Rearrangements in the Mechanisms of the Indole Alkaloid Prenyltransferases*
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Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis
Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis: Rapid Access to the (Iso)Cyclocitrinol Core Christopher W. Plummer Submitted in partial fulfillment of the Requirement for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences Columbia University 2012 © 2012 Christopher Wainwright Plummer All Rights Reserved Abstract Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis: Rapid Access to the (Iso)Cyclocitrinol Core Christopher W. Plummer This thesis describes the efforts of Professor James Leighton and myself toward the synthesis of the tetracyclic core of a class of steroidal natural products known as the cyclocitrinols. Our initial work in this area was performed on racemic model systems in order to validate our ring contraction-Cope rearrangement strategy. Novel chemistry was then identified to access the functionalized core in enantio-enriched form. Finally, in line with our efforts to probe the transition state of our key tandem Claisen-Cope reaction, additional substrates were prepared supporting our proposed transition state and improving the efficiency of this transformation. Table of Contents Chapter I. Background………………………………………………………....……………1 1.1: Isolation and Characterization of the Cyclocitrinols 1 1.2: Biosynthesis and Previous Synthetic Approach 2 1.3: Retrosynthetic Analysis 5 1.4: Previous Synthetic Efforts in the Leighton Laboratory 9 Chapter II. Model Studies……………………………………………………………….….13 2.1: 1st Generation Macrolactone Approach 13 2.2: -
The Catechol-O-Methyltransferase Inhibitory Potential of Z
Revista Brasileira de Farmacognosia 25 (2015) 382–386 www .sbfgnosia.org.br/revista Original Article The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches a,b,1 a,1 a Carolina dos Santos Passos , Luiz Carlos Klein-Júnior , Juliana Maria de Mello Andrade , c a,∗ Cristiane Matté , Amélia Teresinha Henriques a Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil b Department of Pharmacochemistry, School of Pharmaceutical Sciences, Université de Genève, Genève, Switzerland c Programa de Pós-graduac¸ ão em Ciências Biológicas: Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil a b s t r a c t a r t i c l e i n f o Article history: Z-Vallesiachotamine is a monoterpene indole alkaloid that has a -N-acrylate group in its structure. Received 29 May 2015 This class of compounds has already been described in different Psychotria species. Our research group Accepted 3 July 2015 observed that E/Z-vallesiachotamine exhibits a multifunctional feature, being able to inhibit targets Available online 26 July 2015 related to neurodegeneration, such as monoamine oxidase A, sirtuins 1 and 2, and butyrylcholinesterase enzymes. Aiming at better characterizing the multifunctional profile of this compound, its effect on Keywords: cathecol-O-methyltransferase activity was investigated. The cathecol-O-methyltransferase activity was Monoterpene indole alkaloids evaluated in vitro by a fluorescence-based method, using S-(5 -adenosyl)-l-methionine as methyl donor Vallesiachotamine and aesculetin as substrate. The assay optimization was performed varying the concentrations of methyl Catechol-O-methyltransferase l Docking donor (S-(5 -adenosyl)- -methionine) and enzyme. -
Links Between Genetic Groups, Indole Alkaloid Profiles and Ecology Within the Grass-Parasitic Claviceps Purpurea Species Complex
Toxins 2015, 7, 1431-1456; doi:10.3390/toxins7051431 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Article Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex Mariell Negård 1,2, Silvio Uhlig 1,3, Håvard Kauserud 2, Tom Andersen 2, Klaus Høiland 2 and Trude Vrålstad 1,2,* 1 Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, Norway; E-Mails: [email protected] (M.N.); [email protected] (S.U.) 2 Department of Biosciences, University of Oslo, P.O. Box 1066 Blindern, 0316 Oslo, Norway; E-Mails: [email protected] (H.K.); [email protected] (T.A.); [email protected] (K.H.) 3 Department of the Chemical and Biological Working Environment, National Institute of Occupational Health, P.O. Box 8149 Dep, 0033 Oslo, Norway * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +47-2321-6247. Academic Editor: Christopher L. Schardl Received: 3 January 2015 / Accepted: 22 April 2015 / Published: 28 April 2015 Abstract: The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS. -
Endophytic Fungi: Treasure for Anti-Cancerous Compounds
International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 8, 2016 Review Article ENDOPHYTIC FUNGI: TREASURE FOR ANTI-CANCEROUS COMPOUNDS ANAND DILIP FIRODIYAa*, RAJESH KUMAR TENGURIAb aCSRD, Peoples University, Bhopal 462037, Madhya Pradesh, India, bDepartment of Botany, Govt. PG College, Rajgarh 496551, Madhya Pradesh, India Email: [email protected] Received: 22 Apr 2016 Revised and Accepted: 20 June 2016 ABSTRACT Endophytic fungi that live asymptomatically inside the plant tissues have novel bioactive metabolites exhibiting a variety of biological activities, especially against cancer. This review highlights the research progress on the production of anticancer compounds by endophytic fungi from 1990- 2015. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. The ubiquitous nature of endophytic fungi synthesise diverse chemicals with promising anticancer activity from either their original host or related species. Modification in fermentation parameters and genetic insight of endophytes may produce novel anti-cancerous compounds. Keywords: Cancer, Medicinal plants, Secondary metabolites © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION endophytic fungi detectable by high-performance liquid chromate- graphy, nuclear magnetic resonance, mass spectrophotometer and The interest in the biogenic medicines has revived throughout the X-ray crystallography and its cytotoxicity of the bioactive world, as the increase in awareness of the health hazards and compounds against cancer cell lines. The compounds with potential toxicity associated with the random use of synthetic drugs and application were also considered in the selection of antitumor antibiotics [1]. -
Hydrogen Bond-Directed Stereospecific Interactions in (A) General Synthesis of Chiral Vicinal Diamines and (B) Generation of Helical Chirality with Amino Acids
HYDROGEN BOND-DIRECTED STEREOSPECIFIC INTERACTIONS IN (A) GENERAL SYNTHESIS OF CHIRAL VICINAL DIAMINES AND (B) GENERATION OF HELICAL CHIRALITY WITH AMINO ACIDS by Hyunwoo Kim A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto © Copyright by Hyunwoo Kim, 2009 Hydrogen Bond-Directed Stereospecific Interactions in (A) General Synthesis of Chiral Vicinal Diamines and (B) Generation of Helical Chirality with Amino Acids Hyunwoo Kim Doctor of Philosophy 2009 Department of Chemistry University of Toronto ABSTRACT Hydrogen bonding interactions have been applied to the synthesis of chiral vicinal diamines and the generation of helical chirality. A stereospecific synthesis of vicinal diamines was developed by using the diaza-Cope rearrangement reaction driven by resonance-assisted hydrogen bonds (RAHBs). This process for making a wide variety of chiral diamines requires only a single starting chiral diamine, 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethane (HPEN) and aldehydes. Experimental and computational studies reveal that this process provides one of the simplest and most versatile approaches to preparing chiral vicinal diamines including not only C2 symmetric diaryl and dialkyl diamines but also unsymmetrical alkyl-aryl and aryl-aryl diamines with excellent yields and enantiopurities. Weak forces affecting kinetics and thermodynamics of the diaza-Cope rearrangement were systematically studied by combining experimental and computational approaches. These forces include hydrogen bonding effects, electronic effects, steric effects, and oxyanion effects. As an example of tuning diamine catalysts, a vicinal diamine-catalyzed synthesis of warfarin is described. Detailed mechanistic studies lead to a new mechanism involving diimine intermediates. -
Hallucinogens: a Cause of Convulsive Ergot Psychoses
Loma Linda University TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works Loma Linda University Electronic Theses, Dissertations & Projects 6-1976 Hallucinogens: a Cause of Convulsive Ergot Psychoses Sylvia Dahl Winters Follow this and additional works at: https://scholarsrepository.llu.edu/etd Part of the Psychiatry Commons Recommended Citation Winters, Sylvia Dahl, "Hallucinogens: a Cause of Convulsive Ergot Psychoses" (1976). Loma Linda University Electronic Theses, Dissertations & Projects. 976. https://scholarsrepository.llu.edu/etd/976 This Thesis is brought to you for free and open access by TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. It has been accepted for inclusion in Loma Linda University Electronic Theses, Dissertations & Projects by an authorized administrator of TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. For more information, please contact [email protected]. ABSTRACT HALLUCINOGENS: A CAUSE OF CONVULSIVE ERGOT PSYCHOSES By Sylvia Dahl Winters Ergotism with vasoconstriction and gangrene has been reported through the centuries. Less well publicized are the cases of psychoses associated with convulsive ergotism. Lysergic acid amide a powerful hallucinogen having one.-tenth the hallucinogenic activity of LSD-25 is produced by natural sources. This article attempts to show that convulsive ergot psychoses are mixed psychoses caused by lysergic acid amide or similar hallucinogens combined with nervous system -
Spatial Patterns of Claviceps Purpurea in Kentucky Bluegrass And
SPATIAL PATTERNS OF CLAVICEPS PURPUREA IN KENTUCKY BLUEGRASS AND PERENNIAL RYEGRASS GROWN FOR SEED AND EFFECT OF SOIL-APPLIED FUNGICIDES ON GERMINATION OF ERGOT SCLEROTIA J.K.S. Dung, D.L. Walenta, S.C. Alderman, and P.B. Hamm Introduction protective fungicide applications are required during Ergot, caused by the fungus Claviceps purpurea, is anthesis. Some growers experience severe ergot an important floral disease of grasses that issues even after four fungicide applications. A significantly impacts Kentucky bluegrass (KBG) and limited number of fungicides are currently available perennial ryegrass (PRG) seed production in the and new products or application strategies need to be Pacific Northwest (PNW). The fungus infects evaluated. In addition to timing fungicides during unfertilized ovaries and replaces seed with elongated anthesis, when flowers are susceptible to infection, it black fungal bodies called sclerotia, which may be possible to apply fungicides to sclerotia in overwinter in the soil and germinate to produce the field during the fall and/or as they begin to airborne ascospores in the spring. In addition to germinate in the spring before they release spores. yield losses from ergot, the repeated cleanings Soil-applied fungicides may reduce sclerotia required to remove ergot sclerotia to achieve seed germination and spore production, limiting the certification standards result in additional seed loss production of primary inoculum and subsequent as well as extra costs in time and labor. ergot infection (Hardison 1975). Although ergot is a persistent problem in PNW grass The objectives of this study were to: 1) quantify and seed production, the incidence and intensity of ergot describe the spatial patterns of ergot epidemics in epidemics can vary regionally, locally, and from commercial KBG and PRG fields in Oregon and year to year. -
Strictosidinic Acid, Isolated from Psychotria Myriantha Mull
Fitoterapia 83 (2012) 1138–1143 Contents lists available at SciVerse ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus F.M. Farias a, C.S. Passos b, M.D. Arbo c, D.M. Barros d, C. Gottfried e, V.M. Steffen c, A.T. Henriques b,⁎ a Curso de Farmácia, Universidade Federal do Pampa, BR 472 km 592, CEP 97500‐970, Uruguaiana, RS, Brazil b Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, CEP 90610‐000, Porto Alegre, RS, Brazil c Laboratório de Toxicologia, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, CEP 90610‐000, Porto Alegre, RS, Brazil d Programa de Pós-Graduação em Educação em Ciências, Química da Vida e Saúde, Universidade Federal de Rio Grande, Av. Itália, Km 8, CEP 96501‐900, Rio Grande, RS, Brazil e Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035‐003, Porto Alegre, RS, Brazil article info abstract Article history: Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic Received 20 February 2012 monoterpene indole alkaloids. These compounds are able to display a large range of effects on the Accepted in revised form 11 April 2012 central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning Available online 21 April 2012 and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. -
Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements By
Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements By Kevin Michael Allegre B.Sc., The University of Kansas, 2013 Submitted to the graduate degree program in Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Jon A. Tunge Paul R. Hanson Helena Malinakova Michael Rubin Ryan A. Altman Date Defended: 18 July 2019 The dissertation committee for Kevin M. Allegre certifies that this is the approved version of the following dissertation: Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements Chair: Jon A. Tunge Date Approved: 24 July 2019 ii Abstract Kevin M. Allegre and Jon A. Tunge Department of Chemistry, July 2019 University of Kansas Anion Relay Chemistry is a powerful tool for the rapid development of molecular complexity in an operationally simple manner. Much of the work in this field has been pioneered and developed by the Smith group, whose work has primarily focused on silicon and phosphorus Brook rearrangements to effect anion relay. Presented herein is the development of a retro-Claisen condensation protocol to effect anion relay in the synthesis of vinyl cyclopropanes, and subsequent aromatic Cope rearrangement of those vinyl cyclopropanes. This protocol provides a supplementary method of anion relay utilizing readily accessible nucleophiles, which obviates the need for synthesis of alkyl silanes or phosphines as starting materials. Chapter 1 is a review of anion relay chemistry, which focuses on through-space anion relay over 3 or more bonds. It covers both new developments and applications to total synthesis of through-space anion relay more than three bonds since the field was last reviewed by Smith in 2008. -
Elimination Reactions Are Described
Introduction In this module, different types of elimination reactions are described. From a practical standpoint, elimination reactions widely used for the generation of double and triple bonds in compounds from a saturated precursor molecule. The presence of a good leaving group is a prerequisite in most elimination reactions. Traditional classification of elimination reactions, in terms of the molecularity of the reaction is employed. How the changes in the nature of the substrate as well as reaction conditions affect the mechanism of elimination are subsequently discussed. The stereochemical requirements for elimination in a given substrate and its consequence in the product stereochemistry is emphasized. ELIMINATION REACTIONS Objective and Outline beta-eliminations E1, E2 and E1cB mechanisms Stereochemical considerations of these reactions Examples of E1, E2 and E1cB reactions Alpha eliminations and generation of carbene I. Basics Elimination reactions involve the loss of fragments or groups from a molecule to generate multiple bonds. A generalized equation is shown below for 1,2-elimination wherein the X and Y from two adjacent carbon atoms are removed, elimination C C C C -XY X Y Three major types of elimination reactions are: α-elimination: two atoms or groups are removed from the same atom. It is also known as 1,1-elimination. H R R C X C + HX R Both H and X are removed from carbon atom here R Carbene β-elimination: loss of atoms or groups on adjacent atoms. It is also H H known as 1,2- elimination. R C C R R HC CH R X H γ-elimination: loss of atoms or groups from the 1st and 3rd positions as shown below. -
Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds
Downloaded from orbit.dtu.dk on: Sep 28, 2021 Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds Bradley, Samuel Alan; Zhang, Jie; Jensen, Michael Krogh Published in: Frontiers in Bioengineering and Biotechnology Link to article, DOI: 10.3389/fbioe.2020.594126 Publication date: 2020 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Bradley, S. A., Zhang, J., & Jensen, M. K. (2020). Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds. Frontiers in Bioengineering and Biotechnology, 8, [594126]. https://doi.org/10.3389/fbioe.2020.594126 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. fbioe-08-594126 October 19, 2020 Time: 19:15 # 1 REVIEW published: 23 October 2020 doi: 10.3389/fbioe.2020.594126 Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds Samuel A. Bradley, Jie Zhang and Michael K. -
Chemical Compound Outline (Part II)
Chemical Compound Outline (Part II) Ads by Google Lil Wayne Lyrics Search Lyrics Song Wayne Dalton Wayne's Word Index Noteworthy Plants Trivia Lemnaceae Biology 101 Botany Search Major Types Of Chemical Compounds In Plants & Animals Part II. Phenolic Compounds, Glycosides & Alkaloids Note: When the methyl group containing Jack's head is replaced by an isopropyl group, the model depicts a molecule of menthol. Back To Part I Find On This Page: Type Word Inside Box; Find Again: Scroll Up, Click In Box & Enter [Try Control-F or EDIT + FIND at top of page] **Note: This Search Box May Not Work With All Web Browsers** Go Back To Chemical VI. Phenolic Compounds Compounds Part I: VII. Glycosides Table Of Contents VIII. Alkaloids Search For Specific Compounds: Press CTRL-F Keys If you have difficulty printing out this page, try the PDF version: Click PDF Icon To Read Page In Acrobat Reader. See Text In Arial Font Like In A Book. View Page Off-Line: Right Click On PDF Icon To Save Target File To Your Computer. Click Here To Download Latest Acrobat Reader. Follow The Instructions For Your Computer. Types Of Phenolic Compounds: Make A Selection VI. Phenolic Compounds: Composed of one or more aromatic benzene rings with one or more hydroxyl groups (C-OH). This enormous class includes numerous plant compounds that are chemically distinct from terpenes. Although the essential oils are often classified as terpenes, many of these volatile chemicals are actually phenolic compounds, such as eucalyptol from (Eucalytus globulus), citronellal from (E. citriodora) and clove oil from Syzygium aromaticum.