目的]研究附子总生物碱的提取工艺,优选最佳提取条件.[方法]以提取率、总生物碱收率和总生物碱纯度为指标,采用单因素试验法,考察提取溶剂、提取方法、提取温度、粉碎度、料液比、提取时间和提取次数对附子中总生物碱提取率的影响,并优选出最佳提取工艺条件.[结果]最佳提取工艺条件为:在15℃条件下,将附子粉按1∶10(g/ml)加入无水乙醇,冷浸3次,每次1d;在此条件下,浸膏得率、总生物碱收率和总生物碱纯度分别为3.15%、0.64%和20.32%.[结论]该方法高效、低毒、经济、操作方便、工艺可控,较适合附子总生物碱的提取和工业化生产.%[ Objective ] To determine the optimal extraction technology of alkaloids from the roots of RADIX ACONITI LATERALIS PRA-EPARATA. [ Method ] Taking extraction rate, and the purity and yield of total alkaloid as the indices, effects of extraction solvent, extraction method, extraction temperature, extraction time ,comminution degree, solid-liquid ratio and extraction times on the extraction rate of total alka-loids were studied. And the optimal extraction technology was selected. [ Conclusion ] The optimal extraction technology was as follows : RADIXACONITI LATERALIS PRAEPARATA powder was added into anhydrous alcohol with the ratio of 1:10 (g/mt)under 15 ℃. After cold leaching for 3 times with each time for 1 d, the dry extract rate, extraction rate of total alkaloid, and purity of total alkaloid were 3.15% ,0.64% and 20. 32% ,respectively. [ Conclusion] This method was efficient,low toxic, economical,convenient and can be used for industrial production.

  2. Total synthesis: Towards artificial terpene cyclases

    Science.gov (United States)

    Willot, Matthieu; Christmann, Mathias

    2010-07-01

    The plant-derived sesquiterpene englerin A is a potent inhibitor of several renal cancer cell lines. Two recent total syntheses have utilized cationic gold(I)-complexes to coax readily available open-chain precursors into englerin's challenging oxotricyclic core with enzyme-like precision.

  3. 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.

  4. 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.

  5. 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.

  6. Preparation and in vitro evaluation of ethosomal total alkaloids of Sophora alopecuroides loaded by a transmembrane pH-gradient method.

    Science.gov (United States)

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

    2010-09-01

    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, particle size, and encapsulation efficiency (EE). The percutaneous absorption study of TASA binary ethosomes was performed using confocal laser scanning microscopy and Franz diffusion cells. The results showed that more than 90% sophoridine, 47% matrine, 35% sophocarpine, and 32% lemannine in TASA were entrapped within 1 h at 40°C, with an efficiency improvement of 8.87, 8.10, 7.63, and 7.78-fold than those observed in passive loading method. Transdermal experiments showed that the penetration depth and fluorescence intensity of Rhodamine B from binary ethosome prepared by pH gradient active loading method were much greater than that from binary ethosome prepared by passive loading method or hydroalcoholic solution. These results suggested transmembrane pH gradient active loading method may be an effective method to prepare alkaloids ethosomal systems at the temperatures below the Tc of PC.

  7. 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.

  8. Purification of total alkaloids from Croton tiglium L.%巴豆总生物碱的纯化工艺研究

    Institute of Scientific and Technical Information of China (English)

    肖祖平; 曾宝; 李生梅; 唐君苹; 林吉; 赖小平

    2012-01-01

    Objective To determine the technology for purification of total alkaloids from Croton tiglium L. by macroporous resin. Methods Acidic dye colorimetry was used to determine the total alkaloids. The adsorption and desorption performances of HPD400, AB-8, NKA-9, ADS-17 and D101 macroporous resins were compared and purification conditions optimized . Results D101 resin was selected because it was separated most effectively. The concentration of sample solution was 1.5 g o mL-1. The adsorption flow rate was 1.5 BV · h -1. Crude medicinal material to resin was 9:2, then 4 BV water and 4 BV 30% ethanol were used as the eluting solvent to wash the resin, collecting 30% ethanol elution. Conclusion This method is simple and feasible, which can be used to separate and purify total alkaloids from Croton tiglium L..%目的 研究大孔树脂分离纯化巴豆总生物碱的工艺.方法 采用分光光度法测定总生物碱,筛选HPD400、AB-8、NKA-9、ADS-17、D101树脂对巴豆总生物碱的吸附和解吸附能力,并优化分离纯化条件.结果 优选出D101树脂,上样液浓度为生药1.5 g ·mL-1,吸附流速1.5 BV·h-1,药材量∶树脂量=9∶2,4 BV水除杂后用4 BV 30%乙醇冲洗收集目标滤液.结论 该方法简便易行,适合于巴豆总生物碱的分离纯化.

  9. 仙鹤草总生物碱提取工艺研究%Technology for extracting total alkaloids from Herba agrimoniae

    Institute of Scientific and Technical Information of China (English)

    贤景春; 陈丹; 何雪燕

    2011-01-01

    [Objective]The optimum extraction technology was developed in order to establish practical basis for the development and utilization of Herba agrimoniae. [ Method] The total alkaloids from Herba agrimoniae were extracted by using ethanol. The effects of different ethanol concentrations, temperature, extracting time and solid-solution ratios on the extraction of total alkaloid were also observed. Furthermore, an orthogonal experiment was carried out to optimize the extraction technology. [Result]The best parameters are as follows: 80% ethanol as extractant, 1:20 solid-solution ratios, 70℃ temperature and 1.5 h extraction time. The total alkaloid in Herba agrimoniae reached 1.31 mg/g using the optimized methodology. [Conclusion]Using ethanol to extract the total alkaloids from Herba agrimoniae is simple, convenient and efficient.%[目的]确定仙鹤草总生物碱提取的最佳工艺,为仙鹤草的开发利用奠定理论基础.[方法]采用乙醇浸提法对仙鹤草总生物碱进行提取,探讨溶剂浓度、浸提温度、浸提时间和料液比对总生物碱提取的影响,并采用正交法对提取工艺进行优化.[结果]溶剂浓度对仙鹤草总生物碱提取的影响较大,其次是温度,料液比影响较小.优化后的最佳提取工艺条件为:乙醇浓度80%、浸提时间1.5 h、浸提温度70℃、料液比1:20,在此工艺条件下仙鹤草总生物碱的平均提取量为1.31 mg/g.[结论]以乙醇浸提法提取仙鹤草总生物碱简单方便,且提取率较理想.

  10. Investigations into the total synthesis of insect antifeedant clerodanes

    NARCIS (Netherlands)

    Luteijn, J.M.

    1982-01-01

    Among the still growing group of clerodane type diterpenes, those compounds possessing insect antifeedant activity have drawn much attention.Surprisingly, at the beginning of our investigations, only a few attempts towards the total synthesis of clerodanes had been made. During the last few years th

  11. Enantioselective Total Synthesis of the (+) Antipode of Zeylenone

    Institute of Scientific and Technical Information of China (English)

    An LIU; Zhan Zhu LIU; Zhong Mei ZOU; Shi Zhi CHEN; Li Zhen XU; Shi Lin YANG

    2004-01-01

    Starting from shikimic acid, the total synthesis of zeylenone was studied. The product was proved to be the (+)antipode of zeylenone through analysis and comparison of their respective spectra (including NMR, MS, IR and CD) and optical data. The absolute configuration of the natural product was thus determined to be (1 S,2S,3R).

  12. 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.

  13. 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...

  14. Total synthesis of the proposed structure of astakolactin

    Directory of Open Access Journals (Sweden)

    Takayuki Tonoi

    2014-10-01

    Full Text Available The first total synthesis of the proposed structure of astakolactin, a sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization.

  15. Total synthesis of the proposed structure of astakolactin

    Science.gov (United States)

    Mameda, Keisuke; Fujishiro, Moe; Yoshinaga, Yutaka

    2014-01-01

    Summary The first total synthesis of the proposed structure of astakolactin, a sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. PMID:25383112

  16. Vinca alkaloids.

    Science.gov (United States)

    Moudi, Maryam; Go, Rusea; Yien, Christina Yong Seok; Nazre, Mohd

    2013-11-01

    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.

  17. Optimization of Supercritical Fluid Extraction of Total Alkaloids, Peimisine, Peimine and Peiminine from the Bulb of Fritillaria thunbergii Miq, and Evaluation of Antioxidant Activities of the Extracts

    Directory of Open Access Journals (Sweden)

    Xiao Ruan

    2016-06-01

    Full Text Available Supercritical fluid extraction (SFE was used to extract total alkaloids, peimisine, peimine and peiminine from the bulb of Fritillaria thunbergii Miq. The antioxidant capacity of the extracts was evaluated by DPPH radical scavenging activity (DPPH-RSA, ABTS radical scavenging activity (ABTS-RSA and ferric reducing capacity (FRAP assay. A central composite design (CCD with four variables and five levels was employed for optimization of process parameters, and response surface plots were constructed in accordance with a second order polynomial model. Under optimal conditions of 3.0 h, 60.4 °C, 26.5 MPa and 89.3% ethanol, the highest yields were predicted to be 3.8 mg/g for total alkaloids, 0.5 mg/g for peimisine, 1.3 mg/g for peimine and 1.3 mg/g for peiminine, and the antioxidant capacity of extracts displayed EC50, DPPH value of 5.5 mg/mL, EC50, ABTS value of 0.3 mg/mL and FRAP value of 118.2 mg ascorbic acid equivalent (AAE/100 g.

  18. A Facile Synthesis of Deaza-Analogues of the Bisindole Marine Alkaloid Topsentin

    Directory of Open Access Journals (Sweden)

    Gianfranco Favi

    2013-02-01

    Full Text Available A series of substituted ethyl 1-[(tert-butoxycarbonylamino]-2-methyl-5- (1-methyl-1H-indol-3-yl-4-[(1-methyl-1H-indol-3-ylcarbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98% by one-pot reactions between β-dicarbonyl compounds 12a–e and 1,2-diaza-1,3-diene (DD 13. Derivatives 10a,c–e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel.

  19. A facile synthesis of deaza-analogues of the bisindole marine alkaloid topsentin.

    Science.gov (United States)

    Carbone, Anna; Spanò, Virginia; Parrino, Barbara; Ciancimino, Cristina; Attanasi, Orazio A; Favi, Gianfranco

    2013-02-26

    A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5- (1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a-e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c-e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel.

  20. 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.

  1. Asymmetric Total Synthesis of a Diastereisomer A of Tuxpanolide

    Institute of Scientific and Technical Information of China (English)

    WANG,Jin-Xin; ZHANG,Chao-Xin; LI,Ying

    2004-01-01

    @@ α-Alkylidene-β-hydroxy butyrolactones have been attractive and challenging targets for organic synthesis in various laboratories because that not only they are rich in skeletal diversity and stereochemistry complexity but also many of them possess quite intriguing and wide biological activities.[1] A novel class of the phytane-type diterpenoid named Tuxpanolide, bearing α-alkylidene-β-hydroxy-γ-butyrolactone skeleton, was isolated from Perymenium hintonii in Central Mexico by Maldonado and co-wokers in 1998.[2] Now we firstly report the efficient strategy of the stereocontrolled total synthesis of a diastereisomer A of Tuxpanolide.

  2. Total Synthesis of Putative 11-epi-Lyngbouilloside Aglycon

    Science.gov (United States)

    Kolleth, Amandine; Gebauer, Julian; ElMarrouni, Abdelatif; Lebeuf, Raphael; Prévost, Céline; Brohan, Eric; Arseniyadis, Stellios; Cossy, Janine

    2016-01-01

    We report here the total synthesis of 11-epi-lyngbouilloside aglycon. Our strategy features a Boeckman-type esterification followed by a RCM to form the 14-membered ring macrolactone and a late-stage side chain introduction via a Wittig olefination. Overall, the final product was obtained in 20 steps and 2% overall yield starting from commercially available 3-methyl-but-3-enol. Most importantly, the strategy employed is versatile enough to eventually allow us to complete the synthesis of the natural product and irrevocably confirm its structure. PMID:27556024

  3. Total Synthesis of Lagunamide A via Remote Vinylogous Mukaiyama Aldol Reactions, Chemical Studies Toward the Total Synthesis of Micromide and Preliminary Studies Toward the Total Synthesis of Azaspirene

    OpenAIRE

    2016-01-01

    Lagunamide A represents a class of novel cyclic depsipeptide obtained from the marine cyanobacterium Lyngbya majuscula. With an array of biological activity and impressive IC50 values including anti-malarial properties (IC50 0.19-0.91 μM), significant cytotoxic properties against P388 murine leukemia cell lines (IC50 6.4-20.5 nM) and ileocecal colon cancer (1.6 nM), lagunamide A shows promise as an extremely powerful therapeutic agent. Unexpectedly, in a recent total synthesis of lagunamide ...

  4. Effect of Potato virus X on total phenol and alkaloid contents in Datura stramonium leaves Efeito do Potato virus X no conteúdo de fenóis totais e alcalóides em folhas de Datura stramonium

    Directory of Open Access Journals (Sweden)

    Lígia Maria Lembo Duarte

    2008-02-01

    Full Text Available The present paper reports results of the effect of Potato virus X (PVX on the contents of total phenols and alkaloids in leaves of Datura stramonium. A significant decrease in the contents of phenols and alkaloids was observed in leaves inoculated with PVX (X-I. However, there was an increase in the percentage of phenols in leaves rubbed with phosphate buffer (C1-I and in leaves from the nodes immediately above, possibly induced by mechanical injury. Gas chromatography/mass spectroscopy revealed amounts of scopolamine in samples submitted to all treatments, except X-I, in which the amount of this alkaloid was low. High amounts of an unidentified compound (molecular ion m/z 302 and a prominent peak at m/z 129 were noted in extracts from leaves X-I, C1-I and leaves from the nodes immediately above the leaves inoculated with PVX. It is suggested that the synthesis and accumulation of the unidentified compound is a result of stress from mechanical injury and virus inoculation.O presente trabalho relata resultados sobre a ação do Potato virus X (PVX no conteúdo de fenóis totais e alcalóides em folhas de Datura stramonium. Uma diminuição significativa no conteúdo dessas substâncias foi observada nas folhas inoculadas com o PVX (X-I. Entretanto, houve um aumento na porcentagem de fenóis nas folhas friccionadas com tampão fosfato (C1-I e nas acima das friccionadas, possivelmente induzido por injúria mecânica. Cromatografia gasosa/espectroscopia de massas revelou quantidades de escopolamina nas amostras submetidas a todos os tratamentos, exceto em X-I, no qual a quantidade deste alcalóide foi baixa. Altas quantidades de uma substância não identificada (íon molecular m/z 302 e um proeminente pico a m/z 129 foram notadas em extratos a partir de folhas dos tratamentos X-I, C1-I e nas acima das inoculadas com o PVX. Sugere-se que a síntese e acúmulo da substância não identificada é um resultado do estresse causado pela injúria mec

  5. Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units

    Science.gov (United States)

    Wu, Yong; Xiong, De-Cai; Chen, Si-Cong; Wang, Yong-Shi; Ye, Xin-Shan

    2017-03-01

    Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

  6. Total Synthesis of Six 3,4-Unsubstituted Coumarins

    Directory of Open Access Journals (Sweden)

    Wenqing Gao

    2013-12-01

    Full Text Available In this article we describe a new methodology for the total synthesis of 3,4-unsubstituted coumarins from commercially available starting materials. Six examples were prepared, including five naturally occurring coumarins—7-hydroxy-6,8-dimethoxy-coumarin (isofraxidin, 7-hydroxy-6-methoxycoumarin (scopoletin, 6,7,8-trimethoxy-coumarin, 6,7-dimethoxycoumarin (scoparone, and 7,8-dihydroxycoumarin (daphnetin and one synthetic coumarin, 7-hydroxy-6-ethoxycoumarin. Moreover, five important o-hydroxybenzaldehyde intermediates were also obtained, namely 2,4-dihydroxy-3,5-dimethoxybenzaldehyde, 2,4-dihydroxy-5-methoxybenzaldehyde, 5-ethoxy-2,4-dihydroxy-benzaldehyde, 2-hydroxy-3,4,5-trimethoxybenzaldehyde, and 2-hydroxy-4,5-dimethoxy-benzaldehyde. The method developed herein involves just three or four steps and allows for the rapid synthesis of these important molecules in excellent yields. This is the first synthesis of 6,7,8-trimethoxycoumarin and 7-hydroxy-6-ethoxycoumarin.

  7. Synthesis of the Enantiomers of Tedanalactam and the First Total Synthesis and Configurational Assignment of (+)-Piplaroxide.

    Science.gov (United States)

    Romero-Ibañez, Julio; Xochicale-Santana, Leonardo; Quintero, Leticia; Fuentes, Lilia; Sartillo-Piscil, Fernando

    2016-04-22

    Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additionally, the (+)- and (-)-enantiomers of piplaroxide were obtained from their respective tedanalactam precursor, and the absolute configuration of the naturally occurring (+)-piplaroxide was determined. The present approach represents not only the shortest synthesis of (-)-tedanalactam but also the first total synthesis of (+)-piplaroxide, a repellent against the leafcutter ant Atta cephalotes.

  8. An unexpected reaction pathway in the synthesis of the ABCE framework of strychnine-type alkaloids - A multidisciplinary study

    Science.gov (United States)

    Šoral, Michal; Markus, Jozef; Doháňošová, Jana; Šoralová, Stanislava; Dvoranová, Dana; Chyba, Andrej; Moncol, Ján; Berkeš, Dušan; Liptaj, Tibor

    2017-01-01

    Acid-catalyzed cyclization of spirocyclic 1‧-benzyl-2‧-(prop-2-en-1-yl)spiro[indole-3,3‧-pyrrolidine]-5‧-one (1) was performed. The pentacyclic product of Povarov-like imino-Diels-Alder reaction was isolated in high yield instead of expected tetracyclic aza-Prins intermediate. The unusual exotic alkaloid-type structure of the resulting molecule 2 was unambiguously confirmed by a detailed NMR analysis using a set of 2D NMR spectra including an INADEQUATE experiment. The relative configuration of 2 was predicted from the synthesis mechanism and DFT geometry calculations and independently confirmed using NOESY and residual dipolar coupling (RDC) assisted NMR analysis in stretched crosslinked polystyrene gels. The reversibility of the cycloaddition in aprotic solvents was observed. A new reaction pathway yielding a rare 6-5-5-5 tetracyclic spiroindoline 3 was suggested. The relative configuration within the tetracyclic framework was ultimately proved using Single-crystal X-ray diffraction analysis of compound 4.

  9. Crystal structure of norcoclaurine-6-O-methyltransferase, a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids.

    Science.gov (United States)

    Robin, Adeline Y; Giustini, Cécile; Graindorge, Matthieu; Matringe, Michel; Dumas, Renaud

    2016-09-01

    Growing pharmaceutical interest in benzylisoquinoline alkaloids (BIA) coupled with their chemical complexity make metabolic engineering of microbes to create alternative platforms of production an increasingly attractive proposition. However, precise knowledge of rate-limiting enzymes and negative feedback inhibition by end-products of BIA metabolism is of paramount importance for this emerging field of synthetic biology. In this work we report the structural characterization of (S)-norcoclaurine-6-O-methyltransferase (6OMT), a key rate-limiting step enzyme involved in the synthesis of reticuline, the final intermediate to be shared between the different end-products of BIA metabolism, such as morphine, papaverine, berberine and sanguinarine. Four different crystal structures of the enzyme from Thalictrum flavum (Tf 6OMT) were solved: the apoenzyme, the complex with S-adenosyl-l-homocysteine (SAH), the complexe with SAH and the substrate and the complex with SAH and a feedback inhibitor, sanguinarine. The Tf 6OMT structural study provides a molecular understanding of its substrate specificity, active site structure and reaction mechanism. This study also clarifies the inhibition of Tf 6OMT by previously suggested feedback inhibitors. It reveals its high and time-dependent sensitivity toward sanguinarine.

  10. Effect of Total Alkaloids from Yunlian on the Anxiety of Mice%云连总生物碱对小鼠焦虑行为的影响

    Institute of Scientific and Technical Information of China (English)

    靖慧军; 李乾胜; 崔瑛; 王君明; 冯志毅; 冯静

    2015-01-01

    目的:观察云连总生物碱对小鼠焦虑行为的影响,并探讨其作用机制。方法:60只雄性 SPF 级昆明种小鼠,随机分成5组,每组12只,分别为模型组,地西泮组,云连总生物碱高剂量组、中剂量组、低剂量组。在高架十字迷宫和明暗箱装置中,观察云连总生物碱对小鼠焦虑行为的影响,然后断头取脑测定脑内γ-氨基丁酸(gamma-aminobutyric acid,GABA)、谷氨酸(glu-tamic acid,Glu)和5-羟色胺(5-hydroxytrypatmine,5-HT)的含量,并对行为学实验数据和脑内递质含量作统计分析。结果:在高架十字迷宫和明暗箱装置中,云连总生物碱中剂量组对焦虑小鼠有显著抗焦虑作用(P <0.05);小鼠脑内 GABA 含量统计结果显示,与模型组比较,地西泮组和云连总生物碱中剂量组小鼠脑内 GABA 含量显著增高(P <0.05),高剂量组和低剂量组有增高趋势,而 Glu 和5-HT 在各组中差异均无统计学意义。结论:云连总生物碱对小鼠有明显抗焦虑作用,以中剂量作用明显。其作用机制与明显升高小鼠脑内抑制性递质 GABA 的含量有关。%Objective:To observe the effect of the total alkaloids of the Yunlian on the anxiety in mice to investigate its mechanism.Meth-ods:60 male SPF Kunming mice were randomly divided into 5 groups,1 2 rats in each group,respectively as model group,Diazepam group,Yunlian total alkaloids in high dose group,middle dose group and low dose group.In the elevated plus maze and clear black box device,observed the Yunlian total alkaloids on anxiety behavior in mice and detected the brain gamma-aminobutyric acid(GABA),glut-arnic acid(Glu)and 5-hydroxytrypatmine(5-HT)content,and the behavior of the experimental data and the brain in neurotransmitters were statistically analyzed.Results:In the elevated plus maze and clear black box device,Yunlian total alkaloid middle dose group had significant anti

  11. Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.

    Science.gov (United States)

    Dewey, Ralph E; Xie, Jiahua

    2013-10-01

    Alkaloids represent an extensive group of nitrogen-containing secondary metabolites that are widely distributed throughout the plant kingdom. The pyridine alkaloids of tobacco (Nicotiana tabacum L.) have been the subject of particularly intensive investigation, driven largely due to the widespread use of tobacco products by society and the role that nicotine (16) (see Fig. 1) plays as the primary compound responsible for making the consumption of these products both pleasurable and addictive. In a typical commercial tobacco plant, nicotine (16) comprises about 90% of the total alkaloid pool, with the alkaloids nornicotine (17) (a demethylated derivative of nicotine), anatabine (15) and anabasine (5) making up most of the remainder. Advances in molecular biology have led to the characterization of the majority of the genes encoding the enzymes directly responsible the biosynthesis of nicotine (16) and nornicotine (17), while notable gaps remain within the anatabine (15) and anabasine (5) biosynthetic pathways. Several of the genes involved in the transcriptional regulation and transport of nicotine (16) have also been elucidated. Investigations of the molecular genetics of tobacco alkaloids have not only provided plant biologists with insights into the mechanisms underlying the synthesis and accumulation of this important class of plant alkaloids, they have also yielded tools and strategies for modifying the tobacco alkaloid composition in a manner that can result in changing the levels of nicotine (16) within the leaf, or reducing the levels of a potent carcinogenic tobacco-specific nitrosamine (TSNA). This review summarizes recent advances in our understanding of the molecular genetics of alkaloid biosynthesis in tobacco, and discusses the potential for applying information accrued from these studies toward efforts designed to help mitigate some of the negative health consequences associated with the use of tobacco products.

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

    Science.gov (United States)

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

    2013-07-19

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

  13. Total Synthesis of Phakellistatin 13 by Solution Method

    Institute of Scientific and Technical Information of China (English)

    Qing Feng JIANG; You Jun ZHOU; Jian Zhong YAO; Jia Guo LU; Ju ZHU; Chun Quan SHENG; Can Hui ZHENG; Bing YAO

    2006-01-01

    Phakellistatin 13 is a good antitumor lead compound isolated from halobios. It was synthesized first time by solution method in combination of stepwise coupling and segment condensation. Final deprotection and cyclization were achieved according to our designed method, which was different from the reported process. The spectral data of synthetic product is consisted with literatureal data of natural product. Total synthesis of phakellistatin 13 is a significant achievement to further study of its derivatives and developing novel antitumor drugs.

  14. Study on anti-inflammatory activity and content determination of total alkaloids in Cory dalis hendersonii%矮紫堇总生物碱的含量测定及其抗炎活性研究

    Institute of Scientific and Technical Information of China (English)

    舒花; 马学燕; 李鑫; 李蕾; 井剑歌; 岐琳

    2015-01-01

    Objective To establish a method for the determination of total alkaloids of Corydalis hendersonii and to preliminarily in‐vestigate its anti‐inflammatory activity .Methods The extraction of total alkaloids was performed by using ethanol ,and the quan‐titative determination of total alkaloids was performed by using acid dye colorimetry .Two models of mice ear edema and rat paw edema were used to observe the anti‐inflammatory activity of total alkaloids .Results The linearity was good in the range of 6‐30μg · mL -1 ,r= 0 .995 9 (n= 5) .The contents of total alkaloids were 0 .20%‐0 .25% in C . hendersonii .The total alkaloids showed obvious anti‐inflammatory activity .Conclusion This method is simple ,rapid ,sensitive and accurate with good reproduc‐ibility .It is suitable for the determination of total alkaloids in C .hendersonii and the total alkaloids demonstrated anti‐inflammato‐ry activity .%目的:建立矮紫堇中总生物碱的含量测定方法,初步研究矮紫堇总生物碱的抗炎活性。方法用乙醇提取法提取生物碱,用酸性染料比色法对总生物碱进行定量测定,用小鼠耳肿胀模型和大鼠足肿胀模型测定其抗炎活性。结果小檗碱质量浓度在6~30μg · mL -1范围内线性良好,r=0.9959(n=5),矮紫堇中总生物碱含量为0.20%~0.25%;矮紫堇总生物碱具有明显的抗炎活性。结论该方法操作简便、准确,具有良好的重复性和稳定性,适用于矮紫堇中总生物碱的含量测定;矮紫堇中生物碱具有良好的抗炎活性。

  15. 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.

  16. Total synthesis of a chlorosulpholipid cytotoxin associated with seafood poisoning.

    Science.gov (United States)

    Nilewski, Christian; Geisser, Roger W; Carreira, Erick M

    2009-01-29

    Each year, there are many cases of seafood poisoning in humans worldwide. Among the various toxins isolated that contribute to these poisonings, the chlorosulpholipids are particularly intriguing because of their structural and stereochemical complexity. The mechanism of biological activity remains unknown and, although chlorosulpholipids are associated with membranes in the organisms from which they are isolated, little is understood about their role within biological membranes. The lack of availability of the natural products has impaired more in-depth biochemical studies. So far, none of the chlorosulpholipids have been obtained from total synthesis, and efficient routes to their synthesis would be desirable for the preparation of material for pharmacological characterization and proper evaluation of the risk to human health. Despite the notable advances in the science of organic synthesis, reliable methods for stereoselective construction of polychlorinated acyclic substrates are lacking, although some preliminary investigations have appeared. Here we report the synthesis of a chlorosulpholipid cytotoxin, leading to confirmation of the proposed structure and the discovery of unanticipated reactivity of polychlorinated hydrocarbons. The concise synthetic approach should enable the preparation of material in sufficient quantities to facilitate biological studies.

  17. 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.

  18. A bio-inspired total synthesis of tetrahydrofuran lignans.

    Science.gov (United States)

    Albertson, Anna K F; Lumb, Jean-Philip

    2015-02-01

    Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio- and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol.

  19. Stereocontrolled cyclic nitrone cycloaddition strategy for the synthesis of pyrrolizidine and indolizidine alkaloids.

    Science.gov (United States)

    Brandi, Alberto; Cardona, Francesca; Cicchi, Stefano; Cordero, Franca M; Goti, Andrea

    2009-08-10

    The synthesis of polyhydroxylated indolizidines and pyrrolizidines belonging to the class of iminosugars, endowed with a vast and assorted biological activity, can be achieved in a straightforward manner by a general strategy consisting of a highly stereoselective 1,3-dipolar cycloaddition of polyhydroxylated pyrroline-N-oxides followed by simple transformations of the isoxazolidine adducts. The strategy allows the complete control of the relative and absolute stereochemistry of the numerous stereogenic centers decorating these compounds.

  20. 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.

  1. Study on Optimization of Extraction Technology for Total Alkaloids of Aconitum flavum by Orthogonal Design Method%正交试验优化铁棒锤生物碱提取工艺

    Institute of Scientific and Technical Information of China (English)

    杜弢; 陈红刚; 林丽; 魏学明

    2011-01-01

    目的:优选铁棒锤生物碱的最佳提取工艺.方法:选择溶剂、提取次数、洗涤次数为考察因素,以总生物碱的含量为考察指标,采用正交试验法优选铁棒锤生物碱的最佳提取工艺.结果:铁棒锤生物碱的最佳提取工艺为浸提次数3次,提取溶剂为乙醚-三氯甲烷(3∶1),洗涤1次.结论:优选得到的提取工艺稳定性好、得率高、简便可行.%Objective:To optimize the extraction technology for total alkaloids in the root of Aconitum flavum. Method: Dissolvent, times of extraction and washing were the test factors and the total alkaloids were the test index. The orthogonal design was used to optimize the extraction technology of total alkaloids. Result: The optimal extraction method was as follows: the ether: chloroform (3: 1 ) as dissolvent, extraction 3 times and washing once.Conclusion: The technology after optimization had a good stability, the yield of total alkaloids was high, and the method was easy to operate.

  2. Total synthesis of (-)-CP2-disorazole C1.

    Science.gov (United States)

    Hopkins, Chad D; Schmitz, John C; Chu, Edward; Wipf, Peter

    2011-08-05

    The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C(1) was accomplished in 23 steps and 1.1% overall yield. A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment of the target molecule. IC(50) determinations of (-)-CP(2)-disorazole C(1) in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not containing a conjugated diene or polyene substructure element.

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

    Science.gov (United States)

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

    2013-07-24

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

  4. Chemoselectivity: the mother of invention in total synthesis.

    Science.gov (United States)

    Shenvi, Ryan A; O'Malley, Daniel P; Baran, Phil S

    2009-04-21

    IUPAC defines chemoselectivity as "the preferential reaction of a chemical reagent with one of two or more different functional groups", a definition that describes in rather understated terms the single greatest obstacle to complex molecule synthesis. Indeed, efforts to synthesize natural products often become case studies in the art and science of chemoselective control, a skill that nature has practiced deftly for billions of years but man has yet to master. Confrontation of one or perhaps a collection of functional groups that are either promiscuously reactive or stubbornly inert has the potential to unravel an entire strategic design. One could argue that the degree to which chemists can control chemoselectivity pales in comparison to the state of the art in stereocontrol. In this Account, we hope to illustrate how the combination of necessity and tenacity leads to the invention of chemoselective chemistry for the construction of complex molecules. In our laboratory, a premium is placed upon selecting targets that would be difficult or impossible to synthesize using traditional techniques. The successful total synthesis of such molecules demands a high degree of innovation, which in turn enables the discovery of new reactivity and principles for controlling chemoselectivity. In devising an approach to a difficult target, we choose bond disconnections that primarily maximize skeletal simplification, especially when the proposed chemistry is poorly precedented or completely unknown. By choosing such a strategy--rather than adapting an approach to fit known reactions--innovation and invention become the primary goal of the total synthesis. Delivery of the target molecule in a concise and convergent manner is the natural consequence of such endeavors, and invention becomes a prerequisite for success.

  5. The alkaloid profiles of Lupinus sulphureus.

    Science.gov (United States)

    Cook, Daniel; Lee, Stephen T; Gardner, Dale R; Pfister, James A; Welch, Kevin D; Green, Benedict T; Davis, T Zane; Panter, Kip E

    2009-02-25

    Lupines are common plants on the rangelands in the western United States. Lupines contain alkaloids that can be toxic and teratogenic causing congenital birth defects (crooked calf disease). One such lupine, Lupinus sulphureus, occurs in parts of Oregon, Washington, and British Columbia. Specimens of L. sulphureus from field collections and herbaria were evaluated taxonomically and by chemical means. A total of seven distinct alkaloid profiles and the individual alkaloids associated with each profile were identified. Each alkaloid profile was unique in its geographical distribution and its potential risk to livestock. In conclusion, taxonomic classification is not sufficient to determine risk, as chemical characterization of the alkaloids must also be performed.

  6. Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba.

    Science.gov (United States)

    Ku, Wai-Foong; Tan, Shin-Jowl; Low, Yun-Yee; Komiyama, Kanki; Kam, Toh-Seok

    2011-12-01

    A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.

  7. 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....

  8. A Novel Total Synthesis of (±)Shikonin

    Institute of Scientific and Technical Information of China (English)

    De Feng XU; Xiao Juan GUO; Zhao Hui XU; Shao Shun LI

    2006-01-01

    A novel total synthesis of (±)shikonin 1 was presented. The key intermediate 6 was achieved by the formylation of 1,8:4,5-bis(methylenedioxy)naphthalene 5 with N-methylforma-nilide in good yield. It was first reported that the addition of prenyllithium to 2-formyl-1,8:4,5-bismethylenedioxy naphthalene 6 gave 2-(1-hydroxy-4-methylpentyl) 1,8:4,5-bis(methylenedioxy)naphthalene 8 in 45% yield and 2-(1-hydroxy-2,2-dimethyl-3-butenyl)-1,8:4,5-bis(methylene-dioxy)naphthalene 9 in 48% yield. After the electrooxide deprotection of 8, (±)shikonin 1 was prepared in high yield.

  9. 青风藤总生物碱聚乳酸微球的制备%Preparation of Polylactic Acid Microspheres Containing Total Alkaloids of Caulis Sinomenii

    Institute of Scientific and Technical Information of China (English)

    张雯; 张兴祥

    2011-01-01

    Polylactic acid microspheres containing total alkaloids of Caulis Sinomenii were prepared by the emulsion-solvent evaporation method. The orthogonal design was adopted to optimize the preparation process. Four factors such as emulsifier amount, stirring speed, emulsification temperature and time were investigated with the evaluation indexes of particle size and encapsulation efficiency. The results showed that the prepared microspheres were smooth and spherical with mean particle size of (21.5±1.2) μm, average encapsulation efficiency of (83.4±5.6) % and drug loading of (8.7±0.4) %. The in vitro release in pH 7.4 phosphate buffer solution at 24 h was (71.3±4.5) %.%@@ 聚乳酸(PLA)及其共聚物具有良好的生物相容性和生物降解性,在人体内无积聚,最终可完全降解为二氧化碳和水.PLA微球可用于制备生物降解型缓释或定向给药体系[1,3],具有广泛的应用前景.

  10. Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using (1)H NMR analysis.

    Science.gov (United States)

    Wu, Fang; Zheng, Hua; Yang, Zheng-Teng; Cheng, Bang; Wu, Jin-Xia; Liu, Xu-Wen; Tang, Chao-Ling; Lu, Shi-Yin; Chen, Zhao-Ni; Song, Fang-Ming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Liang, Yong-Hong; Song, Hui; Su, Zhi-Heng

    2017-03-19

    Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl4)-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance ((1)H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl4 damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl4-induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl4 chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl4-induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the

  11. Determination of Total Alkaloid in the Seed of Peganum harmala by Bromophenol Blue Colorimetry%酸性染料比色法测定骆驼蓬种子总生物碱的含量

    Institute of Scientific and Technical Information of China (English)

    赵烽; 张萌佳; 姚新生

    2000-01-01

    以溴酚蓝作为测试用酸性染料,在总生物碱与其形成稳定络合物时间范围内,利用比色法制定了骆驼蓬种子中总生物碱的含量。认为此方法快速简便、准确易行。%The content of total alkaloid in the seed of Peganum harmala L. was determined by bro-mophenol blue colorimetry. It could be considered that this is a specific, quick and simple method for thedetermination of total alkaloid in the seed of P. harmala.

  12. Method Study of Determination on Total Alkaloid Content in Different Commercial Specifications of Fritillaria Cirrhosa%不同商品规格川贝母总生物碱含量测定的方法研究

    Institute of Scientific and Technical Information of China (English)

    王纯玉; 何祖新; 吴玉良

    2013-01-01

    Objective To establish the acid staining method for the determination of total alkaloid content in Fritillaria Cirrhosa.Methods The mixed solution of trichloromethane-methanol (4 ∶ 1) was adopted to extract total alkaloids in Fritillaria Cirrhosa; the acid dye staining method was used to determine the content of total alkaloids with imperialine as the index components.Methods The content of total alkaloids in 4 specifications of samples of Fritillaria Cirrhosa all were in line with the stipulation of the Chinese Pharmacopoeia (edtion 2010,Part 1).Conclusion This method does not require the sophisticated instruments,is easy and simple to operate and can be used as the quality testing method of Fritillaria Cirrhosa.%目的 建立酸性染色法用于测定川贝母中总生物碱的含量.方法 采用三氯甲烷-甲醇(4∶1)混合溶液提取川贝母总生物碱;采用酸性染料染色法,以西贝母碱为指标成分,测定总生物碱的含量.结果 4个规格川贝母样品中总生物碱含量均符合2010年版《中国药典(一部)》的规定.结论 该方法不需要复杂仪器、操作简便,可作为川贝母的质量检测方法.

  13. Study on optimization of extraction of total alkaloids from maca(Lepidium meyenii Walp.) cultivated in Yunnan%云南栽培玛咖总生物碱提取工艺优化研究

    Institute of Scientific and Technical Information of China (English)

    姜月蒙; 鲁吉珂; 巴建明; 郝利民; 余坚勇; 于沥博

    2013-01-01

    以云南栽培玛咖干粉为原料,对其中总生物碱的提取工艺进行优化.采用热水为提取溶剂,以提取温度、提取时间和料液比为考察对象,在单因素优化的基础上设计3因素3水平正交实验,研究玛咖总生物碱的最优提取条件.结果表明,各因素对玛咖总生物碱提取得率的影响顺序依次为:提取时间>料液比>提取温度.最优提取工艺为:料液比1∶20(g∶mL),温度70℃,时间100min,在此条件下,玛咖总生物碱提取得率为1.58%.%Extraction process of total alkaloids from maca (Lepidium meyenii walp.)cultivated in Yunnan was investigated.With hot water as extraction solvent,the effect of extraction temperature,extraction time and solidliquid ratio on the yield of total alkaloids were optimized and the best extraction conditions were determined with single factor test followed by three factor-three level orthogonal experiment.The results showed that the effect of the investigated factors on the total alkaloids extraction yield was in the order as:extraction time > solid-liquid ratio >extraction temperature.The optimal extraction conditions were that solid-liquid ratio of 1 ∶ 20 (g ∶ mL),extraction temperature of 70℃ and extraction time of 100min.Under these conditions the total alkaloids extraction yield was 1.58%.

  14. Inhibition of Gardenia jasminoides and Scutellaria baicalensis on hepatotoxicity of rhynchophylline total ;alkaloids:Experimental study%栀子和黄芩拮抗钩藤总碱肝毒性的实验研究*

    Institute of Scientific and Technical Information of China (English)

    张荣梅; 张许; 郭卫; 高文学; 刘卫

    2015-01-01

    Objective To investigate the inhibition of Gardenia jasminoides and Scutellaria baicalensis on hepatic damage induced by rhynchophylline total alkaloids. Methods The 30 SD rats were divided into negative control, positive control and experiment groups randomly. Rhynchophylline total alkaloids (30 mg/kg) were administrated po for 28 days and to induce hepatic damage in the rats. Meanwhile,extraction of Gardenia jasminoides and Scutellaria baicalensis was employed to treat this damage. Results Rhynchophylline total alkaloids hindered the increasing of rats' weight,increased blood AST/ALT,and resulted in hepatic inflammatory damage. Extraction of Gardenia jasminoides and Scutellaria baicalensis decreased the ratio of AST/ALT,alleviated the damage of hepatic tissue. Conclusion Gardenia jasminoides and Scutellaria baicalensis can antagonize the hepatotoxicity of rhynchophylline total alkaloids.%目的:考察栀子和黄芩对钩藤总碱致肝损伤的拮抗作用。方法30只SD大鼠随机分为阴性对照组、阳性对照组和实验组,钩藤总碱30 mg/kg灌胃给药28 d造成肝损伤,同时浓缩栀子和黄芩水煎煮液治疗。结果钩藤总碱给药大鼠体重增长减慢,血中谷草转氨酶(AST)、谷丙转氨酶(ALT)含量升高,并且有肝细胞炎性损伤,栀子和黄芩水煎煮液可抑制钩藤总碱导致的AST、ALT升高和炎性损伤。结论栀子和黄芩的水提物能对抗钩藤总碱的肝毒性。

  15. Determination of Total Alkaloids in Ganershu by Acidic Dye Colorimetry%酸性染料比色法测定肝尔舒中总生物碱的含量

    Institute of Scientific and Technical Information of China (English)

    侯振山; 蔡铝铝; 潘金火

    2011-01-01

    Objective To establish a method for content determination of total alkaloids in ganershu by a purification progress. Methods The total alkaloids were determined by acidic dye colorimetry using synephrine as the reference. The detection wavelength was 415 nm. Results The linear range of synephrine was 117.5-352.4 μg, while the average recovery was 98.68% ( RSD= 1.60% ). Conclusion This method is simple and reliable, which can be applied for the content determination of total alkaloids in ganershu.%目的 建立肝尔舒中总生物碱含量的测定方法.方法 以辛弗林作为对照品,415 nm作为测定波长,采用酸性染料比色法测定总生物碱.结果 辛弗林在117.5 ~352.4 μg范围内线性关系良好,平均加样回收率为98.68%(RSD=1.60%).结论 该方法简便可靠,可以作为肝尔舒中总生物碱含量测定的方法.

  16. Total synthesis of discodermolide: optimization of the effective synthetic route.

    Science.gov (United States)

    de Lemos, Elsa; Porée, François-Hugues; Bourin, Arnaud; Barbion, Julien; Agouridas, Evangelos; Lannou, Marie-Isabelle; Commerçon, Alain; Betzer, Jean-François; Pancrazi, Ange; Ardisson, Janick

    2008-01-01

    An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn-anti methyl-hydroxy-methyl triads of DDM, but also for the direct construction of the terminal (Z)-diene. Of particular interest is also the installation of the C13=C14 (Z)-double bond through a highly selective dyotropic rearrangement. The preparation of the middle C8-C14 fragment in two sequential stages and its coupling to the C1-C7 moiety was a real challenge and required careful optimization. Several synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a systematic structural variation of DDM and, therefore, the elaboration and exploration of novel discodermolide structural analogues.

  17. Total synthesis of the thiopeptide antibiotic amythiamicin D.

    Science.gov (United States)

    Hughes, Rachael A; Thompson, Stewart P; Alcaraz, Lilian; Moody, Christopher J

    2005-11-09

    The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thiopeptide natural product amythiamicin D, which utilizes a biosynthesis-inspired hetero-Diels-Alder route to the pyridine core of the antibiotic as a key step. Preliminary studies using a range of serine-derived 1-ethoxy-2-azadienes established that hetero-Diels-Alder reaction with N-acetylenamines proceeded efficiently under microwave irradiation to give 2,3,6-trisubstituted pyridines. The thiazole building blocks of the antibiotic were obtained by either classical Hantzsch reactions or by dirhodium(II)-catalyzed chemoselective carbene N-H insertion followed by thionation, and were combined to give the bis-thiazole that forms the left-hand fragment of the antibiotic. The key Diels-Alder reaction of a tris-thiazolyl azadiene with benzyl 2-(1-acetylaminoethenyl)thiazole-4-carboxylate gave the core tetrathiazolyl pyridine, which was elaborated into the natural product by successive incorporation of glycine and bis-thiazole fragments followed by macrocyclization.

  18. The Securinega alkaloids.

    Science.gov (United States)

    Chirkin, Eqor; Atkatlian, William; Porée, François-Hugues

    2015-01-01

    Securinega alkaloids represent a family of plant secondary metabolites known for 50 years. Securinine (1), the most abundant and studied alkaloid of this series was isolated by Russian researchers in 1956. In the following years, French and Japanese scientists reported other Securinega compounds and extensive work was done to elucidate their intriguing structures. The homogeneity of this family relies mainly on its tetracyclic chemical backbone, which features a butenolide moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C). Interestingly, after a period of latency of 20 years, the Securinega topic reemerged as a prolific source of new natural structures and to date more than 50 compounds have been identified and characterized. The oligomeric subgroup gathering dimeric, trimeric, and tetrameric units is of particular interest. The unprecedented structure of the Securinega alkaloids was the subject of extensive synthetic efforts culminating in several efficient and elegant total syntheses. The botanical distribution of these alkaloids seems limited to the Securinega, Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a limited number of plant species have been considered for their alkaloid contents, and additional phytochemical as well as genetic studies are needed. Concerning the biosynthesis, experiments carried out with radiolabelled aminoacids allowed to identify lysine and tyrosine as the precursors of the piperidine ring A and the CD rings of securinine (1), respectively. Besides, plausible biosynthetic pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive and additional studies seem necessary to understand their mode of production. The scope of biological of activities of the Securinega alkaloids was mainly centered on the CNS

  19. Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties

    Directory of Open Access Journals (Sweden)

    Han Xiao

    2014-04-01

    Full Text Available An efficient synthesis of highly functionalized chiral β-amino ester derivatives containing benzothiophene and benzothiazole moieties is developed by a Mannich-type reaction using a cinchona alkaloid-derived thiourea catalyst. The desired products were obtained in good yields and high enantioselectivities (~86% yield, >99% ee using to the optimized reaction conditions. The synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and HREI-MS analyses. The bioassays identified that compound 5dr has excellent antifungal activity, with a 60.53% inhibition rate against F. oxysporum, higher than that of the commercial agricultural fungicide hymexazol, whose inhibition rate was 56.12%.

  20. First total synthesis and stereochemical revision of laxaphycin B and its extension to lyngbyacyclamide A.

    Science.gov (United States)

    Boyaud, France; Mahiout, Zahia; Lenoir, Christine; Tang, Shoubin; Wdzieczak-Bakala, Joanna; Witczak, Anne; Bonnard, Isabelle; Banaigs, Bernard; Ye, Tao; Inguimbert, Nicolas

    2013-08-01

    The first total synthesis of laxaphycin B was accomplished through stepwise automated Solid Phase Peptide Synthesis (SPPS), leading to the structural revision of its stereochemistry especially with regard to the configuration of one of the two 3-hydroxyleucines of this cyclic dodecapeptide of marine origin. The analogous Lyngbyacyclamide A was obtained by an extension of this synthesis.

  1. Indole alkaloids and terpenoids from Tabernaemontana markgrafiana

    DEFF Research Database (Denmark)

    Nielsen, H.B.; Hazell, A.; Hazell, R.

    1994-01-01

    The bark of Tabernaemontana markgrafiana yielded five acetylated pentacyclic triterpenes and 24 monoterpene indole alkaloids. The major triterpene was baurenyl acetate, which constituted ca 6% of the crude petrol extract. An X-ray study of iso-ursenyl acetate was carried out for the first time....... The indole alkaloids were primarily of the iboga-type and constituted ca 3% of the dried bark and 20% of the total extracts. The major alkaloids were coronaridine, (19S)-heyneanine, voacangine and ibogamine. Among the minor components, four new alkaloids were identified: 5,6-dehydro-coronaridine, 3R...

  2. Six new alkaloids from Melodinus henryi.

    Science.gov (United States)

    Ma, Ke; Wang, Jun-Song; Luo, Jun; Kong, Ling-Yi

    2015-01-01

    A total of six new alkaloids, melodinhenines A-F (1-6), were isolated from Melodinus henryi. Melodinhenines A and B are new eburnan-vindolinine-type bisindole alkaloids and melodinhenines C-F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan-vindolinine-type bisindole alkaloid using this method.

  3. LC-MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni.

    Science.gov (United States)

    Lin, Aihua; Su, Xiaochun; She, Dan; Qiu, Kuncheng; He, Qianmei; Liu, Yiming

    2016-01-01

    A rapid, specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous determination of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma. Plasma samples were pretreated via simple protein precipitation with methanol and ephedrine hydrochloride was used as internal standard. Chromatographic separation was carried out on an ZORBAX Eclipse XDB-C18 column (2.1×150mm, 3.5μm) by gradient elution with methanol and 10mM ammonium acetate (adjusted to pH 4.0 with formic acid). The quantification of the analytes was performed by mass spectrometry with TurboIonSpray ionization (ESI) inlet in the positive ion multiple reaction monitoring (MRM) mode. The results showed that the calibration curve was linear in the concentration range of 0.510∼306.3ngmL(-1) for strychnine, brucine and 0.102∼306.0ngmL(-1) for strychnine N-oxide and brucine N-oxide, respectively. The intra- and inter-day precisions were less than 14.9%, and the accuracy ranged from 89.4 to 113% at three QC levels for the 4 analytes. The validated method was successfully applied to the pharmacokinetic study of strychnine, brucine, strychnine N-oxide and brucine N-oxide in rat plasma after oral administration of each monomer and the total alkaloids from Semen Strychni. After single oral administration of the total alkaloids from Semen Strychni at 4 dose levels, Cmax, AUC0-t of strychnine and brucine increased and were proportional to the oral doses. In comparative pharmacokinetics studies, no significant difference was found between each monomer and the total strychnos alkaloids on the pharmacokinetic parameters such as Cmax and AUC. Mean Cmax and AUC of strychnine and brucine were slight increased in the monomer groups in comparison to the total strychnos alkaloids groups, which suggested that some other alkaloids in the Semen Strychni may decrease the absorption of strychnine and brucine in body.

  4. 超声提取白刺中总生物碱及大孔树脂纯化的工艺研究%Ultrasound extraction total alkaloids from Nitraria sibirica Pall and process research of macroporous resin purification

    Institute of Scientific and Technical Information of China (English)

    王玉玲; 曾会明; 张建秋; 马挺军

    2013-01-01

    为优化西伯利亚白刺种籽中总生物碱的提取工艺,采用超声波提取总碱,以硫酸阿托品为对照品,酸性染料比色法测定白刺中总生物碱的含量,探讨料液比、提取温度、时间、乙醇浓度4个因素的影响,确定最佳提取参数.从7种大孔吸附树脂中筛选出对白刺生物碱有最佳分离纯化效果的一种树脂,研究其对生物碱静态、动态吸附、解析效果.研究结果表明,当料液比为1∶20,温度60℃,时间40 min,乙醇浓度70%时,总生物碱提取率(生物碱/种籽重)最高,217.372 9 μg/g D101对白刺总生物碱的吸附、解析效果最好,对其进行动态吸附,可知最佳的工艺条件为上样液pH值为5,流速为0.75 mL/min,乙醇的洗脱浓度为80%.%In order to optimize the extract condition, total alkaloids in Nitraria sibirica was extracted by ultrasound and the content of total alkaloids was determined by the acidic dye colorimetry, the effects of solid-liquid ratio, temperature, time and ethanol concentration on the optimum extraction parameters were investigated, thereby determining the optimal extraction parameters; the best one of isolation and purification from seven kinds of resin were screened out to research its effects on the alkaloids of static, dynamic adsorption. The results show that with the conditions of solid-liquid ratio of 1:20, temperature 60 ℃, time 40 minutes, ethanol concentration of 70%, the highest total alkaloid extract rate was 217.372 9 μg/g; the adsorption and resolution effects of D101 on N. sibirica's total alkaloids were the best, the dynamic adsorption tests proved that the optimum process conditions were: sample solution pH 5, flow rate 0.75mL/min, ethanol concentration 80%.

  5. Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A

    Science.gov (United States)

    Han, Yi-Xin; Jiang, Yan-Long; Li, Yong; Yu, Hai-Xin; Tong, Bing-Qi; Niu, Zhe; Zhou, Shi-Jie; Liu, Song; Lan, Yu; Chen, Jia-Hua; Yang, Zhen

    2017-01-01

    Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A--which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids.

  6. Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A

    Science.gov (United States)

    Han, Yi-Xin; Jiang, Yan-Long; Li, Yong; Yu, Hai-Xin; Tong, Bing-Qi; Niu, Zhe; Zhou, Shi-Jie; Liu, Song; Lan, Yu; Chen, Jia-Hua; Yang, Zhen

    2017-01-01

    Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A—which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids. PMID:28139648

  7. 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.

  8. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolylpyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Directory of Open Access Journals (Sweden)

    Gerhard Kelter

    2013-03-01

    Full Text Available 2,5-bis(3′-Indolylpyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  9. Synthesis and antiproliferative activity of 2,5-bis(3'-indolyl)pyrroles, analogues of the marine alkaloid nortopsentin.

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-03-01

    2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  10. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-01-01

    2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes. PMID:23455514

  11. A Submarine Journey: The Pyrrole-Imidazole Alkaloids

    Directory of Open Access Journals (Sweden)

    Alessandra Scolaro

    2009-11-01

    Full Text Available In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity − from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products.

  12. A submarine journey: the pyrrole-imidazole alkaloids.

    Science.gov (United States)

    Forte, Barbara; Malgesini, Beatrice; Piutti, Claudia; Quartieri, Francesca; Scolaro, Alessandra; Papeo, Gianluca

    2009-11-27

    In his most celebrated tale "The Picture of Dorian Gray", Oscar Wilde stated that "those who go beneath the surface do so at their peril". This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity--from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products.

  13. A Submarine Journey: The Pyrrole-Imidazole Alkaloids

    Science.gov (United States)

    Forte, Barbara; Malgesini, Beatrice; Piutti, Claudia; Quartieri, Francesca; Scolaro, Alessandra; Papeo, Gianluca

    2009-01-01

    In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity – from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products. PMID:20098608

  14. Alkaloids from Delphinium pentagynum.

    Science.gov (United States)

    Díaz, Jesús G; Ruiz, Juan García; Herz, Werner

    2004-07-01

    Aerial parts of a collection of Delphinium pentagynum Lam. from Niebla, Southern Spain, furnished one diterpene alkaloid, 2-dehydrodeacetylheterophylloidine, two norditerpene alkaloids, 14-demethyl-14-isobutyrylanhweidelphinine and 14-demethyl-14-acetylanhweidelphinine, the known alkaloids 14-deacetylnudicauline, methyllycaconitine, 14-deacetyl-14-isobutyrylnudicauline, 14-acetylbrowniine, browniine, delcosine, lycoctonine, 18-methoxygadesine, neoline, karakoline and the aporphine alkaloid magnoflorine. Structures of the alkaloids were established by MS, 1D and 2-D NMR techniques.

  15. Alkaloid diversity in Galanthus elwesii and Galanthus nivalis.

    Science.gov (United States)

    Berkov, Strahil; Bastida, Jaume; Sidjimova, Borjana; Viladomat, Francesc; Codina, Carles

    2011-01-01

    Seventy alkaloids of galanthamine, lycorine, homolycorine, tazettine, haemanthamine, narciclasine, and tyramine types were detected by GC/MS in 25 Galanthus elwesii and seven Galanthus nivalis populations, collected from different locations in Bulgaria. Intraspecies diversity in the alkaloid profiles regarding the main alkaloid types (chemotypes) was observed. Tyramine-type protoalkaloids (namely, hordenine and its derivatives) were dominant in 19 populations of G. elwesii. In other populations of G. elwesii, the plants accumulated mainly homolycorine-, lycorine-, and galanthamine-type alkaloids. The alkaloid profiles of G. nivalis were dominated by narciclasine-, galanthamine-, lycorine-, haemanthamine-, or tazettine-type compounds. Geographical distribution of chemotypes indicated a relationship between populations, since adjacent populations often displayed similar alkaloid profiles. The results from year-to-year sampling and transplantation experiments imply genetic determination of alkaloid synthesis in the two studied species of Galanthus.

  16. 微波辅助提取牡丹雄蕊总生物碱工艺研究%The microWave-assisted extraction technology of total alkaloids from peony stamens

    Institute of Scientific and Technical Information of China (English)

    马传利; 郑国生; 周远明; 史美丽

    2014-01-01

    采用微波辅助法提取牡丹雄蕊中的总生物碱。考察了料液比、浸润时间、微波加热提取时间、微波功率、pH值和乙醇浓度等对提取率的影响。结果表明,牡丹雄蕊总生物碱的最佳提取工艺条件为:料液比1:20,浸润时间24 h,微波加热提取时间15 min,微波功率500 W,pH 值3和乙醇浓度80%。在此最佳工艺条件下,牡丹雄蕊中总生物碱提取率为2.16%。%Total alkaloids were extracted from peony stamens through microwave-assisted technique. Effects of the ratio of sample weight to solvent volume,soakage time,microwave radiation time,microwave power,pH value and ethanol concentration were studied. Result shows that the optimum technology of the total alkaloids extraction:1 : 20 of solid to liquid,24 h of soakage in solvent,15 min of microwave-assisted extraction,500 W of microwave power,3 of pH value and 80% ethanol. Under the optimized conditions, the extraction percent of total alkaloids from peony stamens is about 2. 16% .

  17. 正交试验法优化苦豆子总生物碱的超声提取工艺%Optimization of Ultrasonic Extraction Process for Total Alkaloids from Sophora Alopecuroides L.by Orthogonal Test

    Institute of Scientific and Technical Information of China (English)

    李军; 郝彩琴; 马小兰; 王海霞; 王建建; 冷晓红

    2014-01-01

    Objective To optimize ultrasonic extraction process of total alkaloids from Sophora Alopecuroides L..Method With extraction rate of total alkaloids as index,effects of liquid -solid ratio,ultrasonic temperature,ethanol concentration,ultrasonic time,extraction times on extraction process were investigated by single factor test and orthogonal test.Result The influencing order of each factors on ultrasonic extraction process of total alkaloids was ultrasonic temperature>liquid-solid ratio>extraction time>ethanol concentration.Optimum extraction process was as following:ultrasonic extracted 2 times with 16 times the amount of 65%ethanol,20 min one time,ultrasonic temperature 30℃.Conclusions This optimized process was stable and feasible with high extraction rate.%目的:优选苦豆子中总生物碱的超声提取工艺。方法:以总生物碱提取率为指标,采用单因素和正交试验考察料液比、超声温度、乙醇浓度、超声时间、提取次数对提取工艺的影响,确定最佳提取工艺。结果:各因素对超声提取工艺的影响顺序为超声温度>料液比>超声时间>乙醇浓度;最佳提取工艺为用65%乙醇,按料液比1:16,温度30℃,超声提取2次,每次20min。结论:优选的提取工艺稳定可行,提取率高。

  18. 狗牙花总生物碱的镇痛作用和精神依赖性的实验研究%Experimental study on the effects of total Ervatamia yunnansis alkaloid on analgesia and psychological dependence

    Institute of Scientific and Technical Information of China (English)

    栗志远; 王新红; 周铎; 张晓冬

    2016-01-01

    Objective To observe the effects of total Ervatamia yunnansis alkaloid on analgesia and psychological dependence in mice.Methods The hot plate test and conditional place preference test were used to valuate analgesic effect and the psychological dependence of total Ervatamia yunnansis alkaloid in mice.Results Following abdominal injection of total Ervatamia yunnansis alkaloid at dosages of 5 mg/kg and 20 mg/kg, latency of hot plate reaction of the mice was significantly prolonged(P<0.05 or <0.01).But, after medication of Ervatamia yunnansis at dosages of 5 and 20 mg/kg for 7 days, the time of staying in the drug-pair compartment wasn′t significantly extended and place preference wasn′t developed in mice.Conclusion Total Ervatamia yunnansis alkaloid seemed to have good analgesic effects and no psychological dependence was observed.%目的 观察狗牙花总生物碱(Ervatamia yunnansis)的镇痛作用和精神依赖性.方法 选择昆明种雌性小鼠72只,其中小鼠热板法实验32只,条件性位置偏爱试验40只,按数字表法随机分为生理盐水对照组、吗啡组、狗牙花总生物碱低剂量组(5 mg/kg)及高剂量组(20 mg/kg)组.分别采用小鼠热板法和条件性位置偏爱试验观察狗牙花总生物碱镇痛作用和精神依赖性.结果 腹腔注射5、20 mg/kg狗牙花总生物碱后小鼠热板反应潜伏期显著延长(P<0.05或<0.01);狗牙花总生物碱5、20 mg/kg连续给药7 d后,小鼠在伴药侧逗留时间均无明显延长,没有形成条件性位置偏爱.结论 狗牙花总生物碱具有镇痛作用且无精神依赖性.

  19. 星点设计-响应面法优化川芎生物碱提取工艺%Optimization of extraction technology for total alkaloids from Ligusticum chuanxiong by central composite design/response surface methodology

    Institute of Scientific and Technical Information of China (English)

    马丽娜; 白曼; 王景媛; 史亚军; 王昌利

    2013-01-01

    目的 优选川芎总生物碱的提取工艺.方法 对川芎采用乙醇回流提取的方法,进行星点设计,以乙醇浓度、醇倍数、提取时间为自变量,以川芎中总生物碱含量为因变量,通过对自变量各水平的多元线性回归及二项式拟合,用响应面法优选出最佳提取工艺,同时进行预测分析.结果 确定了最佳提取工艺为用8倍90%的乙醇提取2次,每次2h,提取的川芎总生物碱含量为0.693 mg·g-1,二项式拟合复相关系数R2=0.957 3.结论 星点设计-响应面法优选川芎中总生物碱的提取工艺,方法简单,精密度高,可预测性好.%Objective To optimize the extraction process of total alkaloids from Ligusticum chuanxiong. Methods Independent variables were ethanol concentration, reflux time and solvent fold, and dependent variable was extraction rate of total alkaloids from Ligusticum chuanxiong. Levels of independent variables were regressed by multiple linearity and fitted by binomial. Response surface methodology was used to optimize the extraction process. We compared both observed and predicted values. Results Optimal extraction technology was: extracting twice by 8 times of 90% ethanol for 2 h each time. The optimum extraction process of total alkaloid content in Ligusticum chuanxiong was under 0.693 mg · g-1. Regression coefficients of binomial fitting complex model was as high as 0.957 3. Conclusion This extraction process of total alkaloids from Ligusticum chuanxiong by central composite design/response surface methodology is simple with high precision and good predictability.

  20. Progress in total synthesis of chimonanthine%天然产物Chimonanthine的全合成研究进展

    Institute of Scientific and Technical Information of China (English)

    邢瑞光; 李亚男

    2012-01-01

    在吲哚生物碱大家族中,其中有一类化合物是以色氨的二聚、三聚甚至多聚的形式存在于自然界中,它们就是吸引有机化学家们广泛研究兴趣的环色胺类生物碱.Chimonanthine则是这个大家族中最简单最重要的一类化合物.根据其旋光性的不同,Chimonanthine有meso-Chimonanthine、(+)-Chimonanthine和(-)-Chimonanthine 3种类型.由于Chimonanthine在环色胺类吲哚生物碱中有着特殊的地位,所以早在20世纪60年代Woodward等就推测,该化合物在生物体内的合成主要是通过自由基偶联发生两分子的聚合.从推测Chimonanthine的生物合成途径开始,综述了近些年来Chimonanthine的全合成研究进展,并对各类合成途径的反应条件、反应选择性、产率以及机理的研究进行了讨论和总结.%The dimmers,trimers,and higher-order oligomers of tryptamine are the most abundant indoline alkaloids in nature. These compounds that fascinating family of natural products is complex cyclotryptamine alkaloids. In which one is chimonanthine, although a simple structure, occupies an important position. According to the optical activity, chimonanthine includes three compounds; meso-chimonanthine, ( + ) -chimonanthine and ( - ) -chimonanthine. Due to the importance of chimonanthine,in the early of 1960 s,Woodward and coworkers supposed that there is a radical coupling reaction in the living organism. Beginning with a suppose of biological pathways, recent development of the total synthesis of chimonanthine is reviewed, reaction conditions, selectivity, yields and mechanisms are discussed and summarized.

  1. Synthesis of Peramine, an Anti-insect Defensive Alkaloid Produced by Endophytic Fungi of Cool Season Grasses.

    Science.gov (United States)

    Nelli, Matthew R; Scheerer, Jonathan R

    2016-04-22

    A seven-step synthesis of peramine, which required three chromatographic separations, is described. Key to the synthesis is an enolate alkylation of a pyrrole-fused diketopiperazine, reduction of the acyl pyrrole, and dehydration of the intermediate pyrrolyl carbinol to establish the pyrrolopyrazine core of peramine.

  2. Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A

    DEFF Research Database (Denmark)

    Nielsen, Daniel S; Hoang, Huy N; Lohman, Rink-Jan;

    2012-01-01

    The first total synthesis and three-dimensional solution structure are reported for sanguinamide A, a thiazole-containing cyclic peptide from the sea slug H. sanguineus. Solution phase fragment synthesis, solid phase fragment assembly, and solution macrocyclization were combined to give (1) in 10...

  3. 酸性染料比色法测定红茂草中总生物碱含量%Determination of total alkaloid in Dicranostigma leptodum(Maxim.) Fedde by acid dye colorimetry

    Institute of Scientific and Technical Information of China (English)

    赵强; 王廷璞; 董晓宁; 白斌峰; 赵海福

    2011-01-01

    The content of total alkaloid in Dicranostigma leptodum(Maxim.) Fedde(DLF) was determined by acid dye colorimetry.Using the isocorydine as standard,acid dye colorimetry conditions were as follows: pH=4.0,wavelength of 425 nm,bromocresol green liquid 1.5 mL.The standard curve was then obtained: y=0.032 x-0.033,R2=0.977 0.The concentration of alkaloid showed good linearity with its absorbability within the range of 21.6-54.0 mg/mL.The content of total alkaloid from DLF was 1.386%.The method is simple,highly sensitive and reproducible.%采用酸性染料比色法测定红茂草中总生物碱含量。以异紫定堇碱为标准品,酸性染料比色法的显色条件为:pH值4.0、波长415 nm、溴甲酚绿1.5 mL,得到标准曲线:y=0.032 x-0.033,R2=0.977 0,生物碱检测浓度在21.6-54.0 mg/mL范围内与吸收度线性关系良好,红茂草中总生物碱含量为1.386%。该方法灵敏度高、准确度好、重现性好。

  4. 荷叶总生物碱脂质体的制备及质量评价%Preparing the Liposomes of Total Alkaloids of Lotus Leaf and Carrying on the Quality Appraisal

    Institute of Scientific and Technical Information of China (English)

    赵骏; 陈弼谦

    2009-01-01

    Objective :To prepare the Liposomes of tots], alkaloids of lotus leaf, and carry on the quality appraisal. Meth-ods:Reverse phase evaporation was adopted to prepare the Leptosomes of total alkaloids of lotus leaf, the Lipesomes was separated by the cation exchange resin,and the absorbance was measured at 164nm,and the encapsulation efficiency was calculated, the impact of oil - water radio, Lecithin and the addition of drug towards encapsulation efficiency was inspec-ted. Results :The experiment indicats ,while the oil-water radio is 4:1 ,the quantity of soybean lecithin is 250mg, Liposomes is roughly spherical or elliptic, and the encapsulation efficiency is 84. 9%. Conclusion:The encapsulation efficiency of Pre-paring the Liposomes of total alkaloids of lotus leaf by this method is higher.%目的:制备荷叶总生物碱脂质体,并进行质量评价.方法:采用逆相蒸发法制备荷叶总生物碱,以阳离子交换树脂法分离脂质体,于164nm处测定吸光度,计算包封率;考察油水比、卵磷脂及药物的加入量对包封率的影响.结果:实验表明,油水比为4:1,卵磷脂量为250mg时,所得脂质体呈球型或椭圆型,包封率为84.9%.结论:本法制备荷叶总生物碱脂质体包封率较高.

  5. 鱼腥草总生物碱的大孔吸附树脂纯化工艺%Purification Process of Total Alkaloids from Houttuynia cordata by Macroporous Resin

    Institute of Scientific and Technical Information of China (English)

    孟江; 梁慧超; 陈磊; 卢国勇; 巫丹凤

    2012-01-01

    Objective: To optimize separation and purification technology of total alkaloids from Houttuynia cordata by macroporous resin. Method: With the content of berberine hydrochloride, pepper lactam and aristololactam B as indexes, separation and purification capacity of total alkaloids from H. Cordata was compared with different types of macroporous resin and different technology conditions. Result; HPD-100 macroporous resin had the best separation and purification capacity for total alkaloids in following technology conditions; sample concentration was 20 g ? L-1 with Ph 3, flow rate was 0. 5 Ml ? Min -1, eluting reagent was ethanol solution of ammonia ( ammonia concentration 0. 5 mol ? L-1, the volume fraction of ethanol 80% ) with the amount of 4 BV, eluting velocity was 3.0 Ml ? Min-1. Conclution: HPD-100 macroporous resin could be applied to purify alkaloids from H. Cordata.%目的:优选鱼腥草总生物碱大孔吸附树脂的分离纯化工艺.方法:以盐酸小檗碱、胡椒内酰胺及马兜铃内酰胺B含量为指标,比较不同型号树脂和不同工艺条件对鱼腥草总生物碱的分离纯化能力.结果:HPD-100型大孔树脂对鱼腥草总生物碱有良好的吸附分离性能,最佳工艺条件为药液质量浓度20 g?L-1,pH 3,吸附流速0.5 mL? min -1,洗脱溶剂为氨水乙醇溶液(氨水浓度0.5 mol?L-1,乙醇体积分数80%),洗脱剂用量4 BV,洗脱速度3.0mL?min -1.结论:HPD-100型大孔树脂可用于鱼腥草总生物碱的提取纯化.

  6. 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

  7. 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)

  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. Remarkable Stereoelectronic Effect of the Methylenedioxy Phenyl System in the Total Synthesis of Cephalotaxine

    Institute of Scientific and Technical Information of China (English)

    Hua YANG; Yong Qiang WANG; Wei DongZ. LI

    2005-01-01

    Methylenedioxyphenyl unit displays a significant stereoelectronic effect in some key transformations in the total synthesis of cephalotaxine. The ring-strain of methylenedioxy ring may account for some important facile ring-skeleton rearrangements.

  10. 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

    Summary Obesity and disorder of lipid metabolism , also called dyslipidemia , have been one of the most important diseases threating people health worldwide , and is closely connected with hypertension , high serum glucose and other cardiac‐cerebral vascular diseases . The high fat diet is the main pathogenic cause of obesity and dyslipidemia , how to regulate blood lipid and control body mass effectively has been hotspots on nutriology research nowadays . Agents from natural products that inhibit fat digestion and absorption are of theoretical benefit in the treatment of obesity and dyslipidemia . Among them , lotus ( Nelumbo nuci f era) leaf is a kind of natural plant material used both in food and medicine , which contains multiple useful 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

  11. The use of ultrasound to extract total alkaloids from leonurus%利用超声法从益母草中提取总生物碱的研究

    Institute of Scientific and Technical Information of China (English)

    付君叶; 宋秋华

    2012-01-01

    利用超声波法从益母草中提取总生物碱,并利用正交试验法,分别对浸泡时间、溶剂用量、超声提取时间等因素进行了正交试验设计.正交试验因素分析结果表明:对益母草中总生物碱提取因素重要次序为:浸泡时间>溶剂用量>超声萃取时间.并得到优选后的最佳工艺条件:益母草的浸泡时间为8h,加入95%乙醇溶剂为36 g,超声波萃取时间为60 min.%Ultrasonic methods were used to extract total alkaloids from leonurus, and the immersion time, solvent amount, ultrasonic extraction time and other factors were designed by orthogonal experiments respectively. Orthogonal experimental factor analysis results showed the priority sequence of extraction factors of the total alkaloid from leonurus is: soaking time>solvent amount>ultrasonic extraction time. And the optimum conditions after optimization is: leonurus soaking hour of 8 h, 95 % ethanol solvent adding amount of 36 g, ultrasonic extraction time of 60 min.

  12. In search of a cytostatic agent derived from the alkaloid lycorine: synthesis and growth inhibitory properties of lycorine derivatives.

    Science.gov (United States)

    Evdokimov, Nikolai M; Lamoral-Theys, Delphine; Mathieu, Véronique; Andolfi, Anna; Frolova, Liliya V; Pelly, Stephen C; van Otterlo, Willem A L; Magedov, Igor V; Kiss, Robert; Evidente, Antonio; Kornienko, Alexander

    2011-12-01

    As a continuation of our studies aimed at the development of a new cytostatic agent derived from an Amaryllidaceae alkaloid lycorine, we synthesized 32 analogues of this natural product. This set of synthetic analogues included compounds incorporating selective derivatization of the C1 versus C2 hydroxyl groups, aromatized ring C, lactamized N6 nitrogen, dihydroxylated C3-C3a olefin functionality, transposed olefin from C3-C3a to C2-C3 or C3a-C4, and C1 long-chain fatty esters. All synthesized compounds were evaluated for antiproliferative activities in vitro in a panel of tumor cell lines including those exhibiting resistance to proapoptotic stimuli and representing solid cancers associated with dismal prognoses, such as melanoma, glioblastoma, and non-small-cell lung cancer. Most active analogues were not discriminatory between cancer cells displaying resistance or sensitivity to apoptosis, indicating that these compounds are thus able to overcome the intrinsic resistance of cancer cells to pro-apoptotic stimuli. 1,2-Di-O-allyllycorine was identified as a lycorine analogue, which is 100 times more potent against a U373 human glioblastoma model than the parent natural product. Furthermore, a number of synthetic analogues were identified as promising for the forthcoming in vivo studies.

  13. Insecticidal Constituents and Activity of Alkaloids from Cynanchum mongolicum.

    Science.gov (United States)

    Ge, Yang; Liu, Pingping; Yang, Rui; Zhang, Liu; Chen, Hongxing; Camara, Ibrahima; Liu, Yiqing; Shi, Wangpeng

    2015-09-21

    Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they were less active against Spodoptera litura than total alkaloids. The contact toxicity from these alkaloids against the aphid Lipaphis erysimi was significant, as the 24 h-LC50 values of alkaloids I, II, III and total alkaloids were 292.48, 367.21, 487.791 and 163.52 mg/L, respectively. The development disruption of S. litura larvae was tested, the pupation and emergence rates of S. litura decreased and the acute mortality of S. litura increased significantly by day 3 after being injected in their body cavity with 10-40 mg/L of total alkaloid. The ecdysone titer of treated S. litura larvae and prepupae declined with increasing alkaloid concentration. The alkaloids of Cynanchum mongolicum are potential insect growth inhibitors.

  14. Exploiting plant alkaloids.

    Science.gov (United States)

    Schläger, Sabrina; Dräger, Birgit

    2016-02-01

    Alkaloid-containing plants have been used for medicine since ancient times. Modern pharmaceuticals still rely on alkaloid extraction from plants, some of which grow slowly, are difficult to cultivate and produce low alkaloid yields. Microbial cells as alternative alkaloid production systems are emerging. Before industrial application of genetically engineered bacteria and yeasts, several steps have to be taken. Original alkaloid-forming enzymes have to be elucidated from plants. Their activity in the heterologous host cells, however, may be low. The exchange of individual plant enzymes for alternative catalysts with better performance and optimal fermentation parameters appear promising. The overall aim is enhancement and stabilization of alkaloid yields from microbes in order to replace the tedious extraction of low alkaloid concentrations from intact plants.

  15. Totally Ecofriendly Synthesis of Silver Nanoparticles from Aqueous Dissolutions of Polysaccharides

    OpenAIRE

    2013-01-01

    In this contribution, a totally ecofriendly synthesis of silver nanoparticles from aqueous dissolution of polysaccharides is reported. The synthesis of nanoparticles was performed using aqueous dissolutions of silver nitrate (AgNO3) and carboxymethyl-cellulose (CMC) as both reducing and stabilization agent and using different AgNO3 : CMC weight ratios. Resultant yellowish to reddish dispersions were characterized by means of transmission electron microscopy and their related techniques, such ...

  16. Total synthesis of microcin B17 via a fragment condensation approach.

    Science.gov (United States)

    Thompson, Robert E; Jolliffe, Katrina A; Payne, Richard J

    2011-02-18

    The total synthesis of the 43 amino acid antibacterial peptide Microcin B17 (MccB17) is described. The natural product was synthesized via a convergent approach from a heterocycle-derived peptide and peptide thioester fragments prepared via Fmoc-strategy solid phase peptide synthesis (SPPS). Final assembly was achieved in an efficient manner using two Ag(I)-assisted peptide ligation reactions to afford MccB17 in excellent overall yield.

  17. 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)

  18. 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

  19. Determination of total alkaloids in Croton tiglium by acid dye colorimetry%酸性染料比色法测定巴豆中总生物碱的含量

    Institute of Scientific and Technical Information of China (English)

    曾宝; 李生梅; 古俊辉; 唐君苹; 林吉; 赖小平

    2012-01-01

    目的 建立巴豆中总生物碱含量的测定方法,对不同产地的巴豆总生物碱质量分数进行比较研究.方法 以木兰花碱作为对照品,采用酸性染料比色法测定巴豆中总生物碱质量分数.结果酸性染料法的显色条件为加pH 6.0缓冲液至8 mL,加溴麝香草酚蓝3.5 mL,振摇3min,静置40 min,三氯甲烷8mL萃取,测定波长为420 nm,在0.024 6~0.147 3 mg范围内线性关系良好(r=0.999 5),平均回收率99.0%,RSD为2.75%.结论 本含量测定方法操作简单,灵敏度高,准确性、重复性好,可用于巴豆中总生物碱的含量测定.%Objective To establish a method for the assay of the total alkaloids in Croton tiglium, and investigate the contents from different origins. Methods Acidic dye colorimetry was used for the determination of total alkaloids in Croton tiglium with magnoflorine as reference substance. Results Acid dye colorimetric conditions were as follows; pH6.0 buffer to 8.0 mL, adding 3. 5 mL bromothymol blue, extracting with 8 mL chloroform, shaking out for 3 minutes, stewing for at least 40 min, then determining at the wavelength of 420 nm. The concentration of magnoflorine showed good linearity within the range of 0. 024 6-0. 147 3 mg, r = 0. 999 5, and the average recovery ratio was 99. 0% with RSD of 2. 75%. Conclusion This method is simple, highly sensitive, accurate and reproducible, which can be used for determination of the total alkaloids in Croton tiglium.

  20. A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro.

    Science.gov (United States)

    Wesche, D L; Black, J

    1990-06-01

    The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, (-)cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with (-)stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition.

  1. Solid phase total synthesis of the 3-amino-6-hydroxy-2-piperidone (Ahp) cyclodepsipeptide and protease inhibitor Symplocamide A.

    Science.gov (United States)

    Stolze, Sara C; Meltzer, Michael; Ehrmann, Michael; Kaiser, Markus

    2010-12-14

    The solid phase total synthesis of the marine cyanobacterial Ahp-cyclodepsipeptide Symplocamide A is reported as a model for a general route for the synthesis of tailor-made non-covalent serine protease inhibitors.

  2. Historical view on ergot alkaloids.

    Science.gov (United States)

    Hofmann, A

    1978-01-01

    A short survey of the history of ergot, of the original and, for a long time, only source of ergot alkaloids, is given. Once a dreaded poison, ergot has changed its role over the centuries to become a rich treasure house of valuable pharmaceuticals. In the Middle Ages it was the cause of epidemics of ergotism, which cost tens of thousands of people their lives. Ergot was first mentioned by the German physician Lonitzer in 1582 as a remedy used by midwives for quickening childbirth. The isolation of pharmacologically useful alkaloids started in 1906 with the discovery of ergotoxine and its adrenolytic activity by Barger, Carr and Dale. In 1918, Stoll isolated ergotamine, the first chemically pure ergot alkaloid, which found widespread therapeutic use in obstetrics and internal medicine. In 1935 the specific oxytocic principle of ergot, ergonovine, was discovered simultaneously in four separate laboratories. Since then, worldwide investigations on ergot alkaloids resulted in the elucidation of their structures and total syntheses and preparation of valuable therapeutics such as Methergine, Hydergine, Dihydergot, and others.

  3. 半夏生物总碱和钩藤生物总碱抗小鼠、大鼠惊厥的协同作用%Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

    Institute of Scientific and Technical Information of China (English)

    成银霞; 王明正; 陈靖京; 杨蓉; 何欣嘏; 马永刚; 杨李华; 张明升

    2007-01-01

    目的 研究半夏生物总碱(PTA)和钩藤生物总碱(UTA)抗惊厥的协同作用,并探讨其相互作用机制.方法 采用小鼠最大电休克惊厥试验和急性毒性试验检测PTA和UTA单用和三种比例(1:1,1:4,4:1)配伍的抗惊厥作用及毒性效应,并采用bliss's法分别计算它们的ED50和LD50.用等效线法评价其协同作用并计算各组配伍的受益指数(BD.制备大鼠运动皮层定位注射青霉素惊厥模型,同时采用高效液相色谱法(HPLC)测定海马区癫痫相关递质Glu、Asp、Gly、GABA的含量.结果 半夏、钩藤生物总碱4:1配伍的抗惊厥作用呈现协同,而毒性呈现相互拮抗,是PTA和UTA合用的最佳比例.而两药1:4和1:1比例配伍尽管在最大电休克惊厥试验中抗惊厥作用呈现协同,但是在毒性试验中毒性效应却呈现相加.PTA和UTA单用和4:1合用,均可明显减少海马Glu的水平,增加GABA的水平,且4:1合用组的GABA水平要比两单药组高.但对Asp、Gly无明显影响.结论 PTA和UTA以4:1合用时抗癫痫效应协同、毒性拮抗.两药合用的抗惊厥作用机制可能与其同时降低Glu能神经的兴奋性,并协同提高GABA能神经功能有关.%Aim To investigate the synergistic effect of the combination of pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA), and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1:4,1:1, 4:1, were evaluated in maximal electroshock (MES)-induced seizures and acute toxicity test in mice. Respective ED50 and LD5o were calculated with Bliss's method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices (BI) for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high

  4. Experimental Study on Total Alkaloid of Stephania delavayi Diels for Treating Rat Chronic Atrophic Gastritis%金不换总生物碱治疗大鼠慢性萎缩性胃炎的实验研究

    Institute of Scientific and Technical Information of China (English)

    吴丽萌; 赖东梅; 陈娟; 周长华; 马仁强; 陈健文

    2011-01-01

    Objective To study the effects of total alkaloid of stephania delavayi diels on treating chronic atrophic gastritis(CAG) in rats.Methods 20 mmol/L sodium deoxycholate combined 30%, 60% alcohols were given to rats for 13 weeks to establish CAG model.The rats were randomly divided into six groups: normal control group, model control group, high, medium and low doses groups with total alkaloid of stephania delavayi diels, and Sanjiu Weitain group.The acidity of gastric juice, pepsase activities and volume of blood flow in gastric mucosa were detected, and the pathologic changes of the gastric mucosa were observed by microscope.Results In total alkaloid of stephania delavayi diels treated groups, the body weight was increased( P > 0.05) and the concentration of free acid was significantly increased, while pepsase activities and volume of blood flow in gastric mucosa were obviously higher than those in the control groups (P <0.05 or P <0.01 ).Chronic infiltration of inflammatory cells and atrophy of glands on gastric mucosa were observed less in JB groups than in model group( P <0.05 or P <0.01 ).Conclusion The total alkaloid of stephania delavayi diels has the satisfactory curative efficacy for chronic atrophic gastritis in rats, which provides the pharmacological basis for its clinical application.%目的 研究金不换总生物碱对慢性胃炎的作用.方法 饮用及灌胃给予20mmol/L去氧胆酸钠、30%及60%乙醇13周建立慢性萎缩性胃炎模型后,将大鼠随机分为正常对照组,模型对照组,金不换总生物碱高、中、低剂量组和三九胃泰组.观察其对胃酸酸度、胃蛋白酶活性、胃黏膜血流量和胃黏膜组织病理的影响.结果 与模型对照组比较,金不换总生物碱可改善慢性萎缩性胃炎大鼠体重,明显增加胃液游离酸浓度、胃蛋白酶活性和胃黏膜血流量(P<0.05或P<0.01),并能明显减轻胃黏膜的病理学损害.结论 金不换生物碱对慢性萎缩性

  5. 马钱子总生物碱的定量分析及其HPLC指纹图谱%HPLC Fingerprint and Quantitative Analysis of Total Alkaloids from Strychnos nux-vomica

    Institute of Scientific and Technical Information of China (English)

    屈艳格; 陈军; 蔡宝昌

    2012-01-01

    Objective: To establish fingerprint of purified total alkaloids from processed Strychnos nux-vomica by HPLC-DAD, and provide a new method for quality control of S. nux-vomica. Method: The contents of brucine, strychnine and brucine N-oxide from purified total alkaloids of S. nux-vomica were determined by HPLC, and fingerprint was investigated. Analytical conditions of content determination were: Superstar C18 chromatographic column (4.6 mm × 250 mm, 5 μm), mobile phase of acetonitrile (A) -0.01 mol · L-1 1-heptane sulfonate and 0. 02 mol·L-1 potassium dihydrogen phosphate mixed with equal amount (adjusted pH to 2. 8 with 10% phosphonic acid) (24:76) , analysis time 20 min, column tempreture 30 ℃ , detection wavelength at 264 nm; Analysis conditions of fingerprints were on Superstar C18chromatographic column (4. 6 mm ×250 mm, 5 μm) , acetonitrile (A) - [ water-acetic acid-triethylamine (100:0. 2: 0. 2) ] (B) as mobile phase with a method of gradient elution (0-21 min, 10%-16% A; 21-55 min, 16%-40% A; 55-65 min, 10% A), parsing time 65 min, column tempreture 30℃, UV detection wavelength at 254 nm. Result: Parameters of content determination and fingerprint analysis of total alkaloids from 5. nux-vomica were in line with requirements of 2010 edition 'Chinese Pharmacopoeia' ; Content analysis of 10 batches of purified total alkaloids samples from S. nux-vomica showed that mass fraction of brucine, strychnine and brucine N-oxide were 32. 3%-37. 5% , 15.0%-18. 4% and 0. 19% -0. 23% , respectively; Fingerprint analysis of each batch of samples showed 10 common peaks and fingerprint similarity were all above 97.0%. Conclusion: Combination of content determination and fingerprint could well reflect the overall quality of total alkaloids from S. nux-vomica, preparation process of depurated total alkaloids from processed S. nux-vomica was stable, reproducible, reliable, so it was an effective quality analysis and evaluation method.%目的:建立纯化马钱子总

  6. 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

  7. 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.

  8. 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...

  9. Thin-layer chromatography of total alkaloids in Croton tiglium%巴豆生物碱的薄层色谱鉴别研究

    Institute of Scientific and Technical Information of China (English)

    李晓伟; 易智彪; 曾宝; 李生梅; 唐君苹; 袁捷

    2013-01-01

    Objective:To establish a thin layer chromatographic(TLC) method for the Croton alkaloids,and to offer evidence for quality evaluation of Fructus Crotonis. Methods: The determination was done by using TLC. With isoguanosine and magnoflorine as reference, water (6∶4∶1,5 drops of ammonia) as the develop system was established. After launching and took out air driesand developed with iodine vapor. Results: A same color spots in the TLC graph of sample existed at the corresponding positions compared with the controls. Conclusions: The established method is simple and accurate,and have a good repeatability,which will supply evidence for the quality evaluation of medicinal material of Fructus Crotonis.%  目的:建立巴豆生物碱的薄层鉴别方法,为巴豆药材的质量评价提供依据。方法:采用 TLC 法,以巴豆苷和木兰花碱为对照品,以氯仿-甲醇-水(6∶4∶1,加5滴氨水)为展开系统,碘熏显色。结果:在日光下检视,在两组对照品相应位置上,显出相同颜色的斑点。结论:该方法简便、准确、重现性好,为评价巴豆药材定性鉴别及内在质量提供了科学依据。

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

    NARCIS (Netherlands)

    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

  11. Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B.

    Science.gov (United States)

    Tello-Aburto, Rodolfo; Hallada, Liam P; Niroula, Doleshwar; Rogelj, Snezna

    2015-10-28

    The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15 were found to be about 100 times more potent, and to selectively kill MCF-7 cancerous cells.

  12. Total synthesis of exiguamines A and B inspired by catecholamine chemistry.

    Science.gov (United States)

    Sofiyev, Vladimir; Lumb, Jean-Philip; Volgraf, Matthew; Trauner, Dirk

    2012-04-16

    The evolution of a total synthesis of the exiguamines, two structurally unusual natural products that are highly active inhibitors of indolamine-2,3-dioxygenase (IDO), is described. The ultimately successful strategy involves advanced cross-coupling methodology and features a potentially biosynthetic tautomerization/electrocyclization cascade reaction that forms two heterocycles and installs a quaternary ammonium ion in a single synthetic operation.

  13. Total synthesis and absolute configuration of avenolide, extracellular factor in Streptomyces avermitilis.

    Science.gov (United States)

    Uchida, Miho; Takamatsu, Satoshi; Arima, Shiho; Miyamoto, Kiyoko T; Kitani, Shigeru; Nihira, Takuya; Ikeda, Haruo; Nagamitsu, Tohru

    2011-12-01

    The first total synthesis of extracellular factor, "Avenolide", in Streptomyces avermitilis has been achieved using a convergent approach. The stereogenic centers in two key segments were installed using Sharpless epoxidation and dihydroxylation. This synthetic study allowed the determination of the absolute configuration of avenolide as 4S,10R, and yielded important information on its structure-activity relationship.

  14. 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.

  15. 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.

  16. Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies.

    Science.gov (United States)

    Novaes, Luiz F T; Sarotti, Ariel M; Pilli, Ronaldo A

    2015-12-18

    A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.

  17. Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

    Science.gov (United States)

    Seidl, Frederick J

    2016-01-01

    Summary The scope of a recently reported method for the catalytic enantioselective bromochlorination of allylic alcohols is expanded to include a specific homoallylic alcohol. Critical factors for optimization of this reaction are highlighted. The utility of the product bromochloride is demonstrated by the first total synthesis of an antibacterial polyhalogenated monoterpene, (−)-anverene. PMID:27559385

  18. Study on Extraction Technology of Total Alkaloids from Cortex Pheilodendri by Comprehensive Weighted of Multi-index%多指标综合加权评分研究川黄柏总生物碱提取工艺

    Institute of Scientific and Technical Information of China (English)

    程弘夏; 周军伟; 王仲; 李其兰

    2011-01-01

    目的:优选渗漉法对黄柏总生物碱提取的最佳工艺.方法:采用L9(34)正交设计法对黄柏药材提取时所用乙醇浓度、乙醇用量、渗漉速度、药材粒度进行考察,通过多指标综合加权评分优选黄柏的提取工艺.结果:黄柏总生物碱提取的最佳工艺:乙醇浓度65%,乙醇用量为生药的12倍,渗漉速度为1ml·min-1,药材粒度为10 ~20目.结论:经正交试验优选的工艺可操作性强,工艺稳定,成本低,对环境无污染,安全可靠,适合于工业生产.%Objective: To determine the optimal extraction process for total alkaloids from cortex phellodendri by percolation. Method; L9(34) Orthogonal design was used in studying the effect of alcohol concentration and volume,percolation rate and medicinal material size on the content of alkaloid. Result: The optimum extraction process was the follows; 12 times of 65% alcohol,percolation rate of 1 ml/min,medicinal material size of 10-20 mesh. Conclusion; This extraction process is stable and feasible with low cost,no environmental pollution, high safety and reliability which is suitable for the industrial production.

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

    Science.gov (United States)

    Arefolov, Alexander; Panek, James S

    2005-04-20

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

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

    Science.gov (United States)

    Calter, Michael A; Liao, Wensheng

    2002-11-06

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

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

    Science.gov (United States)

    Fuwa, Haruhiko

    2016-01-01

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

  2. Alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Yu, Bing-Wu; Chen, Jian-Yong; Wang, Yan-Ping; Cheng, Kin-Fin; Li, Xiao-Yu; Qin, Guo-Wei

    2002-10-01

    The alkaloids, dechloroacutumidine and 1-epidechloroacutumine, together with three known alkaloids, acutumidine, acutumine, and dechloroacutumine, were isolated from the rhizomes of Menispermum dauricum and their structures established by spectral and chemical methods. The cytotoxicity of each compound against the growth of human cell lines was studied, and acutumine selectively inhibited T-cell growth.

  3. [Alkaloids of Annonaceae. XXIX. Alkaloids of Annona muricata].

    Science.gov (United States)

    Leboeuf, M; Legueut, C; Cavé, A; Desconclois, J F; Forgacs, P; Jacquemin, H

    1981-05-01

    From leaves, root - and stem - barks of Annona muricata L., seven isoquinoline alkaloids have been isolated: reticuline (main alkaloid), coclaurine, coreximine, atherosperminine, stepharine. Anomurine and anomuricine, two minor alkaloids, are new tetrahydrobenzylisoquinolines, with 5, 6, 7 substituted ring A. The phytochemical significance of these alkaloids is discussed.

  4. The background of the total synthesis of yeast alanine transfer RNA

    Institute of Scientific and Technical Information of China (English)

    QI GuoRong

    2010-01-01

    @@ The research findings concerning the total synthesis of yeast alanine transfer RNA (yeast alanine tRNA) were successively published in Chinese Science Bulletin (1982) and Science in China (1983) [1].The research work started in 1968 and was finished in November 1981.It was the first artificial synthesis of a nucleic acid molecule, which followed the first artificial synthesis of protein, crystalline bovine insulin, in China in 1965, both scientific milestones occurring in China.The composition, sequence and biological functions of the synthesized nucleic acid were identical to those of the natural yeast alanine tRNA.The research lasted for 13 years.From 1982 to 1984, one of the investigators in charge of the research Prof.

  5. Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodialis Eichler em roedores

    Directory of Open Access Journals (Sweden)

    Sueli Mendonça-Netto

    2008-06-01

    Full Text Available The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF of Cissampelos sympodialis Eichler (Menispermaceae on two animal models of depression: a forced swim test and b reserpine test. Treatment of mice with TTAF (12.5 mg/kg reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF de Cissampelos sympodialis Eichler (Menispermaceae em dois modelos animais de depressão: a teste do nado forçado e b teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modificou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.

  6. 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)

  7. [Alkaloids of Vinca rosea L. introduced to Western Georgia].

    Science.gov (United States)

    Vachnadze, N S; Kintsurashvili, L G; Suladze, T Sh; Bakuridze, A D; Vachnadze, V Iu

    2013-11-01

    Vinca roseae L. (Саtharanthus rosea (L.) G. Don) was introduced at Kobuleti experimental station of medical plants. The object of investigation was the plant material of Vinca roseae L. collected in May, 2005., September, 2006 and October, 2009. Total alkaloids were obtained in accordance with Atta- ur-Rachman method. The variability of the quantitative and qualitative composition of total alkaloids and vincaleikoblastin (VLB) fraction during vegetation was studied. It was established that the maximal content of total alkaloids and VLB fraction of Vinca roseae L. is accumulated in the phase of secondary flowering, hence the collecting of a plant material is recommended to be made during the aforesaid vegetation phase as for this period it is a rather high output of a raw material, alkaloid complex and VLB faction. Alkaloids vinkaleikoblastin, ajmalicine and new epimer tetrahydroalstonine with С3Н-α- orientation were yielded, separated and identified using modern physical-chemical and spectral methods (13С NMR).

  8. Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B.

    Science.gov (United States)

    Uesugi, Shun-ichiro; Watanabe, Tsubasa; Imaizumi, Takamichi; Ota, Yu; Yoshida, Keisuke; Ebisu, Haruna; Chinen, Takumi; Nagumo, Yoko; Shibuya, Masatoshi; Kanoh, Naoki; Usui, Takeo; Iwabuchi, Yoshiharu

    2015-12-18

    Irciniastatin A (a.k.a. psymberin) and irciniastatin B are members of the pederin natural product family, which have potent antitumor activity and structural complexity. Herein, we describe a full account of our total synthesis of (+)-irciniastatin A and (-)-irciniastatin B. Our synthesis features the highly regioselective Eu(OTf)3-catalyzed, DTBMP-assisted epoxide ring opening reaction with MeOH, which enabled a concise synthesis of the C1-C6 fragment, extensive use of AZADO (2-azaadamantane N-oxyl) and its related nitroxyl radical/oxoammonium salt-catalyzed alcohol oxidation throughout the synthesis, and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. In addition, for the synthesis of (-)-irciniastatin B, we achieved the C11-selective control of the oxidation stage via regioselective deprotection and AZADO-catalyzed alcohol oxidation. The synthetic irciniastatins showed high levels of cytotoxic activity against mammalian cells. Furthermore, chemical footprinting experiments using synthetic compounds revealed that the binding site of irciniastatins is the E-site of the ribosome.

  9. Total Synthesis of Ustiloxin D Utilizing an Ammonia-Ugi Reaction.

    Science.gov (United States)

    Brown, Aaron L; Churches, Quentin I; Hutton, Craig A

    2015-10-16

    Total synthesis of the highly functionalized cyclic peptide natural product, ustiloxin D, has been achieved in a convergent manner. Our strategy incorporates an asymmetric allylic alkylation to construct the tert-alkyl aryl ether linkage between the dopa and isoleucine residues. The elaborated β-hydroxydopa derivative is rapidly converted to a linear tripeptide through an ammonia-Ugi reaction. Subsequent cyclization and global deprotection affords ustiloxin D in six steps from a known β-hydroxydopa derivative.

  10. Total synthesis of (+)-discodermolide: a highly convergent fourth-generation approach.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; Xian, Ming; Hirose, Tomoyasu

    2005-04-28

    [structure: see text] A highly convergent, fourth-generation total synthesis of (+)-discodermolide (1), with a longest linear sequence of 17 steps and an overall yield of 9.0%, has been achieved. Highlighting the strategy is the efficient construction and sequential, bidirectional union of a linchpin comprising the C(9)-C(14) Wittig salt-vinyl iodide (-)-18. Importantly, Wittig salt generation proceeded in excellent yield under ambient pressure.

  11. Design, total synthesis, and evaluation of C13-C14 cyclopropane analogues of (+)-discodermolide.

    Science.gov (United States)

    Smith, Amos B; Xian, Ming; Liu, Fenghua

    2005-10-13

    [structure: see text] The design, total synthesis, and biological evaluation of two C13-C14-cyclopropyl analogues [(+)-1 and (+)-2] of (+)-discodermolide have been achieved. Key features of the syntheses include highly stereoselective, hydroxyl-directed cyclopropanations of vinyl iodides and higher order cuprate-mediated cross-coupling reactions between cyclopropyl iodides and alkyl iodides. Biological evaluation revealed that neither orientation of the cyclopropyl methylene completely substitutes for the C14 methyl found in (+)-discodermolide (3).

  12. 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.

  13. Zeolite-Based Organic Synthesis (ZeoBOS) of Acortatarin A: First Total Synthesis Based on Native and Metal-Doped Zeolite-Catalyzed Steps.

    Science.gov (United States)

    Wimmer, Eric; Borghèse, Sophie; Blanc, Aurélien; Bénéteau, Valérie; Pale, Patrick

    2017-01-31

    Similarly to polymer-supported assisted synthesis (PSAS), organic synthesis could be envisaged being performed by using zeolites, native or metal-doped, as heterogeneous catalysts. To illustrate this unprecedented Zeolite-Based Organic Synthesis (ZeoBOS), the total synthesis of acortatarin A was achieved through a novel strategy and using five out of eleven synthetic steps catalyzed by H- or metal-doped zeolites as catalysts. Notably, the formation of an yne-pyrrole intermediate with a copper-doped zeolite and the spiroketalization of an alkyne diol with a silver-doped zeolite have been developed as key steps of the synthesis.

  14. 壮药矮陀陀中总生物碱含量测定条件优选及不同产地药材含量比较%Optimization of the Content Determination Conditions of Total Alkaloids from Zhuang Medicine Munronia delavayi and Comparison of the Contents in M. delavayi from Different Producing Areas

    Institute of Scientific and Technical Information of China (English)

    马雯芳; 唐玉荣; 颜萍花; 曾祥燕; 蔡毅

    2016-01-01

    OBJECTIVE:To optimize the content determination conditions of total alkaloids from Zhuang medicine Munronia delavayi,and to determine the content of total alkaloids in M. delavayi from different producing areas. METHODS:With the con-tent of total alkaloids as index,using solvent amount,ultrasonic time,ultrasonic extraction times and pH value of buffer as fac-tors,the content determination conditions of total alkaloids from Zhuang medicine M. delavayi were optimized by orthogonal test. Optimized content determination conditions were adopted to determine the content of total alkaloids in M. delavayi from 18 produc-ing areas in different harvest time. RESULTS:The optimum content determination conditions were as follows as the amount of sol-vent(CHCl3)20 ml,ultrasonic processing for 3 times,lasting for 15 min each time,pH value of buffer 4.5. The contents of total alkaloids in M. delavayi from 18 producing areas were between 0.6-11.98 mg/g,showing great difference. M. delavayi from Long-lin county and Tianlin county harvested in Oct. had the lowest content of total alkaloids. CONCLUSIONS:Optimized content deter-mination condition can be used for the content determination of total alkaloids in Zhuang medicine M. delavayi and quality control of it. The content determination of total alkaloids in M. delavayi is related to producing area and harvest time.%目的:优选壮药矮陀陀中总生物碱的含量测定条件,并对不同产地药材进行含量比较。方法:采用正交试验法,以总生物碱含量为评价指标,以溶剂用量、超声时间、超声提取次数、缓冲液pH为考察因素,优选壮药矮陀陀中总生物碱含量测定的条件。采用优选的含量测定条件,测定18个产地不同采收季节药材的总生物碱含量。结果:优选的含量测定条件为溶剂用量(三氯甲烷)20 ml,超声处理3次,每次超声15 min,缓冲液pH为4.5。18个产地药材总生物碱含量在0.6~11.98 mg/g之间

  15. 3,4-桥环吲哚类生物碱的合成研究进展%Progress in Synthesis of 3,4-Fused Indole Alkaloids

    Institute of Scientific and Technical Information of China (English)

    单冬; 贾彦兴

    2013-01-01

    取代的吲哚类天然产物是自然界中普遍存在的一类杂环化合物,由于其具有广泛的生理活性,以及相当一部分作为重要的临床使用药物,100多年以来,吲哚的合成及官能团化一直是有机合成化学家关注的一个重要领域.在众多吲哚类生物碱中,含有3,4-桥环吲哚骨架的天然产物占据了相当一部分,由于其独特的结构和良好的生物活性,这些分子引起了有机合成化学家的广泛兴趣.重点概述了构建3,4-桥环骨架的主要合成方法和策略,并对一些方法在天然产物全合成中的应用作简要介绍.%The indole nucleus is one of the most important heterocycles for its presence in a vast number of bioactive natural products,pharmaceuticals,and agrochemicals.Due to their widest spectrum of biological activity and some of them have been used in clinical trials,construction and functionalization of indoles have attracted considerable interests from synthetic and medicinal chemists for over a hundred years.Among the naturally occurring indole alkaloids,those containing 3,4-fused indole skeleton possess a major part and have been especially considered attractive synthetic targets because of their unique structure and biological activities.This review emphasized on the methodologies and strategies of construction of 3,4-fused indole skeleton,and their application in total synthesis of natural products.

  16. Genotoxic effect of alkaloids

    Directory of Open Access Journals (Sweden)

    J. A. P. Henriques

    1991-01-01

    Full Text Available Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion in yeast diploid strain XS2316.

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

    Science.gov (United States)

    Kirschning, Andreas; Taft, Florian; Knobloch, Tobias

    2007-10-21

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

  18. Study on the Microwave-Assisted Extraction of the Total Steroidal Alkaloids from Solanum nigrum L.%微波辅助提取龙葵中总生物碱的研究

    Institute of Scientific and Technical Information of China (English)

    刘覃; 陈晓青; 蒋新宇; 吴升德

    2005-01-01

    本文对龙葵中总生物碱(Total steroidal alkaloids,TSA)的微波辅助提取(Microwave-assisted extraction,MAE)工艺、作用机理及对成分的结构影响进行了系统的研究.以酸性染料比色法为分析手段,设计正交试验得到了最佳提取工艺:以95%乙醇为溶剂,料液比1:20,在585W下提取8 min;用扫描电镜(SEM)对样品处理前后形貌进行了观察,揭示了微波作用机理与细胞结构变化有关.同时薄层色谱(TLC)、反相高效液相色谱(RP-HPLC)定性分析显示,微波对有效成分的结构没有造成影响.

  19. Extraction of Total Alkaloids from Pomegranate Peel Using Ultrasonic Coupled with Aqueous Two-phase Separation%超声集成双水相体系提取石榴皮中总生物碱的研究

    Institute of Scientific and Technical Information of China (English)

    吴佳; 解成喜

    2012-01-01

    The total alkaloids were extracted from Pomegranate Peel and determined with acid dye colorimtric method. By orthogonal test, the highest extraction yield was obtained when the amount of ammonium sulfate was 8. 0 g,the volume propanol was 20 mL,the alcohol/water ratio of the two-phase extraction system was 0. 8 and ultrasonic extraction time was 60 min. Under the optimized conditions,the extraction rate was 0. 559 mg/g with an average recovery of'100. &%.%研究了石榴皮中总生物碱的提取工艺并对其含量进行测定.以酸性染料比色法为分析手段,通过正交试验,探讨了影响总生物碱提取率因素的范围和最佳组合.石榴皮中总生物碱的最佳提取工艺条件为:硫酸铵8.0g、丙醇用量20 mL、醇水比为0.8∶1的双水相体系、超声时间60 min.在此条件下,石榴皮中总生物碱的平均提取率为0.559 mg/g,平均回收率为100.8%.

  20. Determination of Total Alkaloid in Semen Arecae by Acid Dye Colorimetry%酸性染料比色法测定槟榔中总生物碱的含量

    Institute of Scientific and Technical Information of China (English)

    徐洁

    2001-01-01

    采用酸性染料比色法测定槟榔中总生物碱的含量。槟榔碱在19.83~124.0μg范围内呈线性关系,回归方程为Y=8.960×10-3X-0.09062,r=0.9996。平均回收率为99.36%,RSD为1.87%(n=5)。该方法简便,灵敏,准确。%The method for the quantitative determination of total alkaloid in Semen Arecae by acid bye colorimetry was reported.A good linear correlation was found in the range of 19.83 to 124.0μg of arecoline. The regression equation was Y=8.960×103X-0.09062 and the correlation coefficient was 0.9996.The average recoverv was 99.36% and RSD 1.87%(n=5).This method is simple, sensitive, accurate.

  1. A novel ultra-performance liquid chromatography hyphenated with quadrupole time of flight mass spectrometry method for rapid estimation of total toxic retronecine-type of pyrrolizidine alkaloids in herbs without requiring corresponding standards.

    Science.gov (United States)

    Zhu, Lin; Ruan, Jian-Qing; Li, Na; Fu, Peter P; Ye, Yang; Lin, Ge

    2016-03-01

    Nearly 50% of naturally-occurring pyrrolizidine alkaloids (PAs) are hepatotoxic, and the majority of hepatotoxic PAs are retronecine-type PAs (RET-PAs). However, quantitative measurement of PAs in herbs/foodstuffs is often difficult because most of reference PAs are unavailable. In this study, a rapid, selective, and sensitive UHPLC-QTOF-MS method was developed for the estimation of RET-PAs in herbs without requiring corresponding standards. This method is based on our previously established characteristic and diagnostic mass fragmentation patterns and the use of retrorsine for calibration. The use of a single RET-PA (i.e. retrorsine) for construction of calibration was based on high similarities with no significant differences demonstrated by the calibration curves constructed by peak areas of extract ion chromatograms of fragment ion at m/z 120.0813 or 138.0919 versus concentrations of five representative RET-PAs. The developed method was successfully applied to measure a total content of toxic RET-PAs of diversified structures in fifteen potential PA-containing herbs.

  2. 北豆根总碱注射液抗实验性心律失常作用%Effects of Total Alkaloid of Menispermum Dauricum on Experimental Models of Dysrhythm

    Institute of Scientific and Technical Information of China (English)

    刘秀华; 韩福林

    2000-01-01

    采用五种实验动物心律失常模型观察了北豆根总碱(Total Alkaloid of Menispermum Dauricum,简写TAMD)注射液的抗心律失常作用.结果表明iv 5mg·kg-1TAMD对氯化钡诱发大鼠心律失常的治疗作用明显优于10mg·kg-1奎尼丁;对乌头碱诱发心律失常预防作用优于利多卡因;对抗哇巴因诱发豚鼠的心律失常与利多卡因相似;对氯仿诱发小鼠室颤有保护作用且优于奎尼丁;对大鼠冠脉结扎复灌引起心律失常有保护作用,与利多卡因作用相似.

  3. 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…

  4. 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...

  5. Total RNA-seq to identify pharmacological effects on specific stages of mRNA synthesis.

    Science.gov (United States)

    Boswell, Sarah A; Snavely, Andrew; Landry, Heather M; Churchman, L Stirling; Gray, Jesse M; Springer, Michael

    2017-03-06

    Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation. Compared to well-characterized elongation inhibitors that target CDK9, isoginkgetin caused RNA polymerase accumulation within a broader promoter-proximal band, indicating that elongation inhibition by isoginkgetin occurs after release from promoter-proximal pause. RNA-seq distinguished isoginkgetin and CDK9 inhibitors from topoisomerase I inhibition, which alters elongation across gene bodies. We were able to detect these and other specific defects in mRNA synthesis at low sequencing depth using simple metagene-based metrics. These metrics now enable total-RNA-seq-based screening for high-throughput identification of pharmacological effects on individual stages of mRNA synthesis.

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

    Science.gov (United States)

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

    2008-01-01

    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)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (−)-2, which also unambiguously established the absolute configuration of the natural product. PMID:17177450

  7. 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

  8. Analysis of Ergot Alkaloids

    OpenAIRE

    Colin Crews

    2015-01-01

    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). Ot...

  9. Total synthesis and structure–activity relationship studies of a series of selective G protein inhibitors

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Zhang, Hang; Underwood, Christina R.;

    2016-01-01

    G proteins are key mediators of G protein-coupled receptor signalling, which facilitates a plethora of important physiological processes. The cyclic depsipeptides YM-254890 and FR900359 are the only known specific inhibitors of the Gq subfamily of G proteins; however, no synthetic route has been...... reported previously for these complex natural products and they are not easily isolated from natural sources. Here we report the first total synthesis of YM-254890 and FR900359, as well as of two known analogues, YM-385780 and YM-385781. The versatility of the synthetic approach also enabled the design...... and synthesis of ten analogues, which provided the first structure–activity relationship study for this class of compounds. Pharmacological characterization of all the compounds at Gq-, Gi- and Gs-mediated signalling provided succinct information on the structural requirements for inhibition, and demonstrated...

  10. Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

    Science.gov (United States)

    Pereira, Claney L; Govindan, Subramanian

    2017-01-01

    The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations.

  11. Synthesis and antiviral and fungicidal activity evaluation of β-carboline, dihydro-β-carboline, tetrahydro-β-carboline alkaloids, and their derivatives.

    Science.gov (United States)

    Song, Hongjian; Liu, Yongxian; Liu, Yuxiu; Wang, Lizhong; Wang, Qingmin

    2014-02-05

    Six known β-carboline, dihydro-β-carboline, and tetrahydro-β-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 μg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 μg/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 μg/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 μg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibited good fungicidal activity against 14 kinds of fungi, especially compounds 4, 7, and 11.

  12. 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 c...

  13. A Novel Alkaloid from Stapelia hirsuta

    OpenAIRE

    SHABANA, Marwan; GONAID, Mariam; SALAMA, Maha Mahmoud; ABDEL-SATTAR, Essam

    2006-01-01

    A novel alkaloid (1,8,8-trimethyl-5,8-dihydro-1H-pyrano[3,4-b]pyridine-4,6-dione) was isolated from the chloroformic traction obtained from the total alcoholic extract of the aerial parts of Stapelia hirsuta L. In addition, apigenin, luteolin and b-sitosterol-3-O-b-D- glucopyranoside were also isolated.

  14. Ergot alkaloids decrease rumen epithelial blood flow

    Science.gov (United States)

    Two experiments were conducted to determine if ergot alkaloids affect blood flow to the absorptive surface of the rumen of steers. Steers (n=8 total) were pair-fed alfalfa cubes at 1.5× NEM and received ground endophyte-infected tall fescue seed (E+) or endophyte-free tall fescue seed (E-) via rumen...

  15. Absolute configuration of anti-HIV-1 agent (-)-concentricolide: total synthesis of (+)-(R)-concentricolide.

    Science.gov (United States)

    Chang, Chih-Wei; Chein, Rong-Jie

    2011-05-20

    The first enantioselective total synthesis of (+)-(R)-concentricolide, the enantiomer of an anti-HIV-1 agent isolated from Daldinia concentrica, from 2-iodophenol in 7 steps reveals the (S)-configuration for the natural form of the furanophthalide. The key features include an anionic ortho-Fries rearrangement to furnish 3-iodosalicylamide, facile construction of the benzofuran system employing the tandem Sonogashira coupling annulation reaction, directed ortho metalation to introduce a propanoyl group, as well as CBS reduction, establishing the stereocenter enantioselectively.

  16. Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

    Directory of Open Access Journals (Sweden)

    Richard J. Payne

    2013-07-01

    Full Text Available The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro.

  17. 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.

  18. 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.

  19. 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. PMID:27559415

  20. First total synthesis of 10α-hydroxy-4-muurolen-3-one and its C10-isomer

    Institute of Scientific and Technical Information of China (English)

    Fu Qiang Bi; Li Jing Fang; Chen Xi Zhang; Yu Lin Li

    2008-01-01

    An efficient synthetic route to muurolane type sesquiterpenes starting from (R)-carvone,employing allylic diazene rearrange-ment and the ring closing methesis (RCM) reaction as key steps,is described.The first asymmetric total synthesis of (-)-10α-hydroxy-4-muurolen-3-one B and (-)-10β-hydroxy-4-muurolen-3-one C was accomplished.Through the total synthesis,the absolute configurations of the natural products A,B and C were established.

  1. Belladonna Alkaloid Combinations and Phenobarbital

    Science.gov (United States)

    Belladonna alkaloid combinations and phenobarbital are used to relieve cramping pains in conditions such as irritable bowel syndrome and ... Belladonna alkaloid combinations and phenobarbital come as a regular tablet, a slow-acting tablet, capsule, and liquid to take ...

  2. 半夏总生物碱对人胃癌细胞增殖的抑制作用%Inhibitive effect of total alkaloids from Pinellia Ternate on the proliferation of human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    陈雅琳; 唐瑛; 王庆敏; 孙欢; 周茜

    2014-01-01

    Objective To observe the inhibitive effect of total alkaloids from Pinellia Ternate (TATP) on the proliferation on the human gastric cancer cell strain SGC-7901, and to investigate possible mechanism involved.Methods The inhibitive effect of different level TATP on the proliferation of SGC-7901 treated with TATP was monitored with the methyl thiazolil tetracolium colorimetic method and the plate clone formation assay.DNA damage of SGC-7901 cells induced by TATP was detected with the single cell gel electrophoresis (SCGE). Results Treated with TATP, the in vitro proliferation of SGC-7901 was significantly decreased, which was positively correlated with the dos-age of the drug and intervention time.Statistical significance could be seen, when it was compared with that of the control group (P<0.05). Single cell gel electrophoresis ( SCGE) indicated that significant differences could be seen in cell tail DNA contents , tail length and intensity of tail movement for the TATP experimental group and were dose-dependent (P<0.01).Conclusion A certain dosage of TATP could inhibit the proliferation of SGC-7901 in vitro, the mechanism of which might be correlated to the DNA damage induced by TATP .%目的:观察半夏总生物碱( total alkaloids from Pinellia Ternate,TATP)对人胃癌细胞株SGC-7901增殖抑制的影响,探讨其可能的作用机制。方法采用四甲基偶氮唑盐比色法及集落形成率实验,检测不同浓度的TATP对SGC-7901细胞株的生长抑制作用;应用单细胞凝胶电泳技术检测TATP导致SGC-7901细胞的DNA损伤情况。结果人胃癌细胞SGC-7901经TATP处理后,其体外增殖能力明显下降,且与药物的剂量、干预时间呈正相关,与对照组比较,差异均有统计学意义( P<0畅05或<0.01)。单细胞凝胶电泳( single cell gel electrophoresis , SCGE)中,TATP组细胞尾DNA含量、尾长及尾动量与对照组比较差异均有统计学意义(P<0.01),

  3. Inhibitory Effect of Total Alkaloids from Pinellia Ternate on the Proliferation of Human Breast Cancer cells%半夏总生物碱对人乳腺癌细胞增殖的抑制作用

    Institute of Scientific and Technical Information of China (English)

    孙欢; 唐瑛; 周茜; 王庆敏; 雷呈祥

    2012-01-01

    Objective To investigate the proliferation inhibition effect of total alkaloids from Pinellia ternate (TATP) on the human breast cancer line MDA-MB-435S. Methods The proliferation inhibition effect of different concentrations of TATP on the human breast cancer cell line MDA-MB-435S was measured by methyl thiazolil tetracolium colorimetic (MTT) method and plate clone formation assay. The DNA damage was detected by the single cell gel electro-phoresis (SCGE). Results The proliferation in MDA-MB-435S cell treated with TATP was decreased significantly compared with the control group and the proliferation inhibition was positively correlated to the TATP concentration and the reaction time. The IC50 of MDA-MB-435S cell incubated 24,48,72 hours with TATP were 98. 37 ^g/ml,52. 16 礸/ml and 33. 63 礸/ml respectively. Compared with the control group,the tail DNA content,the tail length and the tail movement of the TATP experimental groups were significantly different (P<0. 01) and presented a dose-effect relationship. Conclusion TATP could inhibit the proliferation of MDA-MB-435S cells in vitro,which might be correlated to the DNA damage induced by TAPT.%目的 探讨半夏总生物碱(total alkaloids from pinellia ternate,TATP)对人乳腺癌细胞株MDA-MB-435S增殖的影响.方法 采用四甲基偶氮唑盐(methyl thiazolil tetracolium,MTT)比色法以及集落形成率实验,检测不同浓度的TATP对MDA-MB-435S细胞株的生长抑制作用.应用单细胞凝胶电泳分析检测TATP导致MDA-MB-435S细胞的DNA损伤情况.结果 人乳腺癌细胞MDA-MB-435S经TATP处理后,其体外增殖能力受到明显抑制且与药物剂量、作用时间呈正相关,经TATP作用24、48、72 h后的半数抑制浓度分别为:98.37μg/ml、52.16 μg/ml、33.63μg/ ml.单细胞凝胶电泳(single cell gel electrophoresis,SCGE)中,TATP组细胞尾DNA含量、尾长及尾动量与对照组有统计学差异(P<0.01),且呈现浓度依赖性.结论 在体外培养

  4. 白益母草总生物碱聚乳酸-羟基乙酸共聚物微球的制备%Preparation of Poly( lactide-co-glycolide)Microspheres Containing Total Alkaloids of Panzeria alaschanica

    Institute of Scientific and Technical Information of China (English)

    陈晓北

    2015-01-01

    目的:优化蒙药白益母草总生物碱的聚乳酸-羟基乙酸共聚物(PLGA)微球的处方工艺,制备微球并对其进行质量考察.方法:采用复乳-液中干燥法制备白益母草总生物碱PLGA微球,以处方中PLGA质量浓度、聚乙烯醇(PVA)浓度及内水相/油相体积比为因素,以微球的载药量、包封率、收率的综合评分为指标,采用L9(34)正交试验优化制备微球的处方工艺,并考察微球形态、粒径及体外释药情况.结果:最优工艺为PLGA 200 mg/ml、PVA 2%、内水相/油相的体积比为1:5;验证试验中平均包封率为(83.2±2.4)%,平均载药量为(4.16±0.17)%,平均收率为(86.7±3.6)%,综合评分结果为(95.7±4.4)%,RSD均小于5.0%(n=3);制备的微球形态圆整,表面光滑,粒径分布均匀,平均粒径为(22.3±2.4)μm;微球24 h体外累积释放度为(82.3±3.5)%,符合一级释放模型(r=0.972 4).结论:优选工艺稳定;制备的微球具有良好的缓释性能,质量符合要求.%OBJECTIVE:To optimize the formulation and technology of poly(lactide-co-glycolide)(PLGA)microspheres con-taining total alkaloids of Panzeria alaschanica,and to prepare microspheres and conduct quality investigation. METHODS:PLGA microspheres containing total alkaloids of P. alaschanica (PTPM) was prepared by double emulsion-solvent evaporation method. The formulation of microspheres was optimized by L9(34) orthogonal design using mass concentration of PLGA,PVA concentra-tion,ratio of water phase to oil phase as factor,drug-loading amount,encapsulation efficiency,yield as index. The morphology, particle size and drug release of microspheres were all investigated. RESULTS:The optimal formulation was as follows as the mass concentration of PLGA 200 mg/ml,the concentration of PVA 2%,and the water phase-oil phase ratio 1:5. In validation test,aver-age encapsulation efficiency was(83.2±2.4)%,average drug-loading amount(4.16±0.17)%,average yield(86.7±3.6)%,and comprehensive score (95.7 ± 4

  5. Total synthesis, assignment of the relative and absolute stereochemistry, and structural reassignment of phostriecin (aka Sultriecin).

    Science.gov (United States)

    Burke, Christopher P; Haq, Nadia; Boger, Dale L

    2010-02-24

    A total synthesis of phostriecin (2), previously known as sultriecin (1), its structural reassignment as a phosphate versus sulfate monoester, and the assignment of its relative and absolute stereochemistry are disclosed herein. Key elements of the work, which provided first the originally assigned sulfate monoester 1 and then the reassigned and renamed phosphate monoester 2, relied on diagnostic (1)H NMR spectroscopic properties of the natural product for the assignment of relative and absolute stereochemistry as well as the subsequent structural reassignment, and a convergent asymmetric total synthesis to provide the unequivocal authentic materials. Key steps of the synthetic approach include a Brown allylation for diastereoselective introduction of the C9 stereochemistry, an asymmetric CBS reduction to establish the lactone C5-stereochemistry, diastereoselective oxidative ring expansion of an alpha-hydroxyfuran to access the pyran lactone precursor, and single-step installation of the sensitive Z,Z,E-triene unit through a chelation-controlled cuprate addition with installation of the C11 stereochemistry. The approach allows ready access to analogues that can now be used to probe important structural features required for protein phosphatase 2A inhibition, the mechanism of action defined herein.

  6. Total synthesis of woodrosin I--part 2: final stages involving RCM and an orthoester rearrangement.

    Science.gov (United States)

    Fürstner, Alois; Jeanjean, Fabien; Razon, Patrick; Wirtz, Conny; Mynott, Richard

    2003-01-03

    The completion of the first total synthesis of the complex resin glycoside woodrosin I (1) is outlined using the building blocks described in the preceding paper. Key steps involve the TMSOTf-catalyzed coupling of diol 2 with trichloroacetimidate 3 which leads to the selective formation of orthoester 5 rather than to the expected tetrasaccharide. Diene 5, on treatment with catalytic amounts of the Grubbs carbene complex 6 or the phenylindenylidene ruthenium complex 7, undergoes a high yielding ring closing olefin metathesis reaction (RCM) to afford macrolide 8. Exposure of the latter to the rhamnosyl donor 4 in the presence of TMSOTf under "inverse glycosylation" conditions delivers compound 9 by a process involving glycosylation of the sterically hindered 2'-OH group and concomitant rearrangement of the adjacent orthoester into the desired beta-glycoside. This transformation constitutes one of the most advanced applications of the Kochetkov glycosidation method reported to date. Cleavage of the chloroacetate followed by exhaustive hydrogenation completes the total synthesis of the targeted glycolipid 1.

  7. Anticonvulsant properties of the total alkaloid fraction of Rauvolfia ligustrina Roem. et Schult. in male mice Propriedades anticonvulsivantes da fração dos alcalóides totais de Rauvolfia ligustrina Roem. et Schult. em ratos machos

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2007-06-01

    Full Text Available Rauvolfia ligustrina Roem et. Schult (Apocynaceae, commonly known as "paratudo" and "arrebenta-boi" is a small tree found in Brazilian Northeastern. Previous studies have demonstrated depressant and anticonvulsant properties of the ethanol extract of Rauvolfia ligustrina. The aim of the present study was the determination of the lethal dose 50% (LD50 and the effects of total alkaloid fraction (TAF of the aerial parts of R. ligustrina in animal models of convulsion. It was found that the acute toxicity of TAF was 127.8 (112.5-145.2 mg/kg (i.p. in mice. TAF (20 mg/kg, ip significantly increased (p Rauvolfia ligustrina Roem. et Schult. (Apocynaceae é uma planta amplamente distribuída no Nordeste Brasileiro, rica em alcalóides indólicos, conhecida popularmente como "paratudo" e "arrebenta-boi". O presente estudo buscou avaliar a dose letal 50 % (DL50 da fração de alcalóides totais (FAT das partes aéreas da R. ligustrina e a sua possível atividade anticonvulsivantes em roedores. A FAT apresentou uma DL50, via intraperitoneal (i.p., de 127,8 (112,5-145,2 mg/kg e foi efetiva, na dose de 20 mg/kg (i.p., em proteger os animais das convulsões induzidas pelo pentilenotetrazol (PTZ e picrotoxina (PIC aumentando significativamente (p < 0,05 a latência para o aparecimento das convulsões, sendo um indicativo de um efeito anticonvulsivante.

  8. 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.

  9. Alkaloids from Hippeastrum papilio

    Directory of Open Access Journals (Sweden)

    Jaume Bastida

    2011-08-01

    Full Text Available Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl® for the treatment of Alzheimer’s disease (AD, is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11β-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11β-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine.

  10. 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.

  11. 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.

  12. Total Synthesis Confirms the Molecular Structure Proposed for Oxidized Levuglandin D2.

    Science.gov (United States)

    Cheng, Yu-Shiuan; Yu, Wenyuan; Xu, Yunfeng; Salomon, Robert G

    2017-02-24

    Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aβ1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins. In view of this high proclivity for covalent adduction, it is understandable that free LGs have never been detected in vivo. Recently a catabolite, believed to be an oxidized derivative of LGD2 (ox-LGD2), a levulinic acid hydroxylactone with prostanoid side chains, was isolated from the red alga Gracilaria edulis and detected in mouse tissues and in the lysate of phorbol-12-myristate-13-acetate-treated THP-1 cells incubated with arachidonic acid. Such oxidative catabolism of LGD2 is remarkable because it must be outstandingly efficient to prevail over adduction with proteins and because it requires a unique dehydrogenation. We now report a concise total synthesis that confirms the molecular structure proposed for ox-LGD2. The synthesis also produces ox-LGE2, which readily undergoes allylic rearrangement to Δ(6)-ox-LGE2.

  13. Total synthesis and structure-activity relationship studies of a series of selective G protein inhibitors

    Science.gov (United States)

    Xiong, Xiao-Feng; Zhang, Hang; Underwood, Christina R.; Harpsøe, Kasper; Gardella, Thomas J.; Wöldike, Mie F.; Mannstadt, Michael; Gloriam, David E.; Bräuner-Osborne, Hans; Strømgaard, Kristian

    2016-11-01

    G proteins are key mediators of G protein-coupled receptor signalling, which facilitates a plethora of important physiological processes. The cyclic depsipeptides YM-254890 and FR900359 are the only known specific inhibitors of the Gq subfamily of G proteins; however, no synthetic route has been reported previously for these complex natural products and they are not easily isolated from natural sources. Here we report the first total synthesis of YM-254890 and FR900359, as well as of two known analogues, YM-385780 and YM-385781. The versatility of the synthetic approach also enabled the design and synthesis of ten analogues, which provided the first structure-activity relationship study for this class of compounds. Pharmacological characterization of all the compounds at Gq-, Gi- and Gs-mediated signalling provided succinct information on the structural requirements for inhibition, and demonstrated that both YM-254890 and FR900359 are highly potent inhibitors of Gq signalling, with FR900359 being the most potent. These natural products and their analogues represent unique tools for explorative studies of G protein inhibition.

  14. Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.

    Science.gov (United States)

    Glinkerman, Christopher M; Boger, Dale L

    2016-09-28

    Although it has been examined for decades, no general approach to catalysis of the inverse electron demand Diels-Alder reactions of heterocyclic azadienes has been introduced. Typically, additives such as Lewis acids lead to nonproductive consumption of the electron-rich dienophiles without productive activation of the electron-deficient heterocyclic azadienes. Herein, we report the first general method for catalysis of such cycloaddition reactions by using solvent hydrogen bonding of non-nucleophilic perfluoroalcohols, including hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), to activate the electron-deficient heterocyclic azadienes. Its use in promoting the cycloaddition of 1,2,3-triazine 4 with enamine 3 as the key step of a concise total synthesis of methoxatin is described.

  15. 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.

  16. Aporphine alkaloid contents increase with moderate nitrogen supply in Annona diversifolia Saff. (Annonaceae) seedlings during diurnal periods.

    Science.gov (United States)

    Orozco-Castillo, José Agustín; Cruz-Ortega, Rocío; Martinez-Vázquez, Mariano; González-Esquinca, Alma Rosa

    2016-10-01

    Aporphine alkaloids are secondary metabolites that are obtained in low levels from species of the Annonaceae family. Nitrogen addition may increase the alkaloid content in plants. However, previous studies published did not consider that nitrogen could change the alkaloid content throughout the day. We conducted this short-term study to determine the effects of nitrogen applied throughout the diurnal period on the aporphine alkaloids via measurements conducted on the roots, stems and leaves of Annona diversifolia seedlings. The 60-day-old seedlings were cultured with the addition of three levels of nitrogen (0, 30 and 60 mM), and alkaloid extracts were analysed using high-performance liquid chromatography. The highest total alkaloid content was measured in the treatment with moderate nitrogen supply. Further, the levels of aporphine alkaloids changed significantly in the first few hours of the diurnal period. We conclude that aporphine alkaloid content increased with moderate nitrogen supply and exhibited diurnal variation.

  17. Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C-H Olefination.

    Science.gov (United States)

    Zhang, Zhongyin; Wang, Jinxin; Li, Jian; Yang, Fan; Liu, Guodu; Tang, Wenjun; He, Weiwei; Fu, Jian-Jun; Shen, Yun-Heng; Li, Ang; Zhang, Wei-Dong

    2017-03-08

    Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C-H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines were evaluated.

  18. 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...

  19. Plasma Concentration and Tissue Distribution of Total Alkaloids of Lianzixin after Intragastric and Intravenous Administration in Rats%莲心总碱在大鼠体内的血药浓度及组织分布

    Institute of Scientific and Technical Information of China (English)

    黄颖; 班翊; 胡本容; 王嘉陵; 向继洲

    2006-01-01

    目的研究大鼠灌胃及静脉注射莲心总碱(Total alkaloids of Lianzixin,TAL)的血药浓度和组织分布.方法给予TAL后,采用反相高效液相色谱法检测各时间点血浆和组织药物浓度,用DAS(drug and statistics)程序拟合房室模型并计算药代动力学参数.结果静脉注射TAL20 mg/kg,药时曲线符合三室模型,其主要药代动力学参数为:分布t1 2α为0.367 min,消除t1 2γ为841.597 min,血浆清除率(CL)为2.336 L/min,曲线下面积AUC0 1080和AUC0分别为639.392和823.754(mg·min)/L,MRT0为866.354 min;灌胃TAL20 mg/kg,曲线下面积AUC0 1080和AUC0分别为508.578和787.035(mg·min)/L,MRT0为1466.040 min.计算所得TAL的绝对生物利用度为80%.TAL20mg/kg灌胃后,迅速分布至各主要器官组织,其中以肝浓度最高;肺、心次之,脑组织最低.肝浓度在30 min有一谷值,而此时其他各组织的浓度则有所上升.与灌胃不同,静脉注射TAL以肺中浓度最高,其次为心、肾.5 min时,心、肺、肾组织各出现一浓度峰值,随后下降,4 h时又可见药物浓度回升.结论TAL吸收迅速,分布广泛,Vc较大,t1 2γ较长.除脑分布较少外,其他脏器的浓度均远高于血浆药物浓度.

  20. A short enantioselective total synthesis of the fundamental pentacyclic triterpene lupeol.

    Science.gov (United States)

    Surendra, Karavadhi; Corey, E J

    2009-10-07

    The first enantioselective synthesis of lupeol has been developed by applying two carefully crafted cation-pi cyclization stages to generate the pentacyclic structure with complete stereocontrol. The synthesis (Scheme 1) is noteworthy because of its brevity and also because it solves a longstanding problem in the field of natural product synthesis.

  1. Transgenic and mutation-based suppression of a berberine bridge enzyme-like (BBL) gene family reduces alkaloid content in field-grown tobacco.

    Science.gov (United States)

    Lewis, Ramsey S; Lopez, Harry O; Bowen, Steve W; Andres, Karen R; Steede, William T; Dewey, Ralph E

    2015-01-01

    Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels.

  2. Experimental study on long-term toxicity of sustained-release dropping pills of Rhynchophylla total alkaloids in rats%钩藤总碱缓释滴丸的长期毒性实验研究

    Institute of Scientific and Technical Information of China (English)

    王盟; 孙清海; 刘卫

    2014-01-01

    Objective To observe the long-term toxicity of sustained-release dropping pills of Rhynchophylla total alkaloids in rats.Methods 80 Wistar rats were randomly divided into high dose group, middle dose group, low dose group and normal group. The rats were consecutively drenched for 12 weeks. The general status of the animals was observed daily in medication duration and body weight, daily appetite, quantity were recorded every 2 weeks. All animals were sacrificed on drenched 12 weeks and 2 weeks after discontinuation, then the content of WBC, RBC, Hb, PLT, LYM, NEU and ALT, AST, ALP, BUN, Cr were detected. Ratio of viscera was measured and the major organs were examined by the pathology.Results Continuous intragastric administration for 12 weeks after high dose group rats, poor diet, weight growth was slow;no significant changes of Hematology was found;The ALT, AST and ALP of high dose group rats increased[respectively(77.5±11.9)U/L,(210.4±21.7)U/L,(220.6±19.8)U/L], compared with the blank control group[respectively(55.2±12.1)U/L,(180.4±21.3)U/L,(190.3±22.6)U/L], the difference was statistically significant(P<0.05). The ratio of liver body in high dose group(3.86±0.29)was higher than the control group(3.52±0.25), the difference was statistically significant(P<0.05). And liver degeneration, focal necrosis was found.Conclusion The main chronic toxic damage is liver damage caused by sustained-release dropping pills of Rhynchophylla total alkaloids of long-term large delivery.%目的:探讨钩藤总碱(RTA)缓释滴丸的长期毒性。方法将80只Wister大鼠按体质量随机分为空白对照组、RTA缓释滴丸高、中、低剂量组,每组20只。每天观察大鼠的一般状态、每2周记录一次体质量、日食量。连续灌胃12周后和停药2周后分别检测大鼠白细胞(WBC)、红细胞(RBC)、血红蛋白(Hb)、血小板(PLT)、淋巴细胞(LYM)、中性粒细胞(NEU)等血液学

  3. INHIBITORY EFFECTS OF THE ALKALOIDS FROM Radix Caulophylli ON THE PROLIFERATION OF HUMAN VASCULAR ENDOTHELIAL CELL

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To find an angiogenetic inhibitor from Radix Caulophylli (RC). Methods The extract of Radix Caulophylli was obtained by using 95% alcohol in water as solvent. Then, the total alkaloids of Radix Caulophylli was isolated from the extract by using a positive ion exchange resin column. An active part was found by a screening model of cell membrane chromatography (CMC) and further tested by the MTT method with emodin as a control. Results The total alkaloids of Radix Caulophylli was the active part by CMC and could significantly inhibit proliferation of ECV304 cells in MTT test. The inhibitory rate was 56.06% while the concentration of the total alkaloids of Radix Caulophylli was 19.63μg/mL. Conclusion The total alkaloids from Radix Caulophylli may be a new angiogenetic inhibitor, and mechanism of the total alkaloids on inhibitory angiogenesis still need to be further investigated.

  4. 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.

  5. Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin.

    Science.gov (United States)

    Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay; Weiss, Michael A; Eitel, Simon H; Meier, Thomas; Schoenleber, Ralph O; Kent, Stephen B H

    2017-01-31

    We have systematically explored three approaches based on 9-fluorenylmethoxycarbonyl (Fmoc) chemistry solid phase peptide synthesis (SPPS) for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the "hybrid method", in which maximally protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[O-β-(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester-linked polypeptide chain of ester insulin was the use of unprotected peptide-thioester segments, prepared from peptide-hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High-resolution X-ray crystallography confirmed the disulfide pairings and three-dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies could yield an efficient total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS.

  6. 雷公藤药材中6种有效成分以及总二萜内酯、总生物碱、总三萜的含量测定%Determination of six effective components, total diterpenoids, total alkaloids and total triterpenes in Tripterygium wilfordii Hook.f.

    Institute of Scientific and Technical Information of China (English)

    张茹萍; 何昱; 石森林; 钱家健; 范永升

    2013-01-01

    then changed to 210nm after 65 minute; The flow rate was 0.75ml/min and the analytic time was 80min, which was used to determine the six effective components in samples produced by ten different areas. Using triptolide, wilforine and tripterine as the contrast, total diterpenoids, total alkaloids and total triterpenes was determined by UV-Vis spectrophotometry. Results: There were significant differences of effective components and effective parts in Tripterygium wilfordii Hook. f. from different areas. For example, the highest content of wilforgine was about 291.6 times of the lowest one, while the highest content of the total diterpenoids was about 34.7 times of the lowest one. Conclusion: The method is in good reproducibility, precision and stability and is fit to determine the six effective ingredients in Tripterygium wilfordii Hook. f. At the same time, significant content difference has also been shown among different areas. It is very important to control the quality with multi-index for clinic safety.

  7. Quinolizidine alkaloids from Lupinus lanatus

    Science.gov (United States)

    Neto, Alexandre T.; Oliveira, Carolina Q.; Ilha, Vinicius; Pedroso, Marcelo; Burrow, Robert A.; Dalcol, Ionara I.; Morel, Ademir F.

    2011-10-01

    In this study, one new quinolizidine alkaloid, lanatine A ( 1), together with three other known alkaloids, 13-α- trans-cinnamoyloxylupanine ( 2), 13-α-hydroxylupanine ( 3), and (-)-multiflorine ( 4) were isolated from the aerial parts of Lupinus lanatus (Fabaceae). The structures of alkaloids 1- 4 were elucidated by spectroscopic data analysis. The stereochemistry of 1 was determined by single crystal X-ray analysis. Bayesian statistical analysis of the Bijvoet differences suggests the absolute stereochemistry of 1. In addition, the antimicrobial potential of alkaloids 1- 4 is also reported.

  8. Alkaloids from single skins of the Argentinian toad Melanophryniscus rubriventris (ANURA, BUFONIDAE): An unexpected variability in alkaloid profiles and a profusion of new structures.

    Science.gov (United States)

    Garraffo, H Martin; Andriamaharavo, Nirina R; Vaira, Marcos; Quiroga, María F; Heit, Cecilia; Spande, Thomas F

    2012-12-01

    GC-MS analysis of single-skins of ten Melanophryniscus rubriventris toads (five collections of two toads each) captured during their breeding season in NW Argentina has revealed a total of 127 alkaloids of which 56 had not been previously detected in any frog or toad. Included among these new alkaloids are 23 new diastereomers of previously reported alkaloids. What is particularly distinguishing about the alkaloid profiles of these ten collections is the occurrence of many of the alkaloids, whether known or new to us, in only one of the ten skins sampled, despite two skins being obtained from each breeding site of the five populations. Many of the alkaloids are of classes known to have structures with branched-chains (e.g. pumiliotoxins and tricyclic structures) that are considered to derive from dietary mites. A large number of previously reported and new alkaloids are also of unclassified structures. Only a very few 3,5-disubstituted-indolizidine or -pyrrolizidine alkaloids are observed that have a straight-chain carbon skeleton and are likely derived from ant prey. The possible relationship of these collections made during the toad's brief breeding episodes to sequestration of dietary arthropods and individual alkaloid profiles is discussed.

  9. C ring may be dispensable for β-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of β-carboline alkaloids.

    Science.gov (United States)

    Huang, Yuanqiong; Liu, Yongxian; Liu, Yuxiu; Song, Hongjian; Wang, Qingmin

    2016-02-01

    According to our previous work and the latest research on the biosynthesis of β-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of β-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure-activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV); especially (S)-2-amino-3-(1H-indol-3-yl)-N-octylpropanamide (4) (63.3±2.1%, 67.1±1.9%, 68.7±1.3%, and 64.5±3.1%, 500μg/mL) exhibited the best antiviral activity both in vitro and in vivo. Compound 4 was chosen for the field trials and the acute oral toxicity test, the results showed that the compound exhibited good anti-TMV activity in the field and low acute oral toxicity. We also found that these compounds showed antifungal activities and insecticidal activities.

  10. Total synthesis of rodgersinine A and B%Rodgersinine A和B的全合成

    Institute of Scientific and Technical Information of China (English)

    苗强; 谢新刚; 张基勇; 厍学功; 潘鑫复

    2007-01-01

    目的 合成苯并二氧六环类新木脂素.方法 综合使用多种有机合成反应来合成Rodgersinine A,4-(3-甲基-7-(E)-1-丙烯基-2,3-二氢-1,4-二氧六环)-1,2-苯二酚和Rodgersinine B,4-(3-甲基-7-(1-丙炔基)-2,3-二氢-1,4-二氧六环)-1,2-苯二酚.结果 首次合成了目标分子Rodgersinine A和B.结论 本文建立的合成方法可用于苯并二氧六环类新木脂素的合成.%Aim Syntheses of benzodioxane neolignans. Method The SN2 reaction and Corey-Fuchs reaction was used to synthesize Rodgersinine A, 4-[3-methyl-7-[(E)-1-propenyl-2, 3-dihydro-1, 4-benzodioxin-2-yl]-1, 2-benzenediol (1) and Rodgersinine B, 4- [3-methyl-7-(1-propynyl)-2, 3-dihydro- 1, 4-benzodioxin-2-yl]-1, 2-benzenediol (2). Results Total synthesis ofRodgersinine A and B was first completed.Conclusion A useful method for constructing benzodioxane neolignans by the SN2 reaction is achieved.

  11. Pyrrolizidine alkaloids pyrrolams A-D: A survey of synthetic efforts, biological activity, and studies on their stability

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Tilve, S.G.

    Pyrrolam A is a microbial metabolite, structurally related to plant alkaloids of the necine-type, and was isolated from the bacterial strain of Streptomyces olivaceus along with the related alkaloids pyrrolams B-D. The synthesis of (S)- and (R...

  12. A 11-Steps Total Synthesis of Magellanine through a Gold(I)-Catalyzed Dehydro Diels-Alder Reaction.

    Science.gov (United States)

    McGee, Philippe; Bétournay, Geneviève; Barabé, Francis; Barriault, Louis

    2017-01-12

    We have developed an innovative strategy for the formation of angular carbocycles via a gold(I)-catalyzed dehydro Diels-Alder reaction. This transformation provides rapid access to a variety of complex angular cores in excellent diastereoselectivities and high yields. The usefulness of this Au(I) -catalyzed cycloaddition was further demonstrated by accomplishing a 11-steps total synthesis of (±)-magellanine.

  13. Two new cytotoxic furoquinoline alkaloids isolated from Aegle marmelos (Linn.) Correa

    DEFF Research Database (Denmark)

    Mohammed, Magdy M D; Ibrahim, Nabaweya A.; El-Sakhawy, Fatma S.

    2016-01-01

    Two new cytotoxic furoquinoline alkaloids were isolated from the leaves of Aegle marmelos (Linn.) Correa; one from the total alkaloidal fraction (acid/base shake-out method) of the CHCl3 extract and identified as 7,8-dihydroxy-4-hydrofuroquinoline and named trivially as Aegelbine-A. The other new...... alkaloid isolated from the pet. ether extract and identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline and named trivially as Aegelbine-B, together with a known alkaloid; aegeline and a known phenolic acid; ρ-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D...

  14. Antitumor effect of total alkaloids from Aconiti Lateralis Radix Praeparata on breast cancer in mice%附子总生物碱对乳腺癌小鼠的抗肿瘤作用

    Institute of Scientific and Technical Information of China (English)

    张亚平; 杜钢军; 孙婷; 李佳桓; 刘伟杰; 王莹莹

    2012-01-01

    目的 观察附子总生物碱对二甲基苯葸诱导的乳腺癌小鼠体征、部分血液学指标及肿瘤的影响.方法 小鼠分为对照组、模型组、附子总生物碱组.模型组小鼠每天sc二甲基苯蒽橄榄油溶液50 mg/kg,每周2次、连续5周,建立乳腺癌模型,给药组在每天给予二甲基苯蒽的同时,给予附子总生物碱2 mg/kg,观察实验期间各组小鼠乳腺肿瘤的潜伏期、发生率、外观、体温和外耳微循环变化,检测血清中雌二醇和孕酮水平、红细胞Na+,K+-ATP酶和Ca2+,Mg2+-ATP酶活性及血液流变学指标,综合评价附子总生物碱对小鼠乳腺癌的影响.结果 模型组小鼠随给药时间的延长逐渐出现畏寒喜暖、蜷缩少动、体温下降、外耳微循环受阻状况,同时血中雌二醇和孕酮水平升高,红细胞ATP酶活性降低,全血黏度及红细胞聚集指数增高;附子总生物碱可以显著改善上述指标变化,阻止肿瘤生长.结论 二甲基苯葸诱导的乳腺癌小鼠表现为体寒血瘀体征,附子总生物碱能改善这些症状,阻止肿瘤进展.%To investigate the effects of total alkaloids from Aconiti Lateralis Radix Praeparata (TAALRP) on the manifestation of breast cancer induced by 7, 12-dimethylbenzanthracene (DMBA), some hematological indexes, and tumor growth in mice. Methods The mice were divided into control, model, and TAALRP groups. Mice in the model group were sc injected with DMBA (50 mg/kg in olive oil) twice weekly for five weeks to establish a breast cancer model; Mice in TAALRP group were simultaneously ig administrated with TAALRP (2 mg/kg). The changes in tumorigenic latency, incidence, appearance, body temperature, and auricle microcirculation were observed in carcinogenic process; The levels of estradiol and progesterone in serum, the activities of erythrocytic Na+, K+-ATPase and Ca2,Mg2+-ATPase, and hemorrheologic indexes were detected. The effects of TAALRP on breast cancer in mice were

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

    Science.gov (United States)

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

    2013-03-01

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

  16. Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone.

    Science.gov (United States)

    Aussedat, Baptiste; Fasching, Bernhard; Johnston, Eric; Sane, Neeraj; Nagorny, Pavel; Danishefsky, Samuel J

    2012-02-22

    Described herein is the first total chemical synthesis of the unique α-subunit of the human glycoprotein hormone (α-hGPH). Unlike the biologically derived glycoprotein hormones, which are isolated as highly complex mixtures of glycoforms, α-hGPH obtained by chemical synthesis contains discrete homogeneous glycoforms. Two such systems have been prepared. One contains the disaccharide chitobiose at the natural N-glycosylation sites. The other contains dodecamer oligosaccharides at these same sites. The dodecamer sugar is a consensus sequence incorporating the key features associated with human glycoproteins.

  17. Concise Asymmetric Construction of C2 -symmetric 1,9-Diarylnonanoids Using a Hypervalent Silicon Complex: Total Synthesis of (-)-Ericanone.

    Science.gov (United States)

    Kotani, Shunsuke; Kai, Kosuke; Shimoda, Yasushi; Hu, Hao; Gao, Shen; Sugiura, Masaharu; Ogasawara, Masamichi; Nakajima, Makoto

    2016-02-01

    By using a phosphine oxide-catalyzed enantioselective double aldol reaction, we achieved the concise construction of C2 -symmetric 1,9-diarylnonanoids, enabling the synthesis of (-)-ericanone from p-hydroxybenzaldehyde in 6 steps with 65 % overall yield. The enantioselective double aldol reaction is useful for establishing C2 -symmetric 1,9-diaryl-3,7-dihydroxy-5-nonanones with a single operation. Furthermore, the use of o-nosyl-protected p-hydroxybenzaldehyde and a 4,4'-disubstituted BINAP dioxide catalyst dramatically improved the reactivity and selectivity in the double aldol reaction, enabling the total synthesis of (-)-ericanone with high yield and with excellent enantiopurity.

  18. Concise synthesis of the hasubanan alkaloid (±)-cepharatine A using a Suzuki coupling reaction to effect o,p-phenolic coupling.

    Science.gov (United States)

    Magnus, Philip; Seipp, Charles

    2013-09-20

    Suzuki coupling of 10 and 11 resulted in 9, which was O-alkylated to provide 12. Treatment of 12 with CsF in DMF resulted in the formation of the completed core structure 13 in a single step. Reductive amination of 13 completed the synthesis of (±)-cepharatine A, 4.

  19. Alkaloids from Galanthus nivalis.

    Science.gov (United States)

    Berkov, Strahil; Codina, Carles; Viladomat, Francesc; Bastida, Jaume

    2007-07-01

    Phytochemical studies on Galanthus nivalis of Bulgarian origin resulted in the isolation of five compounds: 11-O-(3'-hydroxybutanoyl)hamayne, 3,11-O-(3',3''-dihydroxybutanoyl)hamayne, 3-O-(2''-butenoyl)-11-O-(3'-hydroxybutanoyl)hamayne, 3,11,3''-O-(3',3'',3'''-trihydroxybutanoyl)hamayne, and 2-O-(3'-acetoxybutanoyl)lycorine, together with five known alkaloids: ungeremine, lycorine, tazettine, hamayne, and ismine. Their structures were determined by (1)H and (13)C NMR spectroscopy and two-dimensional (1)H-(1)H and (1)H-(13)C chemical shift correlation experiments.

  20. 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.

  1. An Improved Method of Total Synthesis of 2-Methoxypodocarpane-8,11,13-triene

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    12-Methoxypodocarpane-8,11,13-triene 1, the key intermediate in the synthesis of some important diterpenes, was synthesized in an efficient way, which has the characteristics of short route, simple operation and high yield.

  2. Alkaloid variation in New Zealand kōwhai, Sophora species.

    Science.gov (United States)

    McDougal, Owen M; Heenan, Peter B; Jaksons, Peter; Sansom, Catherine E; Smallfield, Bruce M; Perry, Nigel B; van Klink, John W

    2015-10-01

    Alkaloid contents of leaf and seed samples of eight species of Sophora native to New Zealand, plus Sophora cassioides from Chile are reported. Fifty-six leaf and forty-two seed samples were analysed for alkaloid content by proton nuclear magnetic resonance spectroscopy, which showed major alkaloids as cytisine, N-methyl cytisine and matrine. GC analyses quantified these and identified further alkaloid components. The alkaloids identified were cytisine, sparteine, and matrine-types common to Sophora from other regions of the world. Cytisine, N-methyl cytisine, and matrine were generally the most abundant alkaloids across all species with seeds containing the highest concentrations of alkaloids. However, there was no clear taxonomic grouping based on alkaloid composition. A quantitative analysis of various parts of two Sophora microphylla trees showed that the seeds were the richest source of alkaloids (total 0.4-0.5% DM), followed by leaf and twig (0.1-0.3%) and then bark (0.04-0.06%), with only low amounts (<0.02%) found in the roots. This study represents the most comprehensive phytochemical investigation of New Zealand Sophora species to date and presents data for three species of Sophora for which no prior chemistry has been reported.

  3. Toxicity of Total Alkaloid from Tripterygium wilfordii Hook against Mythimna separata (Walker)and Its Effects of on AChE and Ach%雷公藤总生物碱对粘虫幼虫的毒力及对乙酰胆碱酯酶和乙酰胆碱的影响

    Institute of Scientific and Technical Information of China (English)

    周琳

    2011-01-01

    雷公藤生物碱是雷公藤Tripterygium wilfordii Hook中的主要杀虫活性物质.为进一步阐明雷公藤总生物碱的杀虫活性及杀虫作用机理提供线索和依据,研究采用载毒叶片法测定了雷公藤总生物碱对粘虫(Mythimna separata (Walker))三龄幼虫的胃毒毒力,观察了粘虫五龄幼虫的中毒症状,并测定了其对不同中毒阶段粘虫五龄幼虫头部乙酰胆碱酯酶(AChE)活性和乙酰胆碱(ACh)含量的影响.结果表明,雷公藤总生物碱对粘虫三龄幼虫48,72,96,120 h的胃毒LC50分别为306.39,216.12,157.18,129.92 mg/L;试虫中毒后行动迟缓,停止取食,继而软瘫麻痹(即麻醉),后复苏(或死亡),复苏试虫可再次取食、麻醉、复苏(或死亡),如此反复,直止死亡;雷公藤总生物碱对各中毒期试虫AChE无明显的抑制或激活作用;麻醉期试虫体内ACh的相对含量与同期对照无显著差异,复苏期有所下降.%Alkaloid is the main insecticidal composition in Tripterygium wilfordii Hook,a famous insecticidal plant. In order to study its insecticidal activites and mechanism ,the stomach toxicity of the total alkaloid against larvae of Mythimna separata Walker was tested, their toxicity symptoms were observed, and its effects on the activities of AChE and the content of ACh of larval heads in different toxicity stages were assayed. The results showed the stomach toxicity LD50 values of the total alkaloid against the 3rd instar larvae of M. separata in 24,48,96 and 120 h post treatment were 306.39,216.12,157.18 and 129. 92 mg/L. In vivo toxicity symptoms were characterized by a definite sequence of events, starting with moving slowly,stopping feeding, flaccid paralysis and recovering or death. Anabiotic insects started feeding ,were paralyzed, recovered or died again and up to death. It was presumed the total alkaloid from T. wilfordii influenced the nerve system of insects. AChE was not strongly inhibited or activated by the total alkaloid

  4. Transcription factors in alkaloid biosynthesis.

    Science.gov (United States)

    Yamada, Yasuyuki; Sato, Fumihiko

    2013-01-01

    Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.

  5. Concise Total Synthesis of Lundurines A-C Enabled by Gold Catalysis and a Homodienyl Retro-Ene/Ene Isomerization.

    Science.gov (United States)

    Kirillova, Mariia S; Muratore, Michael E; Dorel, Ruth; Echavarren, Antonio M

    2016-03-23

    The total synthesis of lundurines A-C has been accomplished in racemic and enantiopure forms in 11-13 and 12-14 steps, respectively, without protection/deprotection of functional groups, by a novel tandem double condensation/Claisen rearrangement, a gold(I)-catalyzed alkyne hydroarylation, a cyclopropanation via formal [3 + 2] cycloaddition/nitrogen extrusion, and a remarkable olefin migration through a vinylcyclopropane retro-ene/ene reaction that streamlines the endgame.

  6. 1,6-asymmetric induction in boron-mediated aldol reactions: application to a practical total synthesis of (+)-discodermolide.

    Science.gov (United States)

    Paterson, Ian; Delgado, Oscar; Florence, Gordon J; Lyothier, Isabelle; Scott, Jeremy P; Sereinig, Natascha

    2003-01-01

    By relying solely on substrate-based stereocontrol, a practical total synthesis of the microtubule-stabilizing anticancer agent (+)-discodermolide has been realized. This exploits a novel aldol bond construction with 1,6-stereoinduction from the boron enolate of (Z)-enone 3 in addition to aldehyde 2. The 1,3-diol 7 is employed as a common building block for the C(1)-C(5), C(9)-C(16), and C(17)-C(24) subunits. [reaction--see text

  7. Concise Total Synthesis of Lundurines A–C Enabled by Gold Catalysis and a Homodienyl Retro-Ene/Ene Isomerization

    Science.gov (United States)

    2016-01-01

    The total synthesis of lundurines A–C has been accomplished in racemic and enantiopure forms in 11–13 and 12–14 steps, respectively, without protection/deprotection of functional groups, by a novel tandem double condensation/Claisen rearrangement, a gold(I)-catalyzed alkyne hydroarylation, a cyclopropanation via formal [3 + 2] cycloaddition/nitrogen extrusion, and a remarkable olefin migration through a vinylcyclopropane retro-ene/ene reaction that streamlines the endgame. PMID:26963149

  8. Total Synthesis of ( - )-Kaerophyllin, ( - )-Hinokinin and (±)-Iso-hinokinin

    Institute of Scientific and Technical Information of China (English)

    夏亚穆; 梁其任; 王小龙; 曹小平; 潘鑫复

    2003-01-01

    A convenient and rapid approach for the syntheses of (-)-kaerophyllin (1), (-)-hinokinin (2) and (±)-isohinokinin (3) was described. The key steps were involved in condensation of aromatic aldehyde and alkylation of the resulting ester to give the complete skeleton of dibenzylbutyrolactone-lignan. Hydrolysis, followed by resolution with quinine, reduction and when appropriate, oxidation gave the title compound. The asynunetric total synthesis of the kaerophyllin (1) was reported for the first tlme.

  9. 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.

  10. 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.

  11. Total Synthesis of (-)-Doliculide, Structure-Activity Relationship Studies and Its Binding to F-Actin

    NARCIS (Netherlands)

    Matcha, Kiran; Madduri, Ashoka V. R.; Roy, Sayantani; Ziegler, Slava; Waldmann, Herbert; Hirsch, Anna K. H.; Minnaard, Adriaan J.

    2012-01-01

    Actin, an abundant protein in most eukaryotic cells, is one of the targets in cancer research. Recently, a great deal of attention has been paid to the synthesis and function of actin-targeting compounds and their use as effective molecular probes in chemical biology. In this study, we have develope

  12. First total synthesis of justicidone, a p-quinone-lignan derivative from Justicia hyssopifolia.

    Science.gov (United States)

    Boluda, Carlos J; López, Hermelo; Pérez, José A; Trujillo, Juan M

    2005-08-01

    The first synthesis of justicidone (4-(1',3'-Benzodioxol-5'-yl)-6-methoxynaphtho[2,3-c]furan-1,5,8(3H)-trione) was carried out from piperonal, as a starting compound, through a lineal process using well known reactions.

  13. Total Synthesis of the Antimicrotubule Agent (+)-Discodermolide Using Boron-Mediated Aldol Reactions of Chiral Ketones.

    Science.gov (United States)

    Paterson; Florence; Gerlach; Scott

    2000-01-01

    With a similar mechanism of action to taxol, the title compound 1 is a particularly promising candidate for development in cancer chemotherapy. This efficient synthesis, based on stereocontrolled aldol reactions, should help to overcome the scarce natural supply of 1 from the rare sponge source.

  14. Total synthesis of (+/-)-cytisine via the intramolecular heck cyclization of activated N-alkyl glutarimides.

    Science.gov (United States)

    Coe, J W

    2000-12-28

    [reaction:see text] A synthesis of racemic cytisine 1 has been developed utilizing an intramolecular Heck cyclization to prepare the bridged tricyclic intermediate 2. The cyclization employs activated glutarimide-derived ketene aminals 3 (X = P(O)OEt(2) or SO(2)CF(3)) and represents the first use of such intermediates in metal-catalyzed processes.

  15. Tissue distribution of total alkaloids in Strychni Semen vesicle gel in rats after transdermal administration%马钱子总碱囊泡凝胶经皮给药后在大鼠组织中的分布研究

    Institute of Scientific and Technical Information of China (English)

    李静雅; 苗凤茹; 朱丹; 林力; 林成仁; 刘建勋

    2012-01-01

    目的 研究马钱子总碱囊泡凝胶经皮给药后在大鼠组织中的分布.方法 18只SD大鼠经皮给予马钱子总碱囊泡凝胶后0.5、2、6h,采集大鼠皮肤、骨骼肌、脑、心、肺、肝、脾、肾、胃、小肠、脂肪、睾丸、子宫、关节等组织,以溶剂萃取法对样品进行提取,应用LC-MS/MS联用技术对各组织中的马钱子碱和士的宁进行测定.结果 经皮给药后,马钱子碱和士的宁在大鼠体内分布较广,主要分布在肺、肝、肾、小肠,其次为心脏、关节、皮肤等,而在脑、肌肉、脂肪中的分布量较低.结论 马钱子总碱囊泡凝胶能减少马钱子碱和士的宁在脑、心脏的分布,有利于降低中枢毒性和心脏毒性.%Objective To study the tissue distribution of total alkaloids in Strychni Semen vesicle gel after transdermal administration in rats. Methods Total alkaloids in Strychni Semen vesicle gel was applied to 18 SD rats of SPF grade. Tissues of skin, skeletal muscle, brain, heart, lung, liver, spleen, kidney, stomach, intestine, fat, testicle, uterus, and joint were collected at 0.5, 2, and 6 h after transdermal administration. Samples were extracted by ethyl acetate-n-butanol (7 : 3) and brucine and strychnine in each tissue were determined by LC-MS/MS method. Results The two ingredients were mainly distributed in lung, liver, kidney, and intestine, followed with heart, joint, and skin, while low in brain, musle, and fat. Conclusion Total alkaloids in Strychni Semen vesicle gel could reduce the distribution of brucine and strychnine in brain and heart, which is benefit to lower the toxicity of the two ingredients in central nervous system and cardiovascular system.

  16. Pyrrolizidine alkaloids from Heliotropium indicum

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Joao Sammy N.; Machado, Luciana L.; Pessoa, Otilia D.L.; Lemos, Telma L.G. [Ceara Univ., Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica]. E-mail: tlemos@dqoi.ufc.br; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacases, RJ (Brazil). Setor de Quimica de Produtos Naturais; Overk, Cassia R.; Ping Yao; Cordell, Geoffrey A. [University of Illinois at Chicago, IL (United States). College of Pharmacy. Dept. of Medicinal Chemistry and Pharmacognosy

    2005-11-15

    ndicine (1), a new pyrrolizidine alkaloid with unusual structural features, together with the known lycopsamine (2), were isolated from the roots of Heliotropium indicum (Boraginaceae). The structures were established by a combination of 1D and 2D NMR methods (COSY, HMQC, HMBC, and NOESY) and HREIMS. This is the first report of a lactone pyrrolizidine alkaloid in the genus Heliotropium. Compounds 1 and 2 were assayed for antioxidant activity and showed moderate activity. (author)

  17. 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... to their wide applications in medicinal chemistry, drug discovery and agrochemicals, the syntheses and isolation of BIMs have attracted attention of several chemists over last few years. Due to their symmetric structure, they are easy to synthesize...

  18. 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.

  19. Extraction and enrichment of total alkaloids of Plumula Nelumbinis by ultrahigh pressure-assisted micellar extraction combined with cloud-point extraction%超高压辅助浊点萃取法提取富集莲子心总生物碱

    Institute of Scientific and Technical Information of China (English)

    朱荣华; 王晓; 刘建华; 张树芹; 刘峰

    2013-01-01

    We determined the technical conditions of ultrahigh pressure-assisted micellar extraction by such singleelement experiment as surface active agent type,concentration,extraction pressure,time and the ratio of solid and liquid to construct the extraction and enrichment process of total alkaloids of Plumula Nelumbinis.We implemented the enrichment of the alkaloids of Plumula nelumbinis by NaCl addition,cloud point extraction and double water phase separation.The optimal extraction conditions are 5% (w/w) OP-10 solvent,extraction pressure of 100 MPa,extraction time of 1 min and solid/liquid ratio of 1∶20 (g/mL).The optimal extraction yield of total alkaloids is 103.6 mg/g.Its recovery rate is 70.73% and the pre-concentration factor (CF) is 8.6 under the conditions of 15% NaCl addition,stability of 10 min at 50 ℃ and two-phase separation.Results show that the extraction process is rapid and benefit for environment.%通过表面活性剂类型、浓度、提取压力、时间、料液比等单因素实验确定了超高压辅助胶束提取的工艺条件,并通过加入NaCl和加热引发体系浊点,诱导双水相分离,实现了莲子心生物碱的富集.结果表明,最佳提取工艺为质量分数5%的OP-10为溶剂,提取压力100 MPa,提取时间1 min,料液比1:20 (g/mL),莲子心生物碱的提取率可达到103.6 mg/g.提取液中加入NaCl使其质量分数达到15%,在50℃条件下平衡10 min,两相分离,离心后莲子心生物碱的萃取回收率为70.73%,浓缩系数为8.6.此方法快速高效、环境友好.

  20. 钩藤总碱对高血压动脉压力感受反射和对高血压靶器官的作用∗%Effects of Total Alkaloids of Rhynchophylline on Baroreflex and Hypertensive Target Organs in Spontaneous Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    刘叶玲; 王中师; 张许

    2015-01-01

    目的:观察钩藤总碱对高血压靶器官的作用。方法自发性高血压模型大鼠40只,随机分为4组,正常对照组、天麻钩藤饮组、钩藤总碱小剂量组和钩藤总碱大剂量组,每组10只,分别口服普通饲料、天麻钩藤饮颗粒(750 mg•d-1)、钩藤总碱2.5,15.0 mg•d-1。采用改良的 Smyth 方法测定各组大鼠的动脉压力感受反射功能,20周后,取大鼠心、脑、肾,进行组织学观察。结果正常对照组、天麻钩藤饮组、钩藤总碱小剂量组和钩藤总碱大剂量组第16周动脉压力感受反射敏感性分别为(0.27±0.05),(0.31±0.06),(0.35±0.08),(0.34±0.08) ms•mmHg-1。正常对照组大鼠动脉压力感受反射功能降低,而其他各用药组没有降低;给药组大鼠可见心肌结构显著优于正常对照组,脑组织和肾小球结构未见显著改善。结论钩藤总碱对高血压靶器官心脏有保护作用。%Objective To investigate the effect of total alkaloids from Rhynchophylline on hypertensive target organs. Methods 40 spontaneous hypertensive rats (SHRs) were divided into 4 groups as follows: normal control group,positive control with Tianma Goutengyin granule at 750 mg•d-1 ,total alkaloids from Rhynchophylline at 2.5 mg•day-1 as low dosage,and at 15.0 mg•d-1 as high dosage.All the rats were fed up for 20 weeks,and baroreflex sensitivity (BRS,in ms•mmHg-1)was determined by revised Smyth’s method.Heart,brain and kidney of the rats were sectioned for histological analysis at the end of 20th week. Results In sixteenth weeks,BRS of positive control,Tianma Goutengyin granule group,total alkaloids at low dosage and high dosage were(0.27±0.05),(0.31±0.06),(0.35±0.08),(0.34±0.08) ms•mmHg-1,respectively.BRS in SHR was not decreased except in the positive control.The treatment groups were superior to the normal control group in structure of heart,but not in the brain and kidney of the rats. Conclusion Total alkaloids from

  1. The use of genomics and metabolomics methods to quantify fungal endosymbionts and alkaloids in grasses.

    Science.gov (United States)

    Rasmussen, Susanne; Lane, Geoffrey A; Mace, Wade; Parsons, Anthony J; Fraser, Karl; Xue, Hong

    2012-01-01

    The association of plants with endosymbiotic micro-organisms poses a particular challenge to metabolomics studies. The presence of endosymbionts can alter metabolic profiles of plant tissues by introducing non-plant metabolites such as fungal specific alkaloids, and by metabolic interactions between the two organisms. An accurate quantification of the endosymbiont and its metabolites is therefore critical for studies of interactions between the two symbionts and the environment.Here, we describe methods that allow the quantification of the ryegrass Neotyphodium lolii fungal endosymbiont and major alkaloids in its host plant Lolium perenne. Fungal concentrations were quantified in total genomic DNA (gDNA) isolated from infected plant tissues by quantitative PCR (qPCR) using primers specific for chitinase A from N. lolii. To quantify the fungal alkaloids, we describe LC-MS based methods which provide coverage of a wide range of alkaloids of the indolediterpene and ergot alkaloid classes, together with peramine.

  2. Total Syntheses of (+)-Grandilodine C and (+)-Lapidilectine B and Determination of their Absolute Stereochemistry.

    Science.gov (United States)

    Nakajima, Masaya; Arai, Shigeru; Nishida, Atsushi

    2016-03-01

    Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.

  3. A practical total synthesis of the microbial alkaline proteinase inhibitor (MAPI).

    Science.gov (United States)

    Haebich, Dieter; Hillisch, Alexander; El Sheikh, Sherif

    2009-12-01

    Diverse serine and cysteine proteases as well as alkaline proteinases and elastases play a crucial role in numerous biological processes. Natural peptide aldehydes such as the "microbial alkaline proteinase inhibitor" (MAPI, 1) are valuable tools to characterize novel enzymes and to study their function in nature. Within a drug discovery program we wanted to design and explore non-natural MAPI congeners with novel biological profiles. To that end we devised a simple, practical, and scalable synthesis of MAPI 1 from readily available amino acid building blocks. The modular nature of our approach allows convenient structural modification of the MAPI backbone.

  4. The discovery of potent antitumor agent C11-deoxypsymberin/irciniastatin A: total synthesis and biology of advanced psymberin analogs.

    Science.gov (United States)

    Huang, Xianhai; Shao, Ning; Huryk, Robert; Palani, Anandan; Aslanian, Robert; Seidel-Dugan, Cynthia

    2009-02-19

    Structure-activity relationship (SAR) studies by modification of the unsaturated side chain of potent anticancer marine natural product psymberin/irciniastatin A (1) suggest that substitution at C4 and C5 is important for the cytotoxicity of psymberin, but the terminal double bond is not essential for activity. An aryl group is a good replacement for the olefin. The total synthesis of structurally simplified C11-deoxypsymberin (29) was completed, and its activity is consistently more potent than the natural product which provides a unique opportunity for further SAR studies in the psymberin and pederin family. Preliminary mechanism studies suggest the mode of action of psymberin is through cell apoptosis.

  5. Tanjungides A and B: new antitumoral bromoindole derived compounds from Diazona cf formosa. isolation and total synthesis.

    Science.gov (United States)

    Murcia, Carmen; Coello, Laura; Fernández, Rogelio; Martín, María Jesús; Reyes, Fernando; Francesch, Andrés; Munt, Simon; Cuevas, Carmen

    2014-02-21

    Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey's analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines.

  6. A novel cis-selective cyclohexanone annulation as the key step of a total synthesis of the sesquiterpene isoacanthodoral.

    Science.gov (United States)

    Hampel, Thomas; Brückner, Reinhard

    2009-11-05

    Isoacanthodoral (1) is a structurally unique sesquiterpene in that it is a bicyclo[4.4.0]dec-1-ene with a cis- rather than the common trans-junction between the constituting rings. An efficient construction of this motif has been accomplished by a novel cis-selective cyclohexanone annulation, combining the lithium enolate of ester 8, the alpha,beta-unsaturated ester 6, and vinylmagnesium bromide in a single synthetic operation. For completing the total synthesis of 1, a Shapiro-olefination/hydrogenation sequence and a reductive cyanation were employed.

  7. Total synthesis of feglymycin based on a linear/convergent hybrid approach using micro-flow amide bond formation

    Science.gov (United States)

    Fuse, Shinichiro; Mifune, Yuto; Nakamura, Hiroyuki; Tanaka, Hiroshi

    2016-11-01

    Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we describe the total synthesis of feglymycin based on a linear/convergent hybrid approach. Our originally developed micro-flow amide bond formation enabled highly racemizable peptide chain elongation based on a linear approach that was previously considered impossible. Our developed approach will enable the practical preparation of biologically active oligopeptides that contain highly racemizable amino acids, which are attractive drug candidates.

  8. Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis

    Science.gov (United States)

    Murcia, Carmen; Coello, Laura; Fernández, Rogelio; Martín, María Jesús; Reyes, Fernando; Francesch, Andrés; Munt, Simon; Cuevas, Carmen

    2014-01-01

    Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines. PMID:24566261

  9. Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis

    Directory of Open Access Journals (Sweden)

    Carmen Murcia

    2014-02-01

    Full Text Available Tanjungides A (1 (Z isomer and B (2 (E isomer, two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines.

  10. The first protein ever synthesized in vitro——a personal reminiscence of the total synthesis of crystalline insulin

    Institute of Scientific and Technical Information of China (English)

    ZHANG YouShang

    2010-01-01

    @@ The total synthesis of crystalline bovine insulin started in 1958 was fully accomplished in 1965.This formidable task was a collaboration of the Institute of Biochemistry in Shanghai, the Institute of Organic Chemistry in Shanghai and the Department of Chemistry in Beijing University.It is difficult to say exactly how many people were involved in this project, as many contributors, e.g.Director Wang YingLai and Deputy Director Cao TianQin of the Institute of Biochemistry, were not included in the author list of the published papers.

  11. Optimization of Extraction Process of Scutellaria barbata Total Alkaloids with Central-Composite-Design Response-Surface Method%星点设计-效应面法优化半枝莲总生物碱提取工艺

    Institute of Scientific and Technical Information of China (English)

    刘欣; 杨新; 张丽; 方振峰; 张涛

    2016-01-01

    Objective To optimize the extraction process of Scutellariabar bata total alkaloids with central-composite-design response-surface method. Methods Five main factors including ethanol volume fraction ,extraction time ,solid-liquid ratio ,extraction temperature ,and extraction times on this reflux extraction process were investigated ,to screen the influence of various factors on the yield of S. barbata total alkaloid extraction with ultraviolet spectrophotometry. Central composite design was used to design experiments ,and SAS was used to establish a prediction model ,and response surface method was used to abtain the best extraction process. Results The optimal process conditions were 40. 06 times of 55. 20%ethanol reflux extraction under 85℃for two times ,each 113. 29 min. Under the optimal process conditions , the total alkaloid content was 26. 932 9 mg/g , and the deviation of predicted values and measured values were less than 2%. The binomial fitting correlation coefficient was R2=0. 997 5. Conclusion Central-composite-design response-surface methods is successfully used for the optimization on theextraction process of S. barbatatotal alkaloids , with good predictability and stability.%目的:采用星点设计-效应面法优化半枝莲总生物碱回流提取工艺。方法采用紫外分光光度法检测半枝莲总生物碱含量,对乙醇浓度、提取时间、固液比、提取温度、提取次数5个因素进行考察,确定对半枝莲总生物碱提取量影响最大的因素并确定其取值范围,在此基础上进行星点设计实验,SAS软件建立预测模型,采用效应面法优化最佳提取条件。结果确定最优提取工艺条件为温度85℃,40.06倍量55.20%乙醇回流提取2次,每次113.29 min。最佳工艺条件下,测得总生物碱提取量为26.9329 mg/g,实测值与预测值偏差小于2%,二项式拟合的相关系数R2=0.9975。结论采用星点设计-效应面法优化半枝莲总生物碱

  12. Modular and Stereodivergent Approach to Unbranched 1,5,9,n-Polyenes: Total Synthesis of Chatenaytrienin-4.

    Science.gov (United States)

    Adrian, Juliane; Stark, Christian B W

    2016-09-16

    An iterative strategy for the stereodivergent synthesis of unbranched 1,5,9,n-polyenes (and -polyynes) was investigated. Starting from a terminal alkyne the iteration cycle consists of a C3 extension (allylation), a chemoselective hydroboration, an alkyne reduction, and an oxidation of the associated alcohol with subsequent C1 homologation. Double bond geometry is controlled using stereoselective alkyne reductions, employing either the Lindlar hydrogenation protocol or an aluminum hydride reduction. In a model sequence it was demonstrated that the strategy is applicable to the synthesis of 1,5,9,n-polyenes with any possible double bond configuration accessible in equally high efficiency and selectivity. It is worth noting that our approach does not require any protecting group chemistry. Furthermore, using the same strategy, the first total synthesis of chatenaytrienin-4, the proposed unsaturated biosynthetic precursor of the bis-THF acetogenin membranacin, was examined. Thus, the all-cis 1,5,9-triene natural product was prepared in 15 steps from commercially available starting materials in 6% overall yield.

  13. 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.

  14. The Chemistry of the Akuammiline Alkaloids.

    Science.gov (United States)

    Adams, Gregory L; Smith, Amos B

    2016-01-01

    An update on the literature covering the akuammiline family of alkaloids is presented. This chapter begins with a summary of new akuammiline alkaloids reported since 2000 and is followed by an overview of new reported bioactivities of akuammiline alkaloids since 2000. The remainder of the chapter comprises a comprehensive review of the synthetic chemistry that has been reported in the last 50 years concerning akuammiline alkaloids and their structural motifs.

  15. Total synthesis and stereochemical confirmation of manassantin A, B, and B1.

    Science.gov (United States)

    Hanessian, Stephen; Reddy, Gone Jayapal; Chahal, Navjot

    2006-11-23

    Stereocontrolled total syntheses of manassantins A, B, and B1 and saucerneol are described for the first time based on a novel cycloetherification of end-differentiated benzylic alcohols as a common intermediate. [structure: see text].

  16. The First Total Synthesis of 4,4′-Biisofraxidin

    Institute of Scientific and Technical Information of China (English)

    LEi,Jiang-Guang(雷建光); LIN,Gu-Qiang(林国强)

    2002-01-01

    The 4,4′- biisofraxidin, isolated from balsamina L. was synthesized for the first time in the total yield of 7% by 11 steps, in which the key step was the cyclization and Ni(0)- catalyzed coupling reaction.

  17. 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.

  18. Alkaloids from Stems of Ervatamia yunnanensis (Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    Shuang LIANG; Xin Gen LUO; Hai Sheng CHEN; Xiao Dong ZHANG; Mao HUANG; Wen Yong LIU

    2006-01-01

    Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis. Among them, 10-hydroxy-19, 20-dihydroisositsirikine (Ⅰ) is new. The other five are known alkaloids,namely: matrine (Ⅱ), 19, 20-dihydroisositsuikine (Ⅲ), 19-s-voacangarine (Ⅳ), 11'-methoxyl- 19s-heyneanine (Ⅴ), conodurine (Ⅵ). The structural elucidation of the alkaloids was based on spectral means.

  19. Alkaloids from stems of Ervatamia yunnanensis

    Institute of Scientific and Technical Information of China (English)

    Xin Gen Luo; Hai Sheng Chen; Shuang Liang; Mao Huang; Wei Dong Xuan; Li Jin

    2007-01-01

    Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis.Among them, yunnanensine (Ⅰ) is new.The other five are known alkaloids, namely: 19,20-E-vallesamine (Ⅱ), 19s-heyneanine (Ⅲ), ibogaine (Ⅳ), ibogamine (Ⅴ), coronaridine (Ⅵ).The structural elucidation of the alkaloids was based on spectral means.

  20. 27 CFR 21.99 - Brucine alkaloid.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  1. Total synthesis and biochemical evaluation of azumamides A–E and analogs

    DEFF Research Database (Denmark)

    Villadsen, Jesper

    showed that the azumamides are poor inhibitors of class IIa HDACs, but potent inhibitors of HDAC1–3, 10, and 11 (IC50 values between 14 to 67 nM). Furthermore we showed that carboxylic acid containing compounds (azumamide C and E) were more potent than their carboxyamide counterparts (azumamide A and B...... azumamide C analog was developed in order to investigate the effect of the zinc-binding moiety. Preliminary testing showed that this compound was active against HDAC3 with an IC50 of 3 μM. The straight forward synthesis of the -amino acid required for this analog also illustrate the effectiveness......Histone deacetylases (HDAC) are a family of enzymes, which serve as epigenetic modulators. Their biological function has been related to DNA transcription and regulation of various biochemical pathways. Development of isoform selective HDAC inhibitors could be useful for dissecting the individual...

  2. 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.

  3. Total synthesis of marinomycin A using salicylate as a molecular switch to mediate dimerization

    Science.gov (United States)

    Evans, P. Andrew; Huang, Mu-Hua; Lawler, Michael J.; Maroto, Sergio

    2012-08-01

    Antibiotics play a significant role in human health because of their ability to treat life-threatening bacterial infections. The growing problems with antibiotic resistance have made the development of new antibiotics a World Health Organization priority. Marinomycin A is a member of a new class of bis-salicylate-containing polyene macrodiolides, which have potent antibiotic activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Herein, we describe a triply convergent synthesis of this agent using the salicylate as a novel molecular switch for the chemoselective construction of the macrodiolide. This strategy raises new questions regarding the biosynthetic role of the salicylate and its potential impact on the mechanism of action of these types of agents. For instance, in contrast to penicillin, which enhances the electrophilicity of the cyclic amide through ring strain, salicylates reduce the electrophilicity of the aryl ester through an intramolecular resonance-assisted hydrogen bond to provide an amide surrogate.

  4. 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.

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

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jixiang; GUO Jinsheng; OU Lailiang

    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.

  6. Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches

    Directory of Open Access Journals (Sweden)

    Man-Chin Chung

    2008-04-01

    Full Text Available We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4’’-nitrophenoxycarbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetylamino]-diphenylmethyl ester-5-dioxide (5, a new cephalosporinderivative. This compound can be used as the carrier of a wide range of drugs containingan amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylaminopentylcarbamate]-8-oxo-7-[(2-thienyloxoacetylamino]-diphenylmethyl ester-5-dioxide (6, as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylaminopentylcarbamate]-8-oxo-7-[(2-thienyloxoacetylamino]- 5-dioxide (7 are alsodescribed, together with their total 1H- and 13C-NMR assignments.

  7. 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

  8. Alkaloids with antioxidant activities from Aconitum handelianum.

    Science.gov (United States)

    Yin, Tian-Peng; Cai, Le; Xing, Yun; Yu, Jing; Li, Xue-Jiao; Mei, Rui-Feng; Ding, Zhong-Tao

    2016-06-01

    A new C20-diterpenoid alkaloid handelidine (1) and twenty-seven known alkaloids (2-28) were isolated from the roots of Aconitum handelianum. Their structures were established on the basis of extensive spectroscopic analyses. The study indicated that denudatine-type C20-diterpenoid alkaloids with vicinal-triol system and benzyltetrahydroisoquinoline alkaloids exhibited significant antioxidant activities measured by three antioxidant test systems. The aconitine-type C19-diterpenoid alkaloids could serve as potential secondary antioxidants for their strong binding effects to metal ions.

  9. GC-MS investigation of Amaryllidaceae alkaloids in Galanthus xvalentinei nothosubsp. subplicatus.

    Science.gov (United States)

    Sarikaya, Buket Bozkurt; Berkov, Strahil; Bastida, Jaume; Kaya, Gulen Irem; Onur, Mustafa Ali; Somer, Nehir Unver

    2013-03-01

    A GC-MS analysis of alkaloids in the aerial parts and bulbs of Galanthus xvalentinei nothosubsp. subplicatus was performed for the first time. Totally, twenty-six alkaloids were identified, of which tazettine and galanthindole were the major ones. Acetylcholinesterase inhibitory activity of the alkaloidal extracts was determined using modified in vitro Ellman's method. Significant anticholinesterase activity was observed in the tested samples (bulbs: IC50 = 21.3 microg/mL, aerial parts: IC50 = 16.3 microg/mL).

  10. Structural and quantitative analysis of Equisetum alkaloids.

    Science.gov (United States)

    Cramer, Luise; Ernst, Ludger; Lubienski, Marcus; Papke, Uli; Schiebel, Hans-Martin; Jerz, Gerold; Beuerle, Till

    2015-08-01

    Equisetum palustre L. is known for its toxicity for livestock. Several studies in the past addressed the isolation and identification of the responsible alkaloids. So far, palustrine (1) and N(5)-formylpalustrine (2) are known alkaloids of E. palustre. A HPLC-ESI-MS/MS method in combination with simple sample work-up was developed to identify and quantitate Equisetum alkaloids. Besides the two known alkaloids six related alkaloids were detected in different Equisetum samples. The structure of the alkaloid palustridiene (3) was derived by comprehensive 1D and 2D NMR experiments. N(5)-Acetylpalustrine (4) was also thoroughly characterized by NMR for the first time. The structure of N(5)-formylpalustridiene (5) is proposed based on mass spectrometry results. Twenty-two E. palustre samples were screened by a HPLC-ESI-MS/MS method after development of a simple sample work-up and in most cases the set of all eight alkaloids were detected in all parts of the plant. A high variability of the alkaloid content and distribution was found depending on plant organ, plant origin and season ranging from 88 to 597mg/kg dried weight. However, palustrine (1) and the alkaloid palustridiene (3) always represented the main alkaloids. For the first time, a comprehensive identification, quantitation and distribution of Equisetum alkaloids was achieved.

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

    OpenAIRE

    Heald, C. L.; Goldstein, A. H.; Allan, J. D.; Aiken, A. C.; Apel, E.; Atlas, E. L.; Baker, A. K; T. S. Bates; Beyersdorf, A. J.; Blake, D. R.; CAMPOS, T. de; Coe, H; Crounse, J. D.; P. F. DeCarlo; J. A. de Gouw

    2007-01-01

    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 ...

  12. Palladium-catalyzed asymmetric allylic substitution of 2-arylcyclohexenol derivatives: asymmetric total syntheses of (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine.

    Science.gov (United States)

    Nishimata, Toyoki; Sato, Yoshihiro; Mori, Miwako

    2004-03-19

    Much interest has been shown in Amaryllidaceae alkaloids as synthetic targets due to their wide range of biological activities. Over 100 alkaloids have been isolated from members of the Amaryllidaceae family; most of them can be classified into eight skeletally homogeneous groups. We have succeeded in the first asymmetric total syntheses of the crinane-type alkaloids (+)-crinamine (1), (-)-haemanthidine (2), and (+)-pretazettine (3). The starting cyclohexenylamine 14 was obtained from allyl phosphonate 11c by palladium-catalyzed asymmetric amination in 82% yield and with 74% ee. The product was recrystallized from MeOH. Interestingly, (-)-14 with 99% ee was obtained from the mother liquor (74% recovery). Intramolecular carbonyl-ene reaction of (-)-10 proceeds in a highly stereoselective manner to give hexahydroindole derivative 9 as the sole product. In the Lewis-acid-catalyzed carbonyl-ene reaction, an interesting rearrangement product, 20, was isolated in high yield. From 9, (+)-crinamine was synthesized. Thus, the asymmetric total synthesis of (+)-crinamine was achieved in 10 steps from 11c, and the overall yield is 19%. The total synthesis of (-)-haemanthidine was also achieved from 9 by a short sequence of steps.

  13. 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.

  14. Tandem Mass Spectrometry for Structural Identification of Sesquiterpene Alkaloids from the Stems of Dendrobium nobile Using LC-QToF.

    Science.gov (United States)

    Wang, Yan-Hong; Avula, Bharathi; Abe, Naohito; Wei, Feng; Wang, Mei; Ma, Shuang-Cheng; Ali, Zulfiqar; Elsohly, Mahmoud A; Khan, Ikhlas A

    2016-05-01

    Dendrobium nobile is one of the fundamental herbs in traditional Chinese medicine. Sesquiterpene alkaloids are the main active components in this plant. Due to weak ultraviolet absorption and low content in D. nobile, these sesquiterpene alkaloids have not been extensively studied using chromatographic methods. Herein, tandem mass spectrometry combined with liquid chromatography separation provides a tool for the identification and characterization of the alkaloids from D. nobile. A total of nine sesquiterpene alkaloids were characterized by ultrahigh-performance liquid chromatography tandem mass spectrometry. These alkaloids can be classified into two subgroups that are represented by dendrobine and nobilonine. Tandem mass spectrometric studies revealed the fragmentation pathways of these two subgroup alkaloids that were used for the identification and characterization of other alkaloids in D. nobile. Characterization of these alkaloids using accurate mass and diagnostic fragments provided a reliable methodology for the analysis of D. nobile by ultrahigh-performance liquid chromatography tandem mass spectrometry. The limit of detection was defined as the signal-to-noise ratio equal to 3 : 1. Limits of detection of dendrobine and nobilonine were less than 30 ng/mL. The developed method was applied for the analysis of various Dendrobium species and related dietary supplements. Alkaloids were identified from D. nobile, but not detected from commercial samples including 13 other Dendrobium species and the 7 dietary supplements.

  15. Effect of certain elicitors on production of pyrrolizidine alkaloids in hairy root cultures of Echium rauwolfii.

    Science.gov (United States)

    Abd El-Mawla, A M A

    2010-03-01

    Hairy root cultures of Echium rauwolfii were obtained by infection of sterile apical shoots with Agrobacterium rhizogenes. The linear increase in fresh weight was found to be parallel to the alkaloids production. The transformed cultures were exposed to different elicitors, such as methyl jasmonate (MJ), quercetin and salicylic acid in order to increase their productivity. Pyrrolizidine alkaloids were quantitatively determined by HPLC. Estimation of total alkaloids was achieved by peak area calculations. MJ at a concentration of 100 microM induced the accumulation of total alkaloids about 19-fold compared to the untreated control. The flavonoid quercetin (Q) at a concentration of 50 microM enhanced the pyrrolizidine accumulation approximately 6-fold. The induction effect of both MJ and Q can be suppressed by pre-incubation of hairy root cultures with salicylic acid.

  16. 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.

  17. 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)

  18. Mechanistic studies on gold mediated cross-coupling reactions and total synthesis of (_+ )-epiglobulol

    OpenAIRE

    Livendahl, Madeleine

    2013-01-01

    Tras la activación con complejos catiónicos de oro(I), los 1,6-eninos conteniendo alcoholes o éteres se pueden atrapar intra- o intermolecularmente con alquenos o éteres bencílicos. Esta reacción estereospecífica da lugar a compuestos tricíclicos relacionados con los sesquiterpenos 4-epiglobulol y 4-aromadendreno. La síntesis racémica del 4-epiglobulol se comenzó a partir del geranyl acetona que es comercial. Hemos cumplido la síntesis total del producto natural (±)-epiglobulol en 5 pasos c...

  19. 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)

  20. 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.

  1. Extending the Glucosyl Ceramide Cassette Approach: Application in the Total Synthesis of Ganglioside GalNAc-GM1b

    Directory of Open Access Journals (Sweden)

    Miku Konishi

    2013-12-01

    Full Text Available The development of a novel cyclic glucosyl ceramide cassette acceptor for efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB groups were selected as protecting groups at C2 and C3 of the glucose residue with the aim of improving the functionality of the cassette acceptor. The choice of the PMB group resulted in a loss of β-selectivity, which was corrected by using an appropriate tether to control the spatial arrangement and the nitrile solvent effect. To investigate the effect of linker structure on the β-selectivity of intramolecular glycosylation, several linkers for tethering the glucose and ceramide moiety were designed and prepared, namely, succinyl, glutaryl, dimethylmalonyl, and phthaloyl esters. The succinyl ester linker was the best for accessing the cassette form. The newly designed glucosyl ceramide cassette acceptor was then applied in the total synthesis of ganglioside GalNAc-GM1b.

  2. 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.

  3. 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

    2015-07-22

    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.

  4. Preparative isolation of guaipyridine sesquiterpene alkaloid from Artemisia rupestris L. flowers using high-speed counter-current chromatography.

    Science.gov (United States)

    Su, Zhen; Wu, Hankui; Yang, Yi; Aisa, Haji Akber; Slukhan, Usmanova; Aripova, Salimakhon

    2008-07-01

    Although the medicinal plant Artemisia rupestris L. has been widely researched for several decades, its alkaloids have never been isolated before. To our surprise, the alkaloids in the plant were not detected in the stems but detected in the flowers. Herein, a novel and strange guaipyridine sesquiterpene alkaloid with a carboxyl group named rupestine was purified successfully from the total alkaloids extracted from the flowers by high-speed counter-current chromatography (HSCCC). The two-phase solvent system used was composed of ethyl acetate-methanol-water (8:1:7, v/v/v). Fifty six milligrams of rupestine was obtained at over 97% purity and 95% recovery from 200 mg of the total alkaloids in one-step separation. Its structure was elucidated by spectroscopic methods including high resolution ESI-MS, (1)H NMR, (13)C NMR, Heteronuclear Multiple Bond Correlation (HMBC), Heteronuclear Single Quantum Coherence (HSQC), and Nuclear Overhauser Enhancement Spectroscopy (NOESY).

  5. Pro-toxic dehydropyrrolizidine alkaloids in the traditional Andean herbal medicine “asmachilca”

    Science.gov (United States)

    Colegate, Steven M.; Boppré, Michael; Monzón, Julio; Betz, Joseph M.

    2015-01-01

    Ethnopharmacological relevance Asmachilca is a Peruvian medicinal herb preparation ostensibly derived from Eupatorium gayanum Wedd. = Aristeguietia gayana (Wedd.) R.M. King & H. Rob. (Asteraceae: Eupatorieae). Decoctions of the plant have a reported bronchodilation effect that is purported to be useful in the treatment of respiratory allergies, common cold and bronchial asthma. However, its attractiveness to pyrrolizidine alkaloid-pharmacophagous insects indicated a potential for toxicity for human consumers. Aim of the study To determine if commercial asmachilca samples, including fully processed herbal teas, contain potentially toxic 1,2-dehydropyrrolizidine alkaloids. Materials and methods Two brands of “Asmachilca” herbal tea bags and four other commercial samples of botanical materials for preparing asmachilca medicine were extracted and analyzed using HPLC-esi(+)MS and MS/MS for the characteristic retention times and mass spectra of known dehydropyrrolizidine alkaloids. Other suspected dehydropyrrolizidine alkaloids were tentatively identified based on MS/MS profiles and high resolution molecular weight determinations. Further structure elucidation of isolated alkaloids was based on 1D and 2D NMR spectroscopy. Results Asmachilca attracted many species of moths which are known to pharmacophagously gather dehydropyrrolizidine alkaloids. Analysis of 5 of the asmachilca samples revealed the major presence of the dehydropyrrolizidine alkaloid monoesters rinderine and supinine, and their N-oxides. The 6th sample was very similar but did not contain supinine or its N-oxide. Small quantities of other dehydropyrrolizidine alkaloid monoesters, including echinatine and intermedine, were also detected. In addition, two major metabolites, previously undescribed, were isolated and identified as dehydropyrrolizidine alkaloid monoesters with two “head-to-tail” linked viridifloric and/or trachelanthic acids. Estimates of total pyrrolizidine alkaloid and N

  6. Chamobtusin A, a novel skeleton diterpenoid alkaloid from Chamaecyparis obtusa cv. tetragon.

    Science.gov (United States)

    Zhang, Yu-Mei; Tan, Ning-Hua; Lu, Yang; Chang, Ying; Jia, Rui-Rui

    2007-10-25

    The novel diterpenoid alkaloid chamobtusin A (1) was isolated from the branches and leaves of Chamaecyparis obtusa cv. tetragon. Its structure and relative stereochemistry were mainly determined by MS, 2D NMR, and X-ray methods. The methanol extracts, total alkaloids of C. obtusa cv. tetragon, and chamobtusin A were tested for their cytotoxicities against A549 and K562 human tumor cell lines.

  7. 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.

  8. 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

  9. 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.

  10. Alcalóides alquilpiridínicos de esponjas marinhas Alkylpyridine alkaloids from marine sponges

    Directory of Open Access Journals (Sweden)

    Adaíla M. P. Almeida

    1997-04-01

    Full Text Available The chemistry of alkylpyridine alkaloids originating from marine sponges is comprehensively reviewed, with emphasis on their natural occurrence, methods for their isolation, spectroscopic characterization, biological activities e chemical synthesis. A likely chemotaxonomic role is suggested, as markers for sponges of the Order Haplosclerida (Demospongiae.

  11. Effects of total alkaloids of Tripterygium hypoglaucum Hutch on proliferation and apoptosis of human colon cancer cell line HCT116%昆明山海棠总生物碱对人结肠癌HCT116细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    黄晓春; 刘晋档; 周燕虹; 敖琳; 杨录军; 曹佳

    2009-01-01

    目的 研究昆明山海棠总生物碱(total alkaloids of tripterygium hypoglaucum hutch,THHta)对人结肠癌HCT116细胞增殖及凋亡的影响.方法 采用MTT法检测THHta对HCT116细胞增殖的抑制作用;用倒置及荧光显微镜观察THHta作用后HCT116细胞形态的变化;流式细胞术检测THHta对HCT116细胞周期及凋亡的影响,Western bolt检测凋亡相关caspase-3及PARP蛋白表达.结果 THHLa能显著抑制HCT116细胞增殖,抑制率与剂量和时间呈依赖关系.THHta作用HCT116细胞48、72 h的IC_(50)值小于20 μg/ml.THHta(10μg/ml)能诱导HCT116细胞G_0/G_1期比例增加及细胞凋亡,caspase-3活化及PARP蛋白剪切显著增强.结论 THHta能显著抑制HCT116细胞增殖,并可诱导HCT116细胞G_0/G_1期阻滞及细胞凋亡.%Objective To investigate the effects of total alkaloids of tripterygium hypoglaucum hutch (THHta) on the proliferation and apoptosis of human colon cancer cell line HCT116.Methods The effects of THHta on the proliferation of HCT116 cells were assessed by MTT assay. Morphological changes of HCT116cells were observed with invert microscopy and fluorescence microscopy. The cell cycle distribution and apopto-sis of HCT116 cells were examined by flow eytometry (FCM). The expression of active caspase-3 and cleaved PARP were detected by Western blot assay.Results THHta inhibited the proliferation of HCT116 cells in a concentration-and time-dependent manner. The IC_(50) values of THHta which affected HCT116 cells for 48 and 72 h were less than 20 μg/ml. THHta (10 μg/ml) increased the percentage of cells at the G_0/G_1 phase, in-duced the apoptosis of HCT116 cells, and increased the amount of active caspase-3 and cleaved PARP in HCT116 cells. Conclusion THHta inhibits proliferation, causes G_0/G_1 phase arrest and induces apoptosis in cer HCT116 cells in vitro.

  12. Identification and quantification of hepatotoxic pyrrolizidine alkaloids in the Ethiopian medicinal plant Solanecio gigas (Asteraceae).

    Science.gov (United States)

    Asres, K; Sporer, F; Wink, M

    2007-09-01

    The pyrrolizidine alkaloid content of Solanecio gigas (Vatke) C. Jeffrey (Asteraceae), an Ethiopian medicinal plant widely used for the treatment of colic, diarrhea, gout, otitis media, typhoid fever, and noted for its wound dressing and antiabortifacient activities was studied. The flower and leaf extracts contained 0.19% and 0.14% alkaloids (dry weight), respectively. GLC-MS analysis indicated that all the alkaloids in the flowers are pyrrolizidine alkaloids (PAs), whereas the leaves contain other type of alkaloids with PAs occurring in low concentrations. Roughly, 80% and 90% of the total PAs in the flowers and the leaves, respectively, were shown to occur as N-oxides. Eighteen alkaloids were detected in the flower extract with the retronecine type twelve-membered macrocyclic diesters integerrimine, senecionine and usaramine comprising 82% of the total PA content. Analysis of the PA profile of the leaves indicated that it has a simpler pattern than the one observed for the flowers. Only five PAs were detected in the leaves with integerrimine making up about 50% of the total PAs. Quantification of the PA content by GLC showed that the flowers and leaves contain 3321.21 and 84.84 microg per 10 g of dried plant material, respectively. These results indicate that users of this herb are at high risk of poisoning since the most toxic twelve membered macrocyclics of the retronecine type are the dominant PAs in the plant.

  13. Research synthesis of recommended acetabular cup orientations for total hip arthroplasty.

    Science.gov (United States)

    Harrison, Claire L; Thomson, Avril I; Cutts, Steven; Rowe, Philip J; Riches, Philip E

    2014-02-01

    Total hip arthroplasty (THA) is regarded as one of the most successful surgical procedures of modern times yet continues to be associated with a small but significant complication rate. Many early failures may be associated with poor component positioning with, in particular, acetabular component orientation dependent on the subjective judgement of the surgeon. In this paper, we compare the manufacturers' instructions on acetabular cup orientation with the literature-based recommended safety zones and surgical technique, by transforming them onto a single, clinically-relevant framework in which the different reference systems, safety guidelines and current instrumentation surgical techniques can be evaluated. The observed limited consensus between results reflects ongoing uncertainty regarding the optimum acetabular component positioning. As malpositioning of the acetabular cup increases the risk of revision surgery, any ambiguity over the correct position can have a causal effect. Our analysis highlights the need for a surgical reference system which can be used to describe the position of the acetabular cup intra-operatively.

  14. Sensitive determination of pyrrolizidine alkaloids in Tussilago farfara L. by field-amplified, sample-stacking, sweeping micellar electrokinetic chromatography.

    Science.gov (United States)

    Cao, Kun; Xu, Yi; Mu, Xiuni; Zhang, Qing; Wang, Renjie; Lv, Junjiang

    2016-11-01

    Pyrrolizidine alkaloids are the toxic components in Tussilago farfara L. Due to the lack of standard substances for quantitative analysis and traces of pyrrolizidine alkaloids in total alkaloids, the full quality control of Tussilago farfara L has been limited. In this study, we aimed to solve the difficulty of determination of pyrrolizidine alkaloids and identify more components in the total alkaloids. An on-line preconcentration method has been applied to improve determining sensitivity of pyrrolizidine alkaloids in Tussilago farfara L. in which included field-amplified sample stacking and sweeping in micellar electrokinetic capillary chromatography. The main parameters that affected separation and stacking efficiency were investigated in details. Under the optimal conditions, the sensitivity enhancement factors obtained by the developed method for the analytes were from 15- to 12-fold, the limits of detection of senkirkine and senecionine were 2∼5 μg/L. Senkirkine and senecionine have been detected in alkaloids (c) of Tussilago farfara L, along ferulic acid methyl ester and methyl caffeate. The developed method was also applied to the analysis of acid extraction (a) of Tussilago farfara L, and senkirkine could be detected directly. The results indicated that the developed method is feasible for the analysis of pyrrolizidine alkaloids in Tussilago farfara L with good recoveries.

  15. (+)-生物素全合成研究新进展%Recent Progresses in Total Synthesis of (+)-Biotin

    Institute of Scientific and Technical Information of China (English)

    钟铮; 武雪芬; 陈芬儿

    2012-01-01

    (+)-生物素是维生素B家族中的一员,自发现以来对其全合成的报道层出不穷.在最近十几年中,数十条新的合成路线和改进方法陆续报道.(+)-生物素全合成策略主要分为两类:对映选择性合成和立体专一性合成.前一策略中,通过各种反应方法对经典的Hoffmann-La-Roche-硫内酯法进行改进和完善,其中不对称催化合成的方法已成功应用于工业化生产;在后一策略中,以L-半胱氨酸为起始原料的合成途径得到了较大发展,正越来越具有工业意义.%(+)-Biotin is one of the B vitamins. The study on total synthesis of (+)-biotin is an incessant pursuit since it was discovered half century ago. During the past ten years great advances in this field have been made. The synthetic approaches toward the target molecule can be classified into two series: the enatioselective syntheses and the stereospecific syntheses. In former approach, modification of the already existed Hoffmann-La-Roche's lactone-thiolactone approach was further developed in diversified ways, especially the great advance in asymmetric synthesis of the chiral framework of (+)-biotin, which had been put into industrial practice successfully; in terms of the latter approach, i-cysteine or cystine can be regarded as more logical starting materials. Enriched by a plenty of ingenious novel strategies and tactics, this approach evolved more facile and practical than before.

  16. Total syntheses of the phytotoxic lactones herbarumin I and II and a synthesis-based solution of the pinolidoxin puzzle.

    Science.gov (United States)

    Fürstner, Alois; Radkowski, Karin; Wirtz, Conny; Goddard, Richard; Lehmann, Christian W; Mynott, Richard

    2002-06-19

    A concise approach to a family of potent herbicidal 10-membered lactones is described on the basis of ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. This includes the first total syntheses of herbarumin I (1) and II (2) as well as the synthesis of several possible macrolides of the pinolidoxin series. A comparison of their spectral and analytical data with those of the natural product allowed us to establish the stereostructure of pinolidoxin, a potent inhibitor of induced phenylalanine ammonia lyase (PAL) activity, as shown in 46. This finding, however, makes clear that a previous study dealing with the relative and absolute stereochemistry of this phytotoxic agent cannot be correct. An important aspect from the preparative point of view is the fact that the stereochemical outcome of the RCM reaction can be controlled by the choice of the catalyst. Thus, use of the ruthenium indenylidene complex 16 always leads to the corresponding (E)-alkenes, whereas the second generation catalyst 17 bearing an N-heterocyclic carbene ligand affords the isomeric (Z)-olefin with good selectivity. This course is deemed to reflect kinetic versus thermodynamic control of the cyclization reaction and therefore has potentially broader ramifications for the synthesis of medium-sized rings in general. A further noteworthy design feature is the fact that D-ribose is used as a convenient starting material for the preparation of both enantiomers of the key building block 14 by means of a "head-to-tail" interconversion strategy.

  17. Phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona bark (Rubiaceae: Cinchona calisaya)

    DEFF Research Database (Denmark)

    Maldonado Goyzueta, Carla Brenda; Barnes, Christopher James; Cornett, Claus

    2017-01-01

    against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from...... twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species...... of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation...

  18. 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.

  19. 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)

  20. 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.

  1. Pyrrolizidine alkaloids of senecio sp from Peru

    OpenAIRE

    2011-01-01

    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. lycopers...

  2. Four new fluorenone alkaloids and one new dihydroazafluoranthene alkaloid from Caulophyllum robustum Maxim.

    Science.gov (United States)

    Wang, Xiao-Ling; Liu, Bing-Rui; Chen, Chien-Kuang; Wang, Jun-Ru; Lee, Shoei-Sheng

    2011-09-01

    Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 μM.

  3. Pyrrolizidine alkaloids from Onosma erecta.

    Science.gov (United States)

    Damianakos, Harilaos; Sotiroudis, Georgios; Chinou, Ioanna

    2013-10-25

    The MeOH extract of the aerial parts of Onosma erecta afforded four new pyrrolizidine alkaloids, 7-O-acetylechinatine N-oxide (1), a viridinatine N-oxide stereoisomer (2), 7-epi-echimiplatine N-oxide (3), and onosmerectine N-oxide (4), and two additional new natural products, the acid 2,3-dimethyl-2,3,4-trihydroxypentanoic acid (5) and the acyloin 4-methyl-2-hydroxypentanone (6).

  4. Alkaloids produced by endophytic fungi: a review.

    Science.gov (United States)

    Zhang, Yanyan; Han, Ting; Ming, Qianliang; Wu, Lingshang; Rahman, Khalid; Qin, Luping

    2012-07-01

    In recent years, a number of alkaloids have been discovered from endophytic fungi in plants, which exhibited excellent biological properties such as antimicrobial, insecticidal, cytotoxic, and anticancer activities. This review mainly deals with the research progress on endophytic fungi for producing bioactive alkaloids such as quinoline and isoquinoline, amines and amides, indole derivatives, pyridines, and quinazolines. The biological activities and action mechanisms of these alkaloids from endophytic fungi are also introduced. Furthermore, the relationships between alkaloid-producing endophytes and their host plants, as well as their potential applications in the future are discussed.

  5. 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 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 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.

  6. A second-generation total synthesis of (+)-discodermolide: the development of a practical route using solely substrate-based stereocontrol.

    Science.gov (United States)

    Paterson, Ian; Delgado, Oscar; Florence, Gordon J; Lyothier, Isabelle; O'Brien, Matthew; Scott, Jeremy P; Sereinig, Natascha

    2005-01-01

    A novel total synthesis of the complex polyketide (+)-discodermolide, a promising anticancer agent of sponge origin, has been completed in 7.8% overall yield over 24 linear steps, with 35 steps altogether. This second-generation approach was designed to rely solely on substrate control for introduction of the required stereochemistry, eliminating the use of all chiral reagents or auxiliaries. The common 1,2-anti-2,3-syn stereotriad found in each of three subunits, aldehyde 9 (C(1)-C(5)), ester 40 (C(9)-C(16)), and aldehyde 13 (C(17)-C(24)), was established via a boron-mediated aldol reaction of ethyl ketone 15 and formaldehyde, followed by hydroxyl-directed reduction to give 1,3-diol 14. Alternatively, a surrogate aldehyde 22 was employed for formaldehyde in this aldol reaction, leading to the beta-hydroxy aldehyde 20 as a common building block, corresponding to the discodermolide stereotriad. Key fragment unions were achieved by a lithium-mediated anti aldol reaction of ester 40 and aldehyde 13 under Felkin-Anh control to provide (16S,17S)-adduct 51 and a boron-mediated aldol reaction between enone 10 and aldehyde 9, exploiting unprecedented remote 1,6-stereoinduction, to give the (5S)-adduct 57.

  7. Total synthesis of woodrosin I--part 1: preparation of the building blocks and evaluation of the glycosylation strategy.

    Science.gov (United States)

    Fürstner, Alois; Jeanjean, Fabien; Razon, Patrick; Wirtz, Conny; Mynott, Richard

    2003-01-03

    The preparation of three building blocks required for the total synthesis of woodrosin I (1) is outlined, a complex resin glycoside bearing a macrolide ring which spans four of the five sugars of its oligosaccharide backbone. Key steps involve the enantioselective, titanium-catalyzed addition of dipentylzinc to 5-hexenal, the glycosylation of the resulting alcohol 18 with the glucose-derived trichloroacetimidate 7, and further elaboration of the resulting product 19 into disaccharide 22 on treatment with the orthogonally protected glycosyl donor 15. The trichloroacetimidate method is also used for the formation of the second synthon represented by disaccharide 38. A model study shows that the assembly of the pentasaccharidic perimeter of 1 depends critically on the phasing of the glycosylation events between fragments 22, 38 and the rhamnosyl donor 27 due to the severe steric hindrance in the product. A particularly noteworthy finding is the fact that diol 22 can be regioselectively glycosylated at the 3'-OH group in high yield without protection of the neighboring 2'-OH function.

  8. Total synthesis of (R,R,R)- and (S,S,S)-schweinfurthin F: differences of bioactivity in the enantiomeric series.

    Science.gov (United States)

    Mente, Nolan R; Wiemer, Andrew J; Neighbors, Jeffrey D; Beutler, John A; Hohl, Raymond J; Wiemer, David F

    2007-02-15

    Total synthesis of the (R,R,R)- and (S,S,S)-enantiomers of the natural product schweinfurthin F has been completed. Comparisons of spectral data and optical rotations with those reported for the natural product, as well as a variety of bioassay data, allow assignment of the natural material as the (R,R,R)-isomer.

  9. Intraspecific variability in the alkaloid metabolism of Galanthus elwesii.

    Science.gov (United States)

    Berkov, Strahil; Sidjimova, Borjana; Evstatieva, Luba; Popov, Simeon

    2004-03-01

    Alkaloid pattern of individuals from 16 Bulgarian Galanthus elwesii populations was investigated by GC/MS and TLC. Twenty-one Amaryllidaceae alkaloids were detected and 14 of them were identified. Crinane type alkaloids, haemanthamine or crinine, dominated alkaloid metabolism in most of the populations. With exception of one population, where the separate individuals showed variable alkaloid profiles (dominated by crinine or haemanthamine) the individuals of the rest of populations have identical and characteristic alkaloid profiles. Some populations showed remarkable differences in respect to their alkaloid pattern-type of biosynthesis, main alkaloids and number of alkaloids. Populations dominated by galanthamine type alkaloids were found as well. These data demonstrate that like the morphological features, the alkaloid metabolism of G. elwesii is also variable.

  10. 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.

  11. Phytotoxicity Assessment of Certain Phytochemical Products Containing Pyrrolizidine Alkaloids

    Directory of Open Access Journals (Sweden)

    Cristina Șeremet Oana

    2013-10-01

    Full Text Available Introduction: Tussilago farfara (coltsfoot, Petasites hybridus (common butterbur, Senecio vernalis (eastern groundsel and Symphytum officinale (comfrey are species traditionally used in phytotherapy that besides the therapeutic compounds contain toxic pyrrolizidine alkaloids (PAs. The aim of the paper is to determine the total PAs content and the phytotoxicity of the above species. Material and methods: The quantitative determination of pyrrolizidine alkaloids is based on the stoichiometric reaction of protonated alkaloids with methyl orange. In acidic conditions the dye is released from the complex and its color is assessed spectrophotometrically using a linear regression curve of senecionine as a standard. The phytotoxicity was assessed by Triticum bioassay that studies the effect of the extracts (0.001-5.00%, w/v upon root elongation (inhibitory concentration - IC50 and on the karyokinetic film. Results: The highest amount of total PAs was found in Senecio vernalis (654.8 ± 35.96 μg/g dry plant and the lowest in Petasites hybridus. The lowest IC50 was found for Tussilago farfara followed by Petasites hybridus, Senecio vernalis, and Symphytum officinale. The results were supported by microscopic examination. Conclusions: The results of the spectrophotometric assay are consistent with the ones found in the literature. All extracts inhibited the elongation of the main root of wheat caryopses, however, no correlation between phytotoxicity and the PAs concentration could be emphasized

  12. New bisbenzylisoquinoline alkaloid from Laureliopsis philippiana

    DEFF Research Database (Denmark)

    Stærk, Dan; Thi, Loi Pham; Rasmussen, Hasse Bonde

    2009-01-01

    Phytochemical investigation of Laureliopsis philippiana resulted in isolation of a new bisbenzylisoquinoline alkaloid (1) named laureliopsine A. The structure was established by spectroscopic methods, including 2D homo- and heteronuclear NMR experiments. This finding of a bisbenzylisoquinoline...... alkaloid in Laureliopsis supports its close relationship to Atherosperma and its taxonomic segregation from Laurelia....

  13. Alkaloids from the Roots of Saccopetalum prolificum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new alkaloid, named prolifine (1), was isolated along with four known alkaloids, liriodenine (2), 6-hydroxyonychine (3), isooncodine (4) and discretamine (5) from the roots of Saccopetalum prolificum. The structure of 1 was elucidated on the basis of spectroscopic and chemical methods.

  14. Plant alkaloids of the polymethyleneamine series

    Energy Technology Data Exchange (ETDEWEB)

    Rogoza, Ludmila N; Salakhutdinov, Nariman F; Tolstikov, Genrikh A [N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2005-04-30

    The published data on the structures and biological activities of the plant alkaloids of the biogenic polymethyleneamine series, viz., putrescine (1,4-diaminobutane), spermidine (1,8-diamino-4 -azaoctane), and spermine (1,12-diamino-4,9-diazadodecane), are considered and systematised. The structures and biological activities of some synthetic analogues of these alkaloids are also presented.

  15. Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae)

    Science.gov (United States)

    Zelenski, S G

    1977-11-01

    A phytochemical investigation of an alcoholic extract of the petioles of Nelumbo lutea resulted in the identification of the alkaloids N-methylasimilobine, anonaine, and roemerine. The alkaloids nuciferine, armepavine, N-nornuciferine, and N-norarmepavine, previously previously reported in the whole plant, were also identified.

  16. Alkaloids of some Asian Sedum species

    NARCIS (Netherlands)

    Kim, JH; THart, H; Stevens, JF

    1996-01-01

    The leafy parts of 16 Asian species belonging to the three sections of Sedum were investigated for the presence of alkaloids. Only in seven species of Sedum sect. Sedum were alkaloids found. Sedum bulbiferum, S. japonicum, S. lepidopodium, S. morrisomensis, S. oryzifolium, S. polytrichoides and S. s

  17. Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Yu, B W; Meng, L H; Chen, J Y; Zhou, T X; Cheng, K F; Ding, J; Qin, G W

    2001-07-01

    Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.

  18. Piperidine alkaloids: human and food animal teratogens.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Brown, David R

    2012-06-01

    Piperidine alkaloids are acutely toxic to adult livestock species and produce musculoskeletal deformities in neonatal animals. These teratogenic effects include multiple congenital contracture (MCC) deformities and cleft palate in cattle, pigs, sheep, and goats. Poisonous plants containing teratogenic piperidine alkaloids include poison hemlock (Conium maculatum), lupine (Lupinus spp.), and tobacco (Nicotiana tabacum) [including wild tree tobacco (Nicotiana glauca)]. There is abundant epidemiological evidence in humans that link maternal tobacco use with a high incidence of oral clefting in newborns; this association may be partly attributable to the presence of piperidine alkaloids in tobacco products. In this review, we summarize the evidence for piperidine alkaloids that act as teratogens in livestock, piperidine alkaloid structure-activity relationships and their potential implications for human health.

  19. A Facile Synthesis of Pyrrolidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    SHAO Zhi-Hui; CHEN Jing-Bo; WANG Cheng-Ying; LIU Xiao-Long; REN Zhou-Yang; TU Yong-Qiang; ZHANG Hong-Bin

    2003-01-01

    @@ The Amaryllidaceae alkaloids have attracted considerable attention for their interesting biological activities. [1] Many of these tyrosine derived alkaloids[2] incorporate a hexahydroindole moiety in the structural skeletons. New approaches towards the synthesis of hexahydroindole core have been a topical interest for the synthetic community.Herein we report an experimentally very simple method for the synthesis of hexahydroindole by aminocylization. Four kinds of N-substituted have been demonstrate to be effective to this cyclization. The results were summarized in Figure 1.

  20. Studies on Preparation and Dissolution Test in vitro of Intragastric Floating Two-chamber Osmotic Pump Tablets of Total Alkaloids of Coptis chinensis and Evodia rutaecarpa%连萸总生物碱胃滞留双室渗透泵片的制备及体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    方瑜; 史清文

    2011-01-01

    目的:对连萸总生物碱胃滞留双室渗透泵片(TCOPT)的制备方法进行研究,并考察其体外释放度.方法:以释放度为评价指标,采用正交设计实验优化处方与工艺.结果:最佳处方为:膨胀剂为PEO(Mw 5000000)与HPMC混合物(4∶1),用量50 mg,助推层渗透剂氯化钠用量为20 mg,包衣液致孔剂PEG 400用量10%.包衣增重9%.释药行为符合零级方程,具有明显的控释特征.结论:TCOPT具有良好的体外控释效果,可进一步进行体内释药行为考察.%Objective :To study prescription and technique of intragastric floating mo-chamber osmotic pump tablets (TCOPT)of total alkaloids of Coptis chinensis and Evodia rutaecarpa and inspect release property in vitro.Methods:The orthogonal experiment was designed to screen prescription and technique.Results :The optimization of prescription and technique were as follows:the expanding agent was a mixture of PEO and HPMC as a ratio of4:1 ;the osmotic agent in propelling layer contained sodium chloride 20 mg, PEG 400 in the cellulose acetate, 10% ;coating membrane in core tablet,9%.The release behavior of TCOPT coincidented with zero-level equation well and the character of controlled-release was transparent.Conclusion :TCOPT has good effect of controlled-release in vitro and the release behavior in vivo need to be inspected.

  1. Genetic variation in alkaloid accumulation in leaves of Nicotiana

    Institute of Scientific and Technical Information of China (English)

    Bo SUN; Fen ZHANG; Guo-jun ZHOU; Guo-hai CHU; Fang-fang HUANG; Qiao-mei WANG; Li-feng JIN; Fu-cheng LIN; Jun YANG

    2013-01-01

    Alkaloids are plant secondary metabolites that are widely distributed in Nicotiana species and contribute greatly to the quality of tobacco leaves. Some alkaloids, such as nornicotine and myosmine, have adverse effects on human health. To reduce the content of harmful alkaloids in tobacco leaves through conventional breeding, a genetic study of the alkaloid variation among different genotypes is required. In this study, alkaloid profiles in leaves of five Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six alkaloids were identified from al six genotypes via gas chromatograph-mass spectrometry (GC-MS). Significant differences in alkaloid content were ob-served both among different leaf positions and among cultivars. The contents of nornicotine and myosmine were positively and significantly correlated (R2=0.881), and were also separated from those of other alkaloids by clustering. Thus, the genotype plays a major role in alkaloid accumulation, indicating a high potential for manipulation of alkaloid content through traditional breeding.

  2. Genetic variation in alkaloid accumulation in leaves of Nicotiana.

    Science.gov (United States)

    Sun, Bo; Zhang, Fen; Zhou, Guo-jun; Chu, Guo-hai; Huang, Fang-fang; Wang, Qiao-mei; Jin, Li-feng; Lin, Fu-cheng; Yang, Jun

    2013-12-01

    Alkaloids are plant secondary metabolites that are widely distributed in Nicotiana species and contribute greatly to the quality of tobacco leaves. Some alkaloids, such as nornicotine and myosmine, have adverse effects on human health. To reduce the content of harmful alkaloids in tobacco leaves through conventional breeding, a genetic study of the alkaloid variation among different genotypes is required. In this study, alkaloid profiles in leaves of five Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six alkaloids were identified from all six genotypes via gas chromatograph-mass spectrometry (GC-MS). Significant differences in alkaloid content were observed both among different leaf positions and among cultivars. The contents of nornicotine and myosmine were positively and significantly correlated (R(2)=0.881), and were also separated from those of other alkaloids by clustering. Thus, the genotype plays a major role in alkaloid accumulation, indicating a high potential for manipulation of alkaloid content through traditional breeding.

  3. Comparative Study of Alkaloid Pattern of Four Bulgarian Fumaria species.

    Science.gov (United States)

    Doncheva, Tsvetelina; Yordanova, Gabriela; Vutov, Vassil; Kostova, Nadezhda; Philipov, Stefan

    2016-02-01

    The alkaloid pattern of four Fumaria species (Fumaria kralikii, Fumaria rostellata, Fumaria schleicherii, Fumaria thureii) growing in Bulgaria was investigated by GC-MS and twenty isoquinoline alkaloids were determined. Phytochemical investigation of the alkaloid composition on Fumaria thuretii Boiss was made for the first time. The alkaloid profile of the species was compared at two levels, between different species and within two species from different habitats. Two chemotypical groups, based on the types of isoquinoline alkaloids were suggested. To group A belong species F. kralikii, F. rostellata (F. r. 1) and F. thuretii containing more than 50% spirobenzylisoquinoline alkaloids of the crude alkaloid mixtures. To group B belong species F. rostellata (F. r. 2) and F. schleicherii containing more than 40% protopine alkaloids and relatively high percentage phthaldeisoquinoline alkaloids (11-19%). In group A phthaldeisoquinoline alkaloids were not detected.

  4. A straightforward synthetic entry to cleavamine-type indole alkaloids by a ring-closing metathesis-vinyl halide Heck cyclization strategy.

    Science.gov (United States)

    Bennasar, M-Lluïsa; Solé, Daniel; Zulaica, Ester; Alonso, Sandra

    2011-04-15

    An indole-templated ring-closing metathesis has been used to create the central nine-membered ring of the cleavamine-type alkaloids. A subsequent intramolecular vinyl halide Heck reaction upon the resulting azacyclononene ring completes the assembly of the strained 1-azabicyclo[6.3.1]dodecane framework of the alkaloids. The usefulness of the approach is illustrated with the synthesis of (±)-cleavamine and (±)-dihydrocleavamine.

  5. Total synthesis of (-)-oseltamivir by domino reactions [Síntese total do (-)-oseltamivir (Tamiflu®) por reações do tipo dominó

    OpenAIRE

    Fernando de Carvalho da Silva

    2009-01-01

    This digest report the total synyhesis of (‐)‐oseltamivir (Tamiflu®) by three “one‐pot” operations like domino reactions. This article was published by Ishikawa e co‐workers in Angewandte Chemie, International Edition. This molecule is a neuraminidase inhibitor used in the treatment against avian H5N1 influenza virus.

  6. Bromopyrrole Alkaloids from Okinawan Marine Sponges Agelas spp.

    Science.gov (United States)

    Tanaka, Naonobu; Kusama, Taishi; Kashiwada, Yoshiki; Kobayashi, Jun'ichi

    2016-01-01

    In our continuing study for structurally and biogenetically interesting natural products from marine organisms, Okinawan marine sponges Agelas spp. were investigated, resulting in the isolation of 18 unique alkaloids including five dimeric bromopyrrole alkaloids (1-5), ten monomeric bromopyrrole alkaloids (6-15), and three conjugates of monomeric bromopyrrole alkaloid and hydroxykynurenine (16-18). In this mini-review, the isolation, structure elucidation, and antimicrobial activities of these alkaloids are summarized.

  7. 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.

  8. Norditerpenoid Alkaloids from Aconitum spicatum Stapf

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To search for pharmacologically and structurally interesting substances from traditional Chinese medicines,we investigated the chemical compounds of Aconitum spicatum Stapf. Two new norditerpenoid alkaloids,namely spicatine A (compound 1) and spicatine B (compound 2), as well as 11 known norditerpenoid alkaloids were isolated from the CHCl3 portion of the 90% ethanol extract of the roots of A. spicatum. The structures of the alkaloids were characterized on the basis of their spectral data, One of the isolated compounds showed significant cytotoxic activities (IC50 values < 200 μmol/L) against the HL-60 cell line.

  9. Racemic alkaloids from the fungus Ganoderma cochlear.

    Science.gov (United States)

    Wang, Xin-Long; Dou, Man; Luo, Qi; Cheng, Li-Zhi; Yan, Yong-Ming; Li, Rong-Tao; Cheng, Yong-Xian

    2017-01-01

    Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma cochlear. The chemical structures of new compounds were elucidated on the basis of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were assigned by ECD calculations. Biological activities of these isolates against renal fibrosis were accessed in rat normal or diseased renal interstitial fibroblast cells. Importantly, the plausible biosynthetic pathway for this class of alkaloids was originally proposed.

  10. Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges.

    Science.gov (United States)

    Sfecci, Estelle; Lacour, Thierry; Amade, Philippe; Mehiri, Mohamed

    2016-04-09

    Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given.

  11. Marine Pyridoacridine Alkaloids: Biosynthesis and Biological Activities.

    Science.gov (United States)

    Ibrahim, Sabrin R M; Mohamed, Gamal A

    2016-01-01

    Pyridoacridines are a class of strictly marine-derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti-HIV, and anti-parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assignment.

  12. Isoquinoline and isoindole alkaloids from Menispermum dauricum.

    Science.gov (United States)

    Zhang, Xiaoqi; Ye, Wencai; Zhao, Shouxun; Che, Chun-Tao

    2004-04-01

    Three isoquinoline alkaloids and an isoindole alkaloid, along with eight known compounds, were isolated from the roots of Menispermum dauricum (Menispermacese). The alkaloids were characterized as 7-hydroxy-6-methoxy-1(2H)-isoquinolinone, 6,7-dimethoxy-N-methyl-3,4-dioxo-1(2H)-isoquinolinone, 1-(4-hydroxybenzoyl)-7-hydroxy-6-methoxy-isoquinoline and 6-hydroxy-5-methoxy-N-methylphthalimide, on the basis of spectral evidence including 1D- and 2D-NMR and MS analyses.

  13. Enrichment and purification of six Aconitum alkaloids from Aconiti kusnezoffii radix by macroporous resins and quantification by HPLC-MS.

    Science.gov (United States)

    Liu, Jingjing; Li, Qing; Liu, Ran; Yin, Yidi; Chen, Xiaohui; Bi, Kaishun

    2014-06-01

    Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine are six main Aconitum alkaloids from traditional Chinese medicine, Aconiti kusnezoffii radix, which possess highly bioactive as well as highly toxic character for medicinal use. In the present study, for the purpose of better utilizing the toxic herbal material, the performance characteristics of NKA-II, D101, X-5, AB-8, S-8, HPD722 and HPD750 macroporous resins for the enrichment and purification of these six Aconitum alkaloids were critically evaluated. Results showed that NKA-II offered the best adsorption and desorption capacities for six Aconitum alkaloids among the seven macroporous resins tested, which were affected significantly by the pH value. Subsequently, dynamic adsorption and desorption experiments had been carried out with the column packed by NKA-II resin to optimize the separation process of six Aconitum alkaloids. After one run treatment with NKA-II resin, the content of total six Aconitum alkaloids were increased from 5.87% to 60.3%, the recovery was 75.8%. Meanwhile, a validated HPLC-MS method had been developed to qualitative and quantitative these six Aconitum alkaloids. This method would provide scientific references to the large-scale production of six Aconitum alkaloids from Aconiti kusnezoffii radix or other plants and might also expand the secure application of these highly toxic components for pharmacy.

  14. Application of a Decomposition Strategy to the Optimal Synthesis/Design and Operation of a Fuel Cell Based Total Energy System

    OpenAIRE

    2002-01-01

    A decomposition methodology based on the concept of â thermoeconomic isolationâ applied to the synthesis/design and operational optimization of a stationary cogeneration proton exchange membrane fuel cell (PEMFC) based total energy system (TES) for residential/commercial applications is the focus of this work. A number of different configurations for the fuel cell based TES were considered. The most promising set based on an energy integration analysis of candidate configurations was devel...

  15. Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis.

    Science.gov (United States)

    Koolen, Hector H F; Pral, Elizabeth M F; Alfieri, Silvia C; Marinho, Jane V N; Serain, Alessandra F; Hernández-Tasco, Alvaro J; Andreazza, Nathalia L; Salvador, Marcos J

    2017-02-01

    Five alkaloids, in addition to hydroxytyrosol and uridine, were isolated from aerial parts of Alternanthera littoralis P. Beauv. Among the isolated compounds, alternamide A was an unusual tricyclic alkaloid with a bridged benzoazepine core. All isolated alkaloids have a catechol moiety, indicating a possible common biosynthetic route. Their structures were established by 1D and 2D NMR spectroscopy in combination with extensive tandem MS experiments by collisional induced dissociation (CID). The antiprotozoal activity of the isolated compounds was assayed against trypomastigote forms of Trypanosoma cruzi and amastigotes of Leishmania amazonensis. Alternamine A was the most active compound, reducing markedly the viability of both parasites. Antioxidant capacities evaluated by ORACFL assay showed that the isolated alkaloids (mainly alternamide B) contributed to the high activity recorded for the ethanolic crude extract; possibly, the catechol moiety present in all structures plays a central role in this result.

  16. Anxiolytic Activity of Diterpene Alkaloid Songorine.

    Science.gov (United States)

    Nesterova, Yu V; Povet'eva, T N; Suslov, N I; Shults, E E; Ziuz'kov, G N; Aksinenko, S G; Afanas'eva, O G; Krapivin, A V; Kharina, T G

    2015-09-01

    Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect.

  17. Steroidal alkaloid toxicity to fish embryos.

    Science.gov (United States)

    Crawford, L; Kocan, R M

    1993-02-01

    Embryos of two species of fish were evaluated for their suitability as model systems for steroidal alkaloid toxicity, the Japanese rice fish, medaka (Oryzius latipes) and the rainbow trout (Oncorhynchus mykiss). Additionally, the equine neurotoxic sesquiterpene lactone repin, was also tested. A PROBIT program was used to evaluate the EC1, EC50 and EC99 as well as the associated confidence limits. The steroidal alkaloids tested were the Solanum potato glycoalkaloids alpha-chaconine, alpha-solanine, the aglyclones solanidine and solasodine and the Veratrum alkaloid, jervine. Embryo mortality, likely due to structural or functional abnormalities in the early development stages of the embryo, were the only response observed in both species. The rainbow trout exhibited a toxic response to chaconine, solasidine, repin and solanine but the medaka embryos were only affected by the compounds, chaconine and solanine. Rainbow trout may indeed serve as a good lower vertebrate model for studying the toxicity of steroidal alkaloids.

  18. Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated ketones: Construction of a key intermediate for the total synthesis of zoanthamine

    DEFF Research Database (Denmark)

    Nielsen, Thomas Eiland; Tanner, David Ackland

    2002-01-01

    (E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesi...

  19. Polycyclic alkaloids via transannular Mannich reactions

    DEFF Research Database (Denmark)

    Vital, Paulo; Hosseini, Masood; Shanmugham, M. S.

    2009-01-01

    The tricyclic compound 13, representing the framework of the cylindricine 4 and lepadiformine 5 alkaloids, was prepared in a single operation via the first example of a transannular Mannich reaction involving a macrocyclic diketoamine 12.......The tricyclic compound 13, representing the framework of the cylindricine 4 and lepadiformine 5 alkaloids, was prepared in a single operation via the first example of a transannular Mannich reaction involving a macrocyclic diketoamine 12....

  20. 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.

  1. Two new diterpene alkaloids from Delphinium chrysotrichum

    Institute of Scientific and Technical Information of China (English)

    Yang Qing He; Xiao Mei Wei; Yi Li Han; Li Ming Gao

    2007-01-01

    Chemical investigation on the ethanol extract from the whole plants of Delphinium chrysotrichum resulted in the isolation of two new diterpene alkaloids named delphatisine A (1) and delphatisine B (2), respectively. The structures of the new compounds were deduced on the basis of their spectral data (IR, HREIMS, EIMS, 1D, 2D-NMR). This is the first report on the isolation of diterpenoid alkaloids from the D. Chrysotrichum.

  2. Pyrrolizidine alkaloids from Heliotropium transoxanum Bunge

    Directory of Open Access Journals (Sweden)

    M. R. Delnavazi

    2016-02-01

    Full Text Available Background and objectives: The plants belonging to the genus Heliotropium L. (Boraginaceae are the main sources of toxic pyrrolizidine alkaloids (PAs. In the present study, we have investigated the PAs of the aerial parts of Heliotropium transoxanum Bunge, a perennial species native to Iran. Methods: Silica gel column chromatography and silica gel PTLC were applied for the isolation of PAs present in the total methanol extract of H. transoxanum. The structures of the isolated compounds were identified using 1H-NMR, 13C-NMR and EIMS spectral analyses. Results: Three PAs, heliotrine (1, lasiocarpine (2 and heliotrine N-oxide (3,with known mutagenic and genotoxic properties, were isolated from the aerial parts of H. transoxanum. Conclusion: The results of this study on the presence of toxic PAs in H. transoxanum introduce this herb as a poisonous species and also suggest it as an appropriate source for the isolation of heliotrine and lasiocarpine for further toxicological and pharmacological studies.

  3. Effects of total alkaloids of Aconitum sungpanens Hand-Mazz on morphine-induced behavioral senitization and withdrawal sympotoms of morphine-dependence%松潘乌头总碱对吗啡行为敏化及其依赖戒断症状的影响

    Institute of Scientific and Technical Information of China (English)

    李敏; 王建治; 刘秀花; 焦海胜

    2012-01-01

    目的 研究松潘乌头总碱(TAA)对吗啡行为敏化及其依赖戒断症状的影响.方法 小鼠皮下注射吗啡10 mg/(kg.d),连续7d,建立吗啡诱导的小鼠行为敏化模型,观察TAA对行为敏化形成和表达的影响,恒量法和剂量递增法建立小鼠及大鼠吗啡依赖模型,观察TAA对吗啡依赖动物戒断症状的影响.结果 TAA(1.5~3.0 mg/kg)可抑制小鼠吗啡行为敏化的形成和表达过程;对吗啡依赖动物戒断评分值、体重下降均有明显抑制作用.结论 TAA可阻止吗啡成瘾行为的形成,可改善吗啡依赖动物的戒断症状,TAA对吗啡依赖可能有一定的干预作用.%Objective To study the effects of total alkaloids of Aconitum sungpanens Hand-Mazz (TAA) on morphine-induced behavioral sensitizations in mice and its effects on the withdrawal symptoms of morphine-dependence in mice and rats. Methods Mice were made behavioral sensi-tization to morphine by subcutaneous injection of 10 mg/(kg·d) morphine for 7 days, and treated with combination of morphine and TAA to investigate the effects of TAA on the sensitization to morphine. Morphine-dependent models were administrated by a constant and a gradual increasing dosage in mice and rats, and followed by the treatment of TAA. The withdrawal syndromes were scored spontaneous withdrawal after stop administration of morphine and after naloxone precipitation. Results TAA obviously blocked the development and expression of behavioral sensitization to morphine in mice. It also could inhibit the withdrawal syndromes and body weight loss in morphine-dependent mice and rats. Conclusion TAA can inhibit the development of morphine addiction behavior and morphine-withdrawal syndromes.

  4. Analysis of Indole Alkaloids from Rhazya stricta Hairy Roots by Ultra-Performance Liquid Chromatography-Mass Spectrometry.

    Science.gov (United States)

    Akhgari, Amir; Laakso, Into; Seppänen-Laakso, Tuulikki; Yrjönen, Teijo; Vuorela, Heikki; Oksman-Caldentey, Kirsi-Marja; Rischer, Heiko

    2015-12-17

    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.

  5. 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.

  6. 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.

  7. 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.

  8. HPLC quantification of alkaloids from Haplophyllum extracts and comparison with their cytotoxic properties.

    Science.gov (United States)

    Fiot, Julien; Jansen, Olivia; Akhmedjanova, Valentina; Angenot, Luc; Balansard, Guy; Ollivier, Evelyne

    2006-01-01

    An efficient system for the analysis of total alkaloids extracted from the aerial parts from different species of genus Haplophyllum (Rutaceae) by HPLC on a reversed-phase column is described. The HPLC method described was validated for its specificity, linearity and precision using external standards (haplopine, skimmianine and haplamine). The chromatographic conditions allowed the separation of alkaloids and the quantification of haplopine, skimmianine and haplamine in different samples of species of Haplophyllum collected in Uzbekistan. The alkaloidal contents of samples were compared with their in vitro cytotoxic properties against two cancer cell lines (HeLa and HCT-116). The cytotoxicity of extracts was correlated with the concentration of haplopine, skimmianine or haplamine in aerial parts of species of Haplophyllum.

  9. Improved method for the determination of oxindole alkaloids in Uncaria tomentosa by high performance liquid chromatography.

    Science.gov (United States)

    Ganzera, M; Muhammad, I; Khan, R A; Khan, I A

    2001-07-01

    This Paper describes an improved HPLC method for the determination of pentacyclic oxindole alkaloids in Uncaria tomentosa (Cat's Claw). Six of the isomeric compounds could be baseline separated at room temperature within less than 30 min by using 3 microm C-18 column material and a mobile phase consisting of 10 mM phosphate buffer at pH 7.0 and acetonitrile. At a wavelength of 245 nm all standard compounds could be detected at concentrations as low as 0.63 microg/ml. Different samples of U. tomentosa bark and market products containing Cat's Claw were extracted with a modified procedure ensuring the integrity of the alkaloids and analyzed successfully. The results indicated accuracy and consistency of the new method, and showed variations in the total alkaloid content in products from 0.156 to 0.962%.

  10. Concise stereoselective synthesis of oxaspirocycles with 1-tosyl-1,2,3-triazoles: application to the total syntheses of (±)-Tuberostemospiroline and (±)-stemona-lactam R.

    Science.gov (United States)

    Fu, Junkai; Shen, Hongjuan; Chang, Yuanyuan; Li, Chuangchuang; Gong, Jianxian; Yang, Zhen

    2014-09-26

    A 4-substituted-1-tosyl-1,2,3-triazole-based stereoselective synthesis of structurally diverse oxaspirocycles is reported. The synthesis involves Rh-catalyzed loss of nitrogen from 4-substituted-1-tosyl-1,2,3-triazoles, Grignard reaction, and a ring-closing metathesis reaction as key steps. By employing readily available and stable 4-substituted-1-tosyl-1,2,3-triazoles as surrogates of diazo compounds and nitrogen sources, two types of oxaspirocycles were obtained. The latter compounds, which contain adjacent nitrogen stereocenters, could serve as the core structures of many natural products. This chemistry has been successfully applied to the total syntheses of (±)-tuberostemospiroline and (±)-stemona-lactam R.

  11. The Effect of Prolonged Fasting on Total Lipid Synthesis and Enzyme Activities in the Liver of the European Eel (Anguilla anguilla)

    DEFF Research Database (Denmark)

    Abraham, S. A.; Hansen, Heinz Johs. Max; Hansen, F.N.

    1984-01-01

    The extent of fatty acid synthesis from [1-14C]acetate in liver slices was reduced 6-fold when eels were fasted for 1-7 wk and 20-fold when fasted for 39 wk, thereafter hepatic lipogenesis seemed to remain constant for up to 95 wk of fasting. After a 1-3 wk fast some hepatic enzyme activities were...... total lipid synthesis and lipogenic enzyme activity in eel liver was 30.degree. C....... reduced (acetyl-CoA carboxylase decreased 2-fold and fatty acid synthetase declined 5-fold); others remained unchanged (G-6-P dehydrogenase, 6-phosphogluconate dehydrogenase, .alpha.-glycerol phosphate dehydrogenase as well as malic enzyme and ATP-citrate lyase). The optimum temperature for measuring both...

  12. Bringing the science of proteins into the realm of organic chemistry: total chemical synthesis of SEP (synthetic erythropoiesis protein).

    Science.gov (United States)

    Kent, Stephen B H

    2013-11-11

    Erythropoietin, commonly known as EPO, is a glycoprotein hormone that stimulates the production of red blood cells. Recombinant EPO has been described as "arguably the most successful drug spawned by the revolution in recombinant DNA technology". Recently, the EPO glycoprotein molecule has re-emerged as a major target of synthetic organic chemistry. In this article I will give an account of an important body of earlier work on the chemical synthesis of a designed EPO analogue that had full biological activity and improved pharmacokinetic properties. The design and synthesis of this "synthetic erythropoiesis protein" was ahead of its time, but has gained new relevance in recent months. Here I will document the story of one of the major accomplishments of synthetic chemistry in a more complete way than is possible in the primary literature, and put the work in its contemporaneous context.

  13. Synthetic and DFT studies towards a unified approach to phlegmarine alkaloids: aza-Michael intramolecular processes leading to 5-oxodecahydroquinolines.

    Science.gov (United States)

    Bradshaw, Ben; Luque-Corredera, Carlos; Saborit, Gisela; Cativiela, Carlos; Dorel, Ruth; Bo, Carles; Bonjoch, Josep

    2013-10-04

    A diastereoselective synthesis of cis-5-oxodecahydroquinolines is described in which three stereocenters are generated in a one-pot reaction. The reaction involves a lithium hydroxide-promoted Robinson annulation/intramolecular aza-Michael domino process from an achiral acyclic tosylamine-tethered β-keto ester. The development and scope of this reaction was facilitated through the use of DFT-based mechanistic studies, which enabled the observed diastereodivergent course of the azacyclization to be rationalized. The varying stereochemistry and stability of the resulting decahydroquinolines was found to depend on whether a β-keto ester or ketone were embedded in the substrates undergoing aminocyclization. This synthetic approach gave access not only to both diastereomeric cis-decahydroquinolines from the same precursor, but also to the corresponding trans isomers, through an epimerization processes of the corresponding N-unsubstituted cis-5-oxodecahydroquinolines. The described methodology provides advanced building-blocks with the three relative stereochemistries required for the total synthesis of phlegmarine alkaloids.

  14. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast.

    Science.gov (United States)

    Li, Yanran; Smolke, Christina D

    2016-07-05

    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.

  15. 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

  16. Antagonistic effects of total alkaloids of Lianzixin and their methyl-derivative on stretch-induced arrhythmia%莲心总碱及其甲基化物对牵张性心律失常的拮抗效应

    Institute of Scientific and Technical Information of China (English)

    马嵘; 贺斌; 赵春虎; 王嘉陵; 向继洲

    2004-01-01

    目的澄清莲心总碱(TAL)与氨基糖苷类抗生素的共同化学结构带正电的氨基是否使之具有抗牵张性心律失常的共同效应.方法通过膨胀心室腔内的球囊、夹闭升主动脉和牵拉乳头肌建立心律失常、动作电位时程的缩短和触发活动的模型.采用离体心电图、细胞内微电极和在体单相动作电位的标准技术进行记录.结果①TAL和甲基莲心总碱(TMAL)(2.5, 5 和 10 μmol·L-1)能剂量依赖性的缩短大鼠离体心脏牵张性心律失常的持续时间,从对照组的(2.16±0.38)s减少到(1.53±0.14), (0.93±0.21), (0.52±0.35)s (TAL)和(1.59±0.16), (0.94±0.21), (0.79±0.15)s (TMAL).②在麻醉豚鼠,TAL 2.3 mg·kg-1 iv和TMAL 2.6 mg·kg-1 iv能显著抑制夹闭主动脉引起的单相动作电位50%和90%复极时程的缩短及触发活动的发生率,分别从(28.9±8.1)% 减少到(5.4±1.2)%和(10.8±2.3)%.③TAL和TMAL也能显著抑制牵拉豚鼠乳头肌所致的动作电位50%和90%复极时程的缩短.结论 TAL和TMAL能抑制牵张性心律失常和牵张引起的动作电位的改变,这种作用可能是通过阻断牵张活化的离子通道实现的.%AIM To clarify whether the common chemical structure-the positive-charged amino groups of total alkaloids of Lianzixin(TAL) and aminoglycosides antibiotics renders them possessing common antagonistic effects on stretch-induced arrhythmia. METHODS The kind of arrhythmia, shortening of action potential duration(APD) and triggered activity(TA) models were established by inflating the intracavitary balloon, clamping the ascending aorta and by stretching ventricular papillary muscle, transiently. Standard techniques of electrocardiogram(ECG), monophasic action potential(MAP) and intracellular microelectrode recording were used in vivo and in vitro. RESULTS ①TAL and total methyl alkaloids of Lianzixin(TMAL) 2.5, 5 and 10 μmol·L-1 concentration-dependently reduced the persistent duration of stretch

  17. Synthesis and absolute configuration of a new 3,4-dihydro-beta-carboline-type alkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Uncaria tomentosa).

    Science.gov (United States)

    Kitajima, Mariko; Yokoya, Masashi; Takayama, Hiromitsu; Aimi, Norio

    2002-10-01

    The structure including the absolute configuration of a new glucoalkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa), was confirmed by synthesis starting from secologanin and L-tryptophan.

  18. Biological activity of alkaloids from Solanum dulcamara L.

    Science.gov (United States)

    Kumar, Padma; Sharma, Bindu; Bakshi, Nidhi

    2009-01-01

    Alkaloids are well known for their antimicrobial activity. Though all natural alkaloids come from plants, not all plants produce alkaloids. Plants of the Solanaceae family are known for their high alkaloid content. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. In the present study, those plant parts of Solanum dulcamara were selected which have been reported to produce a high content of a specific alkaloid: solanine (from unripe fruits), solasodine (from flowers) and beta-solamarine (from roots). These alkaloids were extracted from various parts of S. dulcamara by well-established methods and were screened for their antibacterial activity. Human pathogenic bacteria, viz., Enterobacter aerogenes, Escherichia coli, Staphylococcus aureus, were selected for the study. All three alkaloids inhibited the growth of E. coli and S. aureus. However, no significant activity was observed against E. aerogenes. Minimum inhibitory concentration and minimum bactericidal concentration were also evaluated.

  19. 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.

  20. 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].

  1. An Acetylenic Alkaloid from the Calcareous Sponge Leucetta sp.

    OpenAIRE

    Nicole J de Voogd; Idam Hermawan; Junichi Tanaka

    2011-01-01

    A new acetylenic alkaloid was isolated from the sponge Leucetta sp. The structure was established by analyzing spectroscopic data. The alkaloid showed cytotoxicity IC50 2.5 mg/mL against NBT-T2 cells.

  2. Rapid screening and identification of lycodine-type alkaloids in Lycopodiaceae and Huperziaceae plants by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Shan, Si-Ming; Luo, Jian-Guang; Pan, Ke; Zou, Hong-Yan; Kong, Ling-Yi

    2016-11-01

    Lycodine-type alkaloids have gained significant interest owing to their unique skeletal characteristics and acetylcholinesterase activity. This study established a rapid and reliable method using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS/MS) for comprehensive characterization of lycodine-type alkaloids for the first time. The lycodine-type alkaloids were detected successfully from Lycopodiastrum casuarinoides, Huperzia serrata and Phlegmarirus carinatus in seven plants of the Lycopodiaceae and Huperziaceae families, based on the established characteristic MS fragmentation of five known alkaloids. Furthermore, a total of 13 lycodine-type alkaloids were identified, of which three pairs of isomers were structurally characterized and differentiated. This study further improves mass analysis of lycodine-type alkaloids and demonstrates the superiority of UPLC with a high-resolution mass spectrometer for the rapid and sensitive structural elucidation of other trace active compounds. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Improved synthesis methods of standards used for quantitative determination of total isothiocyanates from broccoli in human urine

    DEFF Research Database (Denmark)

    Kristensen, Mette; Krogholm, Kirstine Suszkiewicz; Frederiksen, Hanne;

    2007-01-01

    A well-known method for quantification of isothiocyanates (ITCs) and their metabolites is the condensation reaction with 1,2-benzenedithiole to produce 1,3-benzodithiole-2-thione, which can be quantified by high-performance liquid chromatography. Standards of an ITC metabolite and 1,3-benzodithiole......-2-thione are required for this assay but are not commercially available. In the present study, we report on an improved synthesis of the ITC metabolite N-acetyl-S-(N-4-methylsulfinylbutylthiocarbamoyl)-L-cysteine and 1,3-benzodithiole-2-thione. The standards were used to quantify the urinary...

  4. Total synthesis of (+)-discodermolide: an improved endgame exploiting a Still-Gennari-type olefination with a C1-C8 beta-ketophosphonate fragment.

    Science.gov (United States)

    Paterson, Ian; Lyothier, Isabelle

    2004-12-23

    [structure: see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.

  5. 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.

  6. The Power of Biocatalysis: A One‐Pot Total Synthesis of Rhamnolipids from Butane as the Sole Carbon and Energy Source

    Science.gov (United States)

    Gehring, Christian; Wessel, Mirja; Schaffer, Steffen

    2016-01-01

    Abstract Microbially derived surfactants, so‐called biosurfactants, have drawn much attention in recent years and are expected to replace current petrochemical surfactants, owing to their environmental and toxicological benefits. One strategy to support that goal is to reduce production costs by replacing relatively expensive sugars with cheaper raw materials, such as short‐chain alkanes. Herein, we report the successful one‐pot total synthesis of rhamnolipids, a class of biosurfactants with 12 stereocenters, from butane as sole carbon and energy source through the design of a tailored whole‐cell biocatalyst. PMID:28032017

  7. [Study on optimum extraction conditions of alkaloids from Pinellia ternate].

    Science.gov (United States)

    Zeng, Jianhong; Peng, Zhengsong; Mao, Zicheng; Wei, Shuhong

    2003-05-01

    The optimum extraction conditions of alkaloids from Pinellia ternate (Thunb.) Breit were studied by orthogonal test. The results showed that the highest extraction rate of the alkaloids could be obtained by smashing the material in 60 (sieve number) of fragmentation and socking the material in 2.575 mol/L ammonia water, extracting alkaloids with 18 times as much chlorolform at room temperature for 25 hours. The highest extraction rate of alkaloids was 0.0817%.

  8. Simulation of the type of coralin alkaloid-DNA binding

    Science.gov (United States)

    Kulikov, K. G.; Koshlan, T. V.

    2015-05-01

    Interaction between a synthesized coralin protoberberine alkaloid and the DNA double helix of the calf's thymus in a salt solution is studied by optical absorption spectroscopy and spectropolarimetry. The dependence of the spectral characteristics of the alkaloid on a ratio between the DNA base pair concentration and the alkaloid molecule concentration is considered. The parameters of bonds between the coralin alkaloid and the DNA double helix are determined using modified McGhee-von Hippel equations.

  9. TOXIC PYRROLIZIDINE ALKALOIDS OF ECHIUM AMOENUM FISCH. & MEY.

    OpenAIRE

    2006-01-01

    Toxic pyrrolizidine alkaloids are present in some species of Echium (Boraginaceae). In this study petals of Echium amoenum Fisch. & Mey. (Gol-e-Gavzaban) as a popular herbal medicine in Iran, were investigated for pyrrolizidine alkaloids (PAs). The alkaloids were separated and purified by preparative TLC and characterized by IR, one and two dimensional 1H and 13C-NMR and Mass spectroscopy. Four toxic alkaloids namely: echimidine I, echimidine isomer II, 7-angeloyl retronecine III and 7-ti...

  10. Hemlock alkaloids from Socrates to poison aloes.

    Science.gov (United States)

    Reynolds, Tom

    2005-06-01

    Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous plant. Toxicity is due to a group of piperidine alkaloids of which the representative members are coniine and gamma-coniceine. The latter is the more toxic and is the first formed biosynthetically. Its levels in relation to coniine vary widely according to environmental conditions and to provenance of the plants. Surprisingly, these piperidine alkaloids have turned up in quite unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for instance, important medicinal plants, are not regarded as poisonous although some species are very bitter. Nevertheless a small number of mostly local species contain the alkaloids, especially gamma-coniceine and there have been records of human poisoning. The compounds are recognized by their characteristic mousy smell. Both acute and chronic symptoms have been described. The compounds are neurotoxins and death results from respiratory failure, recalling the effects of curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal malformation. Both acute and chronic toxicity are seen with stock in damp meadows and have been recorded as problems especially in North America. The alkaloids derive biosynthetically from acetate units via the polyketide pathway in contrast to other piperidine alkaloids which derive from lysine.

  11. Total synthesis of crocacins A, C and D: new antibiotics isolated from Chondromyces crocatus and Chondromyces pediculatus; Sinteses totais das crocacinas A, C e D: novos antibioticos isolados de Chondromyces crocatus e Chondromyces pediculatus

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Luciana G. de; Dias, Luiz C.; Rosso, Giovanni B. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Inst. de Quimica]. E-mail: luciana@iqm.unicamp.br

    2008-07-01

    This review describes the endeavors that led to the total synthesis of a novel class of antibiotic compounds: the crocacins A-D. Other aspects such as isolation, structural elucidation as well as the biological activities are also presented. (author)

  12. 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.

  13. Improved total synthesis and biological evaluation of potent apratoxin S4 based anticancer agents with differential stability and further enhanced activity.

    Science.gov (United States)

    Chen, Qi-Yin; Liu, Yanxia; Cai, Weijing; Luesch, Hendrik

    2014-04-10

    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 apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (1c) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.

  14. The Double-Bond Configuration of Corynanthean Alkaloids and Its Impact on Monoterpenoid Indole Alkaloid Biosynthesis.

    Science.gov (United States)

    Eckermann, Ruben; Gaich, Tanja

    2016-04-11

    Experimental evidence is provided for the coherence of the double-bond geometry and the occurrence of "secondary cyclizations" in the biosynthesis of monoterpenoid indole alkaloids. Biosynthetically, akuammiline, C-mavacurine, and Strychnos alkaloids are proposed to be derived from the corynanthean alkaloid geissoschizine, a key intermediate in the biosynthetic pathway of these monoterpenoid indole alkaloids. This process occurs by so-called "secondary cyclizations" from geissoschizine or its derivatives. Although corynanthean alkaloids like geissoschizine incorporate E or Z double bonds located at C19-C20, the alkaloids downstream in the biosynthesis exclusively exhibit the E double bond. This study shows that secondary cyclizations preferentially occur with the E isomer of geissoschizine or its derivatives. This is attributed to the flexibility of the quinolizidine system of the corynanthean alkaloids, which can adopt a cis or trans conformation. For the secondary cyclization to take place, the cis-quinolizidine conformation is required. Experimental evidence supports the hypothesis that the E double bond of geissoschizine induces the cis conformation, whereas the Z double bond induces the trans conformation, which prohibits secondary cyclization of the Z compounds.

  15. Absorption characteristic of total alkaloids from Sophora flavescens and their monomers in Caco-2 cell model%苦参总生物碱及其单体在Caco-2细胞模型的吸收特征研究

    Institute of Scientific and Technical Information of China (English)

    张蕾; 冯志强; 陈孝健; 谢智勇

    2012-01-01

    目的 建立同时测定Caco-2细胞模型中苦参碱、氧化槐果碱和氧化苦参碱的HPLC方法,探讨苦参总生物碱在Caco-2细胞模型的吸收机制.方法 利用人源结肠腺癌细胞系Caco-2细胞单层模型,研究苦参碱、氧化槐果碱和氧化苦参碱由细胞绒毛膜面供给侧(AP)→基底外侧(BL)和BL→AP侧两个方向的转运过程;HPLC-UV法测定上述3个生物碱的量;计算转运参数和表观渗透系数(Papp).结果 苦参总碱给药后,苦参碱、氧化槐果碱和氧化苦参碱由AP→BL侧的Papp分别为(1.098±0.092)×10-5、(1.434±0.098)×10-5、(3.87±0.64)×10-6cm/s,由BL→AP侧的Papp分别为(1.104±0.098)×10-5、(1.034±0.079)×10-5、(2.75±0.33)×10-6 cm/s,与文献报道的单体化合物给药相比,氧化槐果碱和氧化苦参碱双向转运的Papp明显增大.苦参碱、氧化槐果碱和氧化苦参碱的表观渗透率值分别为1.01、0.72、0.71.结论 苦参总生物碱中苦参碱、氧化槐果碱和氧化苦参碱仍主要以被动吸收方式进入体内,但比各单体给药吸收更好.%Objective To establish an HPLC method for the simultaneous quantification of matrine (M), oxysophocarpine (OSP), and oxymatrine (OM), and to investigate the absorption mechanism of the total alkaloids from Sophora flavescens (TASF) in Caco-2 cell model. Methods By using Caco-2 cell monolayer model as an intestinal epithelial cell model, the transport processes of M, OSP, and OM from the apical (AP) side to the basolateral (BL) side or from BL side to AP side were studied. The contents of the three alkaloids were measured by HPLC-UV method. Transport parameters and apparent permeability coefficients (Papp) were then calculated. Results After TASF treatment, the Rvalues of M, OSP, and OM were (1.098 ±0.092) * 10-5, (1.434 ±0.098) x 10-5, and (3.87 ± 0.64) x 10-6cm/sfrom APside to BL side, and (1.104 ± 0.098) x 10~5, (1.034 ± 0. 079) x l(T5, and (2.75 ± 0.33) x 10~6cm/sfrom BLside to AP

  16. Advance Research in Total Synthesis of d-Biotin%d-生物素全合成研究进展

    Institute of Scientific and Technical Information of China (English)

    许光伟; 杨柳阳

    2014-01-01

    d-生物素目前大生产工艺以Sternbach合成路线为基础,加以不断优化形成以富马酸为起始原料,经溴代、苄胺化、环合、缩合、还原、水解、硫代、格氏、氢化、脱苄、精制得生物素。基于原料手性池的不对称合成方法发展迅速,取代Sternbach合成路线有望成为可能。%The main route of synthesis of d-biotin is based on Sternbach synthetic approach at present. After much study of process optimizing, we get an optimal process. This process started with fumaric acid, then bromination, amination, cyclization, condensation, reduction, hydrolyzation, Phosphorthioate, Grignard reaction, hydrogenation, debenzylation and refining, then d-biotin was got. With the development of the asymmetric synthesis which based on the chiral pool, it may replace Sternbach synthetic approach.

  17. 21 CFR 119.1 - Dietary supplements containing ephedrine alkaloids.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Dietary supplements containing ephedrine alkaloids... UNREASONABLE RISK § 119.1 Dietary supplements containing ephedrine alkaloids. Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended...

  18. An Unusual Pentacyclic Dinitrogenous Alkaloid from Galanthus gracilis

    OpenAIRE

    ÜNVER, Nehir; KAYA, G. İrem

    2005-01-01

    A minor alkaloid, namely gracilamine, was isolated from Galanthus gracilis. This was the first example of a pentacyclic dinitrogenous alkaloid isolated from a member of Amaryllidaceae. The structure of this alkaloid was elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, MS, UV, IR).

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. 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)

  4. Chemotaxonomy and geographical distribution of tropane alkaloids.

    Science.gov (United States)

    Griffin, W J; Lin, G D

    2000-03-01

    This review illustrates the distribution of tropane alkaloids within the families Solanaceae, Erythroxylaceae, Proteaceae, Euphorbiaceae, Rhizophoraceae, Convolvulaceae and Cruciferae. Whereas tropane alkaloids are characteristic of the genera Datura, Brugmansia (tree datura) and Duboisia of the Solanaceae, the distribution is more widespread with novel tropane derivatives in families not traditionally associated with these bases. The chemical nature of more recently discovered water-soluble calystegines and the di- and trimeric forms from the Convolvulaceae (e.g. schizanthines from Schizanthus spp.), truxillines from Bolivian coca leaves and moonines of Erythroxylum moonii are highlighted. Where possible and appropriate, links between the phytochemistry and taxonomy are discussed.

  5. Preliminary Study on Triptolide and Total Alkaloid Production of Tripterygium wilfordii Hook.f.Embryoid Culture%雷公藤胚状体培养合成雷公藤甲素与总生物碱的初步研究

    Institute of Scientific and Technical Information of China (English)

    祝传书; 冯慧娜; 薛璐莎; 杨广隶; 冯俊涛; 张兴

    2013-01-01

    Tripterygium wilfordii Hook.f.is a kind of perennial woody vine plant,and it's period of growth is very long and the content of secondary metabolites is low.The natural resources can' t supply enough needs in medicine and agriculture.The way that modem cell engineering technology which produces the secondary metabolites can solve the natural resource shortage and protect the ecological environment for wild T.wilfordii.The leaves of one-year-old T.wilfordii were used to induce calli and suspension embryoid was established using the loose calli.The results showed that green embryoid could be easily induced from calli in 1/2MS+60 mL/L coconut juice liquid medium.The separate embryoid would grow and propagate in 1/2MS +0.5 mg/L NAA.The suitable condition for embryoid culture was 1/2MS basal medium with 1.0 mg/L NAA and 30 g/L sucrose,the initial inoculum was 1.5 g/100mL,pH 5.8,and the medium volume per flask was 120 mL/250 mL after screening inoculum size,pH,the medium volume per flask.The two culture systems were obtained according to the biomass accumulation after adding endophyte fungal elicitors.The triptolide was 1.07 and 1.44 times in embryoid than that in the leaves and in the natural root bark in 1/2MS+0.5 mg/L NAA+30 g/L sucrose+Y1(leaf endophytes),pH 5.8; the total alkaloids were 17.02 and 1.46 times in embryoid than that in the leaves and in the natural root bark in 1/2MS+0.5 mg/L NAA+30 g/L sucrose+G4(root endophytes),pH 5.8.The death rate of embryoid extracts was over 90% after 72 h on Plutella xylostella L.3rd,the biological activity of embryoid extracts were the same as root bark.The content of triptolide and total alkaloid in embryoid which was induced from leaf calli matched the wild leaf and root bark,there was no significant difference of insecticidal activities between the embryoid extract and root bark.These results show that the culture of embryoid may be one of the pathways to solve the shortage of natural resource in T

  6. Alkaloid production by callous tissue cultures of Cereus peruvianus (Cactaceae).

    Science.gov (United States)

    de Oliveira, Arildo José Braz; Machado, Maria Fátima Pires da Silva

    2003-02-01

    The morphologically undifferentiated cells of nonregenerant callous tissue of Cereus peruvianus cultured in the original medium and in medium supplemented with tyrosine were used as an alkaloid source. Comparison of alkaloid production by C. peruvianus plants and by callous tissues indicated that alkaloid levels were almost twice as high in callous tissues as in shoots of C. peruvianus plants. The ratio of alkaloid concentration between mature plant and morphologically undifferentiated cells of callous tissue was 1:1.7. A relationship between culture medium containing tyrosine and alkaloid production was also observed in the callous tissues of C. peruvianus. Since increased alkaloid production may be induced by additional factors such as tyrosine, increasing levels of tyrosine or other conditions of the culture medium may be considered factors for inducing higher alkaloid production by C. peruvianus callous tissues.

  7. Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

    Science.gov (United States)

    Jiang, Qi-Wei; Chen, Mei-Wan; Cheng, Ke-Jun; Yu, Pei-Zhong; Wei, Xing; Shi, Zhi

    2016-01-01

    Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.

  8. Honatisine, a novel diterpenoid alkaloid, and six known alkaloids from Delphinium honanense and their cytotoxic activity.

    Science.gov (United States)

    He, Yang Qing; Ma, Zhan Ying; Wei, Xiao Mei; Liu, Dong Jie; Du, Bao Zhong; Yao, Bing Hua; Gao, Li Ming

    2011-11-01

    A novel diterpene alkaloid named honatisine (1) has been isolated from the whole plants of Delphinium honanense, along with six known alkaloids, siwanine E (2), isoatisine (3), atisine (4), delcorinine (5), uraphine (6), and nordhagenine A (7). Their structures were deduced on the basis of their spectral data. All of them were evaluated by a SRB assay for their cytotoxicity, and compound 1 showed a significant cytotoxic activity (IC(50) =3.16 μM) against the MCF-7 cell line.

  9. Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents.

    Science.gov (United States)

    Pan, Guojun; Zhao, Lianbo; Xiao, Na; Yang, Ke; Ma, Yantao; Zhao, Xia; Fan, Zhenchuan; Zhang, Yongmin; Yao, Qingwei; Lu, Kui; Yu, Peng

    2016-10-21

    The naturally occurring flavone 8-(6″-umbelliferyl)apigenin, a hybrid structure of apigenin and coumarin, as well as seven of its analogues were synthesized for the first time by using iodination and Suzuki coupling reactions as key steps. The synthesis of 8-(6″-umbelliferyl)-apigenin was achieved in seven linear steps from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one and 7-hydroxyl coumarine with 31% overall yield. Effects of these compounds on glucose disposal were investigated in adipocytes. All of the flavonoid and coumarin hydrids were found to have better bioactivities than their corresponding flavonoid cores. The most potent compound 15 (10 μΜ) could promote glucose consumption by 57% which exhibited similar effect as the positive control metformin at 1 mM. Moreover, fluorescence microscopy showed that four 8-(6″-umbelliferyl)apigenin analogues 2, 15, 30 and 31 could promote the 2-NBDG uptake into 3T3-L1 cells, which consist with those observed in the regulation of glucose.

  10. Total Synthesis, Stereochemical Assignment, and Field-Testing of the Sex Pheromone of the Strepsipteran Xenos peckii.

    Science.gov (United States)

    Zhai, Huimin; Hrabar, Michael; Gries, Regine; Gries, Gerhard; Britton, Robert

    2016-04-25

    The sex pheromone of the endoparasitoid insect Xenos peckii (Strepsiptera: Xenidae) was recently identified as (7E,11E)-3,5,9,11-tetramethyl-7,11-tridecadienal. Herein we report the asymmetric synthesis of three candidate stereostructures for this pheromone using a synthetic strategy that relies on an sp(3) -sp(2) Suzuki-Miyaura coupling to construct the correctly configured C7-alkene function. Comparison of (1) H NMR spectra derived from the candidate stereostructures to that of the natural sex pheromone indicated a relative configuration of (3R*,5S*,9R*). Chiral gas chromatographic (GC) analyses of these compounds supported an assignment of (3R,5S,9R) for the natural product. Furthermore, in a 16-replicate field experiment, traps baited with the synthetic (3R,5S,9R)-enantiomer alone or in combination with the (3S,5R,9S)-enantiomer captured 23 and 18 X. peckii males, respectively (mean±SE: 1.4±0.33 and 1.1±0.39), whereas traps baited with the synthetic (3S,5R,9S)-enantiomer or a solvent control yielded no captures of males. These strong field trapping data, in combination with spectroscopic and chiral GC data, unambiguously demonstrate that (3R,5S,9R,7E,11E)-3,5,9,11-tetramethyl-7,11-tridecadienal is the X. peckii sex pheromone.

  11. Histrionicotoxin alkaloids finally detected in an ant

    DEFF Research Database (Denmark)

    Jones, Tappey H.; Adams, Rachelle Martha Marie; Spande, Thomas F.

    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...

  12. A New Quinolizidine Alkaloid from Boehmeria siamensis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new quinolizidine alkaloid, 3-(4-hydroxyphenyl)-4-(3-methoxy-4-hydroxyphenyl)-3, 4-dehydroquinolizidine (1), was isolated from the ethanol extract of the whole plants of Boehmeria siamensis Craib. Its structure was elucidated on the analysis of 1D NMR and 2D NMR spectrum.

  13. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Science.gov (United States)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  14. A New Alkaloid from Isatis costata

    OpenAIRE

    Fatima, Itrat; Anis, Itrat; Ahmad, Ijaz; Malik, Abdul; Afza, Nighat

    2014-01-01

    A new alkaloid has been isolated from Isatis costata C.A.Mey. and assigned structure 1 on the basis of spectroscopic data including 1D and 2D NMR techniques. Methyl 2-acetoamidobenzoate (2), b-sitosterol (3), and ursolic acid (4) were also isolated for the first time from this species.

  15. Alkaloids from Oriciopsis glaberrima Engl. (Rutaceae).

    Science.gov (United States)

    Wansi, Jean Duplex; Wandji, Jean; Kamdem Waffo, Alain François; Ngeufa, Happi Emmanuel; Ndom, Jean Claude; Fotso, Serge; Maskey, Rajendra Prasad; Njamen, Dieudonné; Fomum, Tanee Zacharias; Laatsch, Harmut

    2006-03-01

    Two alkaloid derivatives, oriciacridone A and B, were isolated from the stem bark of Oriciopsis glaberrima (Rutaceae). The structures were elucidated by a detailed spectroscopic analysis. The extract exhibited in vitro significant antimicrobial activity against a range of micro-organisms.

  16. Eremophilanes and Pyrrolizidine Alkaloids of Senecioneae Species

    OpenAIRE

    2014-01-01

    The chemical study of two species of the tribe Senecioneae afforded two eremophilanes and two pyrrolizidine alkaloids from Se - necio subauriculatus and four modified eremophilanes from Roldana oaxacana . The chemistry of these species is in accord with that re - ported for species of Senecio and Roldana studied so far, and therefore, with the already described for the tribe Senecioneae.

  17. 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.

  18. Two New Oxoaporphine Alkaloids from Thalictrum elegans

    Institute of Scientific and Technical Information of China (English)

    梁志远; 杨小生; 汪冶; 郝小江

    2005-01-01

    Two new oxoaporphine alkaloids, 1,2,3,10-tetramethoxy-9-(2-hydroxy-4,5-dimethoxybenzyloxy)oxoaporphine (1) and 1,2,3,10-tetramethoxy-9-(4,5-dimethoxy-2-formylphenoxy)oxoaporphine (2), were isolated from Thalictrum elegans. Their structures were elucidated based on spectroscopic analysis including 1D, 2D NMR, IR and MS.

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

    Science.gov (United States)

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

    2011-02-01

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

  20. Diversity of the Mountain Flora of Central Asia with Emphasis on Alkaloid-Producing Plants

    Directory of Open Access Journals (Sweden)

    Karimjan Tayjanov

    2017-02-01

    Full Text Available The mountains of Central Asia with 70 large and small mountain ranges represent species-rich plant biodiversity hotspots. Major mountains include Saur, Tarbagatai, Dzungarian Alatau, Tien Shan, Pamir-Alai and Kopet Dag. Because a range of altitudinal belts exists, the region is characterized by high biological diversity at ecosystem, species and population levels. In addition, the contact between Asian and Mediterranean flora in Central Asia has created unique plant communities. More than 8100 plant species have been recorded for the territory of Central Asia; about 5000–6000 of them grow in the mountains. The aim of this review is to summarize all the available data from 1930 to date on alkaloid-containing plants of the Central Asian mountains. In Saur 301 of a total of 661 species, in Tarbagatai 487 out of 1195, in Dzungarian Alatau 699 out of 1080, in Tien Shan 1177 out of 3251, in Pamir-Alai 1165 out of 3422 and in Kopet Dag 438 out of 1942 species produce alkaloids. The review also tabulates the individual alkaloids which were detected in the plants from the Central Asian mountains. Quite a large number of the mountain plants produce neurotoxic and cytotoxic alkaloids, indicating that a strong chemical defense is needed under the adverse environmental conditions of these mountains with presumably high pressure from herbivores.