DOCSLIB.ORG

Indolizidine Alkaloids Baran Group Meeting

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Indolizidine Alkaloids Baran Group Meeting 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Me O O Background/Introduction: HO H H H HO Me 1. Isolated from a myriad of sources, including, but not limited to ants, N frogs, fungi, and trees. Me N HO H N N 2. A host of effects including, but not limited to, harvest failures, edemas, Me Me necrosis, and rashes. elaeokanine C 3. A host of activities including, but not limited to, phytotoxic, insecticidal, Me Me N antibacterial, and fungicidal. allopumiliotoxin 267A myrmicarin 215A 4. It is unclear what defines the limits of the family, however scores of rhazinilam H H natural products contain the core structure shown below. A sampling Me HO H is provided at the end of the handout. HO 5. The ring is numbered as shows below. N N OH Me Me N 8 1 Me 7 9 2 Me Me OH 6 N Me Me 4 myrmicarin 215B myrmicarin 217 5 3 allopumiliotoxin 339B Me Me OH OH H H Me OH H Syntheses Discussed (in order): H H OAc Me H OH OH N N HO O N Me N Me N H Me swainsonine N nuphar alkaloids Me H2N N indolizidine 223AB slaframine N indolizidine 209D indolizidine 223A serratinine Me tashiromine O Me Me HO H H HO H HO H OH H OH OH Me H Me N N N Me N N OH N H OH OH Me Me OH Me Me lentiginosine O pumiliotoxin 323A lepadiformine pumiliotoxin 307A pumiliotoxin 251D gephyrotoxin O OH OH O H H OH H Me H HO H H N H Me N H N N Me OH N HO H N Me H castanospermine H N H Me securinine gephyrotoxin indolizomycin O alkaloid 205B indolizidine 167B HO ipaldibine Me Me Me 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Gallagher, Tetrahedron Lett. 1995, 36, 6957. Barluenga, J. Org. Chem. 1999, 64, 3736. OTMS O OH O O ZnCl , THF, Me 2 pip. TMS – 80 to 25 ºC; Me + N NH N N slaframine CbzHN 30% CbzHN NaHCO ; N Ar 3 O Ar O O SiO2, 51% OMe nuphar alkaloids Marsden, Synlett, 2005, (16), 2528. Kibayashi, J. Am. Chem. Soc. 2000, 122, 4583. O Mechanism? HO H H 1. H2, Pd/C TFA OMOM 2. Na(Hg), Na HPO tashiromine NHOH 2 4 N 3. MsCl, TEA, DMAP 85% N Bu4NIO4 TMS O O 77% O N 4, KOtBu, THF O 69% Knapp, J. Org. Chem. 1992, 57, 4802. OMOM SePh OAc N H (TMS)3SiH, OAc lepadiformine O AIBN, PhH, MOMO N 16 hrs, N THPO THPO O 76% O slaframine Wightman, Tetrahedron, 1998, 54, 9429. Me Me Somfai, Tetrahedron. 1995, 51, 9747. O TBDPSO O TBDPSO Me Tol., ! Me H + Mechanism? O 92% O N+ N N LDA, THF, O- O – 78 ºC, Me CO t-Bu Me 1. TBAF 2 O H N CO2t-Bu Me 2. MsCl, Pyr. Me 98% H lentiginosine OH O 3. H2, Pd/C indolizidine 209D N 76% 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Goti, Tetrahedron Lett. 1994, 35, 949. Rumeson, Tetrahedron Lett. 1999, 40, 1661. H EtO 1. TMSCH MgCl OTBDPS 1. PhH, RT, H OTBDPS 2 EtO2C 7 days, 75% O (2 equiv), CeCl3 N N + OTBDPS OTBDPS N+ N 2. HCl, 86% - 2. xylenes, O O O 140 ºC, 45% Me Me Mechanism? indolizidine 167B Mechanism? lentiginosine Mariano, Tetrahedron. 2005, 61, 8888. Saegusa, Tetrahedron Lett. 1983, 24, 2881. N NHAc AcN 1. HClO4, h" H AcO OAc BnO OTBS Me3N 2. Ac2O, Pyr. TMS CsF MeO N MeO N 42% 71% gephyrotoxin Mechanism? OBn OTBS H RCM swainsonine Mechanism? OTHP OTHP castanospermine NAc 63% See "Pyridinium Photochemistry" Baran Group Meeting. Weinreb, J. Am. Chem. Soc. 1982, 104, 7065. Jefford, Helv. Chim. Act. 1986, 69, 2048. OTBS OTBS N2 DCB, ! O O H Rh(OAc)2 N N ipalbidine MeO C 82% MeO C slaframine 2 2 N 89% N OAc O O Ph Ph Angle, J. Org. Chem. 1997, 62, 8549. Tetrahedron Lett. 1993, 34, 3985. Honda, Org. Lett. 2004, 6, 87. O 1. TIPSOTf, O 1. Hoveyda- 1. NBS, AIBN O O O TEA H Grubbs H 2. TFA Me indolizidine 167B 2. LAH N N NBoc 2. CrO3, N 3. K2CO3 Bn 79% Bn Boc OH Me2Pyrazole 45% Me Mechanism? Me 57% securinine 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Montgomery, J. Am. Chem. Soc. 1999, 121, 6098. Trauner, Org. Lett. 2005, 7, 5207. O O MOM MOM Me N Pd(OAc)2, Me Me K2CO3, 47% N Me TESH, Me I Cy2P Me Ni(COD)2, 1. HF•Pyr rhazinilam N N N N 2. Li, NH PBu3, 95% 3 NMe2 O OTES 81% CO2Me CO2Me H H Me OBn Me OBn allopumiliotoxin 267A Movassaghi, Org. Lett. 2005, 7, 4423. OTf Pd dba , XPhos, Tol. O See "Nickel in Synthesis" Baran Group Meeting. 2 3 t-BuO2C OMe K3PO4, 60 ºC, 95% Me O Me Me Mori, Tetrahedron. 1998, 54, 1153. Tetrahedron Lett. 1997, 38, 3931. OMe O N Me NH OMe Me Me t-BuO H H myrmicarin 215A OMe Ni(COD)2, TESO myrmicarin 215B myrmicarin 217 N N elaeokanine C PPh3, TESH, 74% O O O Kibayashi, J. Am. Chem. Soc. 1992, 114, 10653. Me Me BnO H BnO H CrCl2, HO Sames, J. Am. Chem. Soc. 2002, 124, 6900. ibid. 2000, 122, 6321. NiCl2, O N N allopumiliotoxin 339A O DMF R R Ph I 79% R N 1. TfOH N H2N Me Pt 2. TFE, 70 ºC Back, Org. Lett. 1999, 1, 261. J. Org. Chem. 2000, 65, 4543. Me Me Mechanism? H 3. KCN Me Me H 4. NH OH Me 1. DCM 2 N rhazinilam + Ts N 40% Ts N Cl HN 2. LDA 94% Me indolizidine 167B 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Inubushi, J. Chem. Soc. Chem. Commun. 1974, 827. O'Doherty, Org. Lett. 2006, 8, 1609. Mechanism? O OTBS AcO AcO O OH NBS, H2O H H Me Me 1. LiBH4 OTBS NCS, 2. TsCl, Pyr. 0 ºC, 84% HO O H2N Name? N CuCl2 3. KOAc, 25% Mechanism? swainsonine AcO 20% AcO CO2Et CO2Et Me OAc Kibayashi, Angew. Chem. Int. Ed. 2002, 41, 3017. OAc O BnO OAc HCO2H, Tol/THF, N serratinine OBn BOC NHBOC 0 ºC, 2 h, 88% HCO2 N Me See "Nitrogen Centered Radicals" Baran Group Meeting. Mechanism? Me Baskaran, Org. Lett. 2003, 5, 583. J. Org. Chem. 2004, 69, 3093. lepadiformine H H EtAlCl2, Kirihara, Tetrahedron. 1999, 55, 2911. NaBH 4 indolizidine 167B PIFA, TfOH, N OH N3 indolizidine 209D O MeOH, rt, 67% O 54% HO Me Mechanism? MeO2CN MeO2CN MeO2C Ma, Org. Lett. 2005, 7, 705. indolizidine 223AB N M e CO2Me CO Et CO Et 2 NH2 2 K2CO3 Overman, Tetrahedron Lett. 1988, 29, 901. + MeCN Me Cl HO Me Me Me N H HO I H2CO, CSA, H Me 80% Me MeCN, NaI, Mechanism? HN I N 100 ºC, 82% pumiliotoxin 307A pumiliotoxin 323A indolizidine 223A R Mechanism? R 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Overman, J. Am. Chem. Soc. 1984, 106, 4192. ibid. 1981, 103, 1851. Smith, Org. Lett. 2005, 7, 3247. J. Org. Chem. 2006, 71, 2547. TsN HO Me 1. H2CO Me 1, tBuLi, Et O, – 78 H HO 2 2. CSA, H S S 3 to – 45 ºC, 1 hr; 2, OTBS pumiliotoxin 251D S Me pumiliotoxin 307A 1 Me Et2O, – 78 to – 25 ºC, S TBS R HN EtOH, ! N pumiliotoxin 323A NHTs TMS 60% Me 5 hrs; 3, HMPA/Et O, 2 TBSO R O 2 – 78 to 0!ºC, 56% Me TBSO Mechanism? Overman, J. Org. Chem. 1992, 57, 1179. indolizidine 223AB Me Me HO 1. H2CO HO H H S H S H O 2. TsOH, 20% or O S 1. LHMDS, TMSCl, S Me HN N N THF, – 78 ºC N 2. LDA, TMSCl H H 3. TMSOTf, 56% H H Me 2. Grubbs 2, PhH, allopumiliotoxin 267A 65 ºC, 81% allopumiliotoxin 339B O Me O Me O Li • HO Me alkaloid 205B H 1. H Me OMe O Denmark, J. Am. Chem. Soc. 1999, 121, 3046. HN 2. TsOH N 3. HCl, 45% O OXc O N O X c , MAPh; Mechanism? t-Bu O Overman, J. Am. Chem. Soc. 1980, 102, 1454. Si !, PhH, NaHCO3 H H t-Bu O NO O MeO O 2 44% O TsOH, BnO Si MeO H OMe H H Mechanism? t-Bu N N t-Bu PhH, ! Me BnO Me 79% 1. K2OsO2(OH)4, K2CO3, Ph Ph H2O, NaHCO3, K3Fe(CN)6, 1. BnBr, CHCl3, !; NaOH AlMe tBuOH, (DHQD)2AQN 2. NaBH4 OH 2. TsCl, Pyr., 100% Ph X H H 2 c BnO BnO MAPh O OX H H Me HO O c H CH3(OEt)3 H N NBn EtO2C NBn Me 1. H2, Ran-Ni, acid, TsO ! castanospermine 160 psi, Meoh, 73% H 55% O O Si perhydrogephyrotoxin 2. HF, MeOH, 88% t-Bu t-Bu 5/10/06 Richter Indolizidine Alkaloids Baran Group Meeting Danishefsky, J. Am. Chem. Soc. 1990, 112, 2003. ibid. 1993, 115, 30. O O 1. NaBH4 2. HCl, MeOH CO2Me + O N 3. TiCl4, N PPh3 MeO2C O O TMS N2 1. Lawesson's S 2. NaOH O O N 3. NMM, N H H iBuOCOCl MeO2C 4. CH2N2, 65% Rh(OAc)2 66% SH 1. Ra-Ni, Name? MeO O Me2CO TEOCCl N N 2. Me3OBF4 H 30% H 3. NaBH Mechanism? 4 HO H 1. H2O2, O 1. mCPBA, 84% NaOH, 97% N N 2.
Load more

Recommended publications
  • Ew Routes to Indolizidine Alkaloids: the Total Synthesis of (−)Grandisine B
    ew Routes to Indolizidine Alkaloids: The Total Synthesis of (−)-Grandisine B James David Cuthbertson Thesis submitted in partial fulfilment of the requirements for the Degree of Doctor of Philosophy The University of York Department of Chemistry September 2011 Abstract The plant family Elaeocarpaceae has been the source of a plethora of structurally related alkaloids isolated over the last 50 years. This Thesis describes our synthetic approaches to (−)-grandisine B I, a bioactive indolizidine alkaloid isolated from Elaocarpus grandis in 2005. An overview of alkaloids isolated from the family Elaeocarpaceae is provided and preliminary studies into the synthesis of grandisine B I are described (Chapters 1 and 2). Novel routes to bicyclic lactams II and isoquinuclidinone frameworks III have been developed using aqueous ammonia in a one-pot amination/cyclisation sequence (Chapters 3 and 4). The scope of the developed methodology was initially demonstrated with a concise synthesis of the alkaloid (−)-mearsine V. A biomimetic synthesis of (±)- grandisine B I, using the alkaloid grandisine D IV as a synthetic precursor, is then described in Chapter 5. The development of a formic acid mediated alkyne/acetal cyclisation for the synthesis of heterocyclic scaffolds is also reported. The scope and limitations of the methodology are discussed and applications of the methodology in the synthesis of (−)-grandisine B I and structurally related Elaeocarpus alkaloids are described (Chapter 6). I Contents Abstract ...........................................................................................................................
    [Show full text]
  • Rope Parasite” the Rope Parasite Parasites: Nearly Every AuSC Child I Ever Treated Proved to Carry a Significant Parasite Burden
    Au#sm: 2015 Dietrich Klinghardt MD, PhD Infec4ons and Infestaons Chronic Infecons, Infesta#ons and ASD Infec4ons affect us in 3 ways: 1. Immune reac,on against the microbes or their metabolic products Treatment: low dose immunotherapy (LDI, LDA, EPD) 2. Effects of their secreted endo- and exotoxins and metabolic waste Treatment: colon hydrotherapy, sauna, intes4nal binders (Enterosgel, MicroSilica, chlorella, zeolite), detoxificaon with herbs and medical drugs, ac4vaon of detox pathways by solving underlying blocKages (methylaon, etc.) 3. Compe,,on for our micronutrients Treatment: decrease microbial load, consider vitamin/mineral protocol Lyme, Toxins and Epigene#cs • In 2000 I examined 10 au4s4c children with no Known history of Lyme disease (age 3-10), with the IgeneX Western Blot test – aer successful treatment. 5 children were IgM posi4ve, 3 children IgG, 2 children were negave. That is 80% of the children had clinical Lyme disease, none the history of a 4cK bite! • Why is it taking so long for au4sm-literate prac44oners to embrace the fact, that many au4s4c children have contracted Lyme or several co-infec4ons in the womb from an oVen asymptomac mother? Why not become Lyme literate also? • Infec4ons can be treated without the use of an4bio4cs, using liposomal ozonated essen4al oils, herbs, ozone, Rife devices, PEMF, colloidal silver, regular s.c injecons of artesunate, the Klinghardt co-infec4on cocKtail and more. • Symptomac infec4ons and infestaons are almost always the result of a high body burden of glyphosate, mercury and aluminum - against the bacKdrop of epigene4c injuries (epimutaons) suffered in the womb or from our ancestors( trauma, vaccine adjuvants, worK place related lead, aluminum, herbicides etc., electromagne4c radiaon exposures etc.) • Most symptoms are caused by a confused upregulated immune system (molecular mimicry) Toxins from a toxic environment enter our system through damaged boundaries and membranes (gut barrier, blood brain barrier, damaged endothelium, etc.).
    [Show full text]
  • A Review of Chemical Defense in Poison Frogs (Dendrobatidae): Ecology, Pharmacokinetics, and Autoresistance
    Chapter 21 A Review of Chemical Defense in Poison Frogs (Dendrobatidae): Ecology, Pharmacokinetics, and Autoresistance Juan C. Santos , Rebecca D. Tarvin , and Lauren A. O’Connell 21.1 Introduction Chemical defense has evolved multiple times in nearly every major group of life, from snakes and insects to bacteria and plants (Mebs 2002 ). However, among land vertebrates, chemical defenses are restricted to a few monophyletic groups (i.e., clades). Most of these are amphibians and snakes, but a few rare origins (e.g., Pitohui birds) have stimulated research on acquired chemical defenses (Dumbacher et al. 1992 ). Selective pressures that lead to defense are usually associated with an organ- ism’s limited ability to escape predation or conspicuous behaviors and phenotypes that increase detectability by predators (e.g., diurnality or mating calls) (Speed and Ruxton 2005 ). Defended organisms frequently evolve warning signals to advertise their defense, a phenomenon known as aposematism (Mappes et al. 2005 ). Warning signals such as conspicuous coloration unambiguously inform predators that there will be a substantial cost if they proceed with attack or consumption of the defended prey (Mappes et al. 2005 ). However, aposematism is likely more complex than the simple pairing of signal and defense, encompassing a series of traits (i.e., the apose- matic syndrome) that alter morphology, physiology, and behavior (Mappes and J. C. Santos (*) Department of Zoology, Biodiversity Research Centre , University of British Columbia , #4200-6270 University Blvd , Vancouver , BC , Canada , V6T 1Z4 e-mail: [email protected] R. D. Tarvin University of Texas at Austin , 2415 Speedway Stop C0990 , Austin , TX 78712 , USA e-mail: [email protected] L.
    [Show full text]
  • Contact Toxicities of Anuran Skin Alkaloids Against the Fire Ant (Solenopsis Invicta)
    Naturwissenschaften (2013) 100:185–192 DOI 10.1007/s00114-013-1010-0 ORIGINAL PAPER Contact toxicities of anuran skin alkaloids against the fire ant (Solenopsis invicta) Paul J. Weldon & Yasmin J. Cardoza & Robert K. Vander Meer & W. Clint Hoffmann & John W. Daly & Thomas F. Spande Received: 19 July 2012 /Revised: 4 January 2013 /Accepted: 7 January 2013 /Published online: 23 January 2013 # Springer-Verlag Berlin Heidelberg (outside the USA) 2013 Abstract Nearly 500 alkaloids, representing over 20 struc- estimated the cutaneous concentrations of several com- tural classes, have been identified from the skin of neotrop- pounds based on their reported recoveries from skin extracts ical poison frogs (Dendrobatidae). These cutaneous of free-ranging frogs and our measurements of the skin compounds, which are derived from arthropod prey of the surface areas of museum specimens. Pumiliotoxin 251D frogs, generally are believed to deter predators. We tested exhibited contact toxicity below its estimated cutaneous the red imported fire ant (Solenopsis invicta) for toxicosis concentration in the Ecuadorian frog, Epipedobates antho- following contact with 20 alkaloids (12 structural classes) nyi, an observation consistent with the hypothesized role identified from dendrobatids or other anurans. Individual of this compound in anuran chemical defense. Our results ants forced to contact the dried residues of 13 compounds and those of a previous study of mosquitoes indicate that exhibited convulsions and/or reduced ambulation. We some anuran skin compounds function defensively as contact toxins against arthropods, permeating their exoskeleton. Communicated by: Sven Thatje . John W. Daly deceased 5 March, 2008 Keywords Alkaloid Allomone Ant Defense Frog Toxicity P.
    [Show full text]
  • An Arthropod Source for the Pumiliotoxin Alkaloids Of
    Formicine ants: An arthropod source for the SEE COMMENTARY pumiliotoxin alkaloids of dendrobatid poison frogs Ralph A. Saporito*, H. Martin Garraffo†, Maureen A. Donnelly*, Adam L. Edwards*, John T. Longino‡, and John W. Daly†§ *Department of Biological Sciences, Florida International University, Miami, FL 33199; †Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892; and ‡Evergreen State College, Olympia, WA 98505 Contributed by John W. Daly, April 5, 2004 A remarkable diversity of bioactive lipophilic alkaloids is present in ins (1) represent alkaloid classes (Fig. 2) that share certain the skin of poison frogs and toads worldwide. Originally discov- structural features with those of known ant alkaloids, and it is ered in neotropical dendrobatid frogs, these alkaloids are now expected that they will prove to be of myrmicine ant origin as known from mantellid frogs of Madagascar, certain myobatrachid well. All of the alkaloids in frog and toad skin that appear to frogs of Australia, and certain bufonid toads of South America. originate by sequestration from myrmicine ants contain un- Presumably serving as a passive chemical defense, these alkaloids branched carbon skeletons. Coccinellid beetles appear to be a appear to be sequestered from a variety of alkaloid-containing dietary source for the coccinellines and some of the structurally arthropods. The pumiliotoxins represent a major, widespread, related tricyclic alkaloids (5). Siphonotid millipedes are the group of alkaloids that are found in virtually all anurans that are putative dietary source for the spiropyrrolizidine oximes and chemically defended by the presence of lipophilic alkaloids.
    [Show full text]
  • Sequestered Alkaloid Defenses in the Dendrobatid Poison Frog Oophaga Pumilio Provide Variable Protection from Microbial Pathogens
    John Carroll University Carroll Collected Masters Theses Theses, Essays, and Senior Honors Projects Summer 2016 SEQUESTERED ALKALOID DEFENSES IN THE DENDROBATID POISON FROG OOPHAGA PUMILIO PROVIDE VARIABLE PROTECTION FROM MICROBIAL PATHOGENS Kyle Hovey John Carroll University, [email protected] Follow this and additional works at: http://collected.jcu.edu/masterstheses Part of the Biology Commons Recommended Citation Hovey, Kyle, "SEQUESTERED ALKALOID DEFENSES IN THE DENDROBATID POISON FROG OOPHAGA PUMILIO PROVIDE VARIABLE PROTECTION FROM MICROBIAL PATHOGENS" (2016). Masters Theses. 19. http://collected.jcu.edu/masterstheses/19 This Thesis is brought to you for free and open access by the Theses, Essays, and Senior Honors Projects at Carroll Collected. It has been accepted for inclusion in Masters Theses by an authorized administrator of Carroll Collected. For more information, please contact [email protected]. SEQUESTERED ALKALOID DEFENSES IN THE DENDROBATID POISON FROG OOPHAGA PUMILIO PROVIDE VARIABLE PROTECTION FROM MICROBIAL PATHOGENS A Thesis Submitted to the Office of Graduate Studies College of Arts & Sciences of John Carroll University in Partial Fulfillment of the Requirements for the Degree of Master of Science By Kyle J. Hovey 2016 Table of Contents Abstract ................................................................................................................................1 Introduction ..........................................................................................................................3 Methods
    [Show full text]
  • Jahresbericht 2007
    Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main JAHRESBERICHT 2007 Fachbereich Medizin Fachbereich Medizin und Klinikum der Johann Wolfgang Goethe- Universität Frankfurt am Main Jahresbericht 2007 - 1- Herausgeber: Vorstand des Klinikums der Johann Wolfgang Goethe-Universität Redaktion: Dr. Barbara Pardon Theodor-Stern-Kai 7 60590 Frankfurt am Main November 2008 - 2- Inhaltsverzeichnis Organisationsstruktur des Klinikums .................................................................................. 5 Dekanat, Akademische Angelegenheiten und Selbstverwaltung ........................................ 12 Vorstand des Klinikums ...................................................................................................... 24 Verwaltung und Logistik ..................................................................................................... 42 Pflegedienstleitung .............................................................................................................. 61 Klinische, klinisch-theoretische und medizinisch-theoretische Einrichtungen Zentrum der Inneren Medizin .............................................................................................. 77 Zentrum der Chirurgie ......................................................................................................... 113 Zentrum der Frauenheilkunde und Geburtshilfe .................................................................. 135 Zentrum für Kinder- und Jugendmedizin ............................................................
    [Show full text]
  • Plant Toxins: Alkaloids and Their Toxicities
    GSC Biological and Pharmaceutical Sciences, 2019, 06(02), 021–029 Available online at GSC Online Press Directory GSC Biological and Pharmaceutical Sciences e-ISSN: 2581-3250, CODEN (USA): GBPSC2 Journal homepage: https://www.gsconlinepress.com/journals/gscbps (REVIEW ARTICLE) Plant toxins: alkaloids and their toxicities Kamarul Zaman Munirah Adibah and Mohamad Azzeme Azzreena * Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Publication history: Received on 09 January 2019; revised on 28 January 2019; accepted on 29 January 2019 Article DOI: https://doi.org/10.30574/gscbps.2019.6.2.0003 Abstract Since ancient civilization, plants have been utilized in many aspects of life, especially in medicinal purposes due to the presence of distinctive secondary metabolites like alkaloids, phenolics and terpenoids. Among them, alkaloids represent a large group of secondary metabolites that have basic properties and comprise nitrogen atom within the heterocyclic ring. Plant synthesizes alkaloids to maintain their survivability under unfavorable conditions. Over 3000 years, indigenous people have been used alkaloid-containing plant extracts to treat several ailments such as fever, snakebite and insanity. However, despite significant benefits to humans and pharmaceutical industries, some of the plant alkaloids are categorized as main plant toxins due to their enormous structural diversity and various modes of actions. Humans and animals can be exposed to
    [Show full text]
  • Evidence for an Enantioselective Pumiliotoxin 7-Hydroxylase in Dendrobatid Poison Frogs of the Genus Dendrobates
    Evidence for an enantioselective pumiliotoxin 7-hydroxylase in dendrobatid poison frogs of the genus Dendrobates John W. Daly*†, H. Martin Garraffo*, Thomas F. Spande*, Valerie C. Clark*‡, Jingyuan Ma*§, Herman Ziffer*¶, and John F. Cover, Jr.ʈ *Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-0820; and ʈNational Aquarium in Baltimore, 501 East Pratt Steet, Baltimore, MD 21202 Contributed by John W. Daly, July 15, 2003 Dendrobatid poison frogs readily accumulate alkaloids from diet dophryne frogs seemed dependent on diet for their PTXs͞aPTXs into skin, where such compounds serve as a chemical defense (15). However, raised in captivity, the Pseudophryne frogs still against predators. Arthropods seem to be the source of decahyd- contained pseudophrynamines in skin and, thus, the frogs seem roquinolines (DHQs), several izidines, coccinellines, spiropyrroliz- able to synthesize these unusual indolic alkaloids (15). The idines, pumiliotoxins (PTXs), and allopumiliotoxins (aPTXs). A DHQ dietary source of the many classes of alkaloids found in skin of .iso-223F, and PTX (؉)-251D were fed to poison frogs of the frog taxa has become a major challenge dendrobatid genera Dendrobates, Epipedobates, and Phyllobates. In the present alkaloid-feeding experiments, a synthetic DHQ The two alkaloids were accumulated in skin unchanged except for iso-223F, an isomer of a natural DHQ, code name 223F (3), was the three species of Dendrobates, where Ϸ80% of accumulated fed along with a simple PTX (ϩ)-251D. DHQs were known to PTX (؉)-251D was stereoselectively hydroxylated to aPTX (؉)- be readily accumulated unchanged into skin of dendrobatid frogs 267A.
    [Show full text]
  • Geographic and Seasonal Variation in Alkaloid-Based Chemical Defenses of Dendrobates Pumilio from Bocas Del Toro, Panama
    J Chem Ecol (2006) 32: 795–814 DOI 10.1007/s10886-006-9034-y Geographic and Seasonal Variation in Alkaloid-Based Chemical Defenses of Dendrobates pumilio from Bocas del Toro, Panama Ralph A. Saporito & Maureen A. Donnelly & H. Martin Garraffo & Thomas F. Spande & John W. Daly Received: 11 November 2005 /Revised: 15 December 2005 / Accepted: 3 January 2006 / Published online: 5 May 2006 # Springer Science + Business Media, Inc. 2006 Abstract Poison frogs contain an alkaloid-based chemical defense that is derived from a diet of certain alkaloid-containing arthropods, which include mites, ants, beetles, and millipedes. Variation in population-level alkaloid profiles among species has been documented, and more than 800 different alkaloids have been identified. In the present study, we examine individual alkaloid variation in the dendrobatid poison frog Dendrobates pumilio among seven populations and between two seasons on Isla Bastimentos, located in the Bocas del Toro archipelago of Panama. Alkaloid profiles vary among populations and between seasons, illustrating that chemical defense in this species can vary on a small spatial and temporal scale. Alkaloid variation among populations is marginally correlated with geographic distance, and close populations have profiles more similar to each other than to distant populations. Individuals within populations also vary in alkaloid profiles. Differences are attributed to both spatial and temporal variations in the availability of alkaloid-containing arthropods. Many of the alkaloids present in the skin of D. pumilio appear likely to be of ant origin, supporting the importance of myrmecophagy in chemical defense among poison frogs. However, a variety of frog skin alkaloids was recently detected in mites, suggesting that mites may also play an important role in chemical defense.
    [Show full text]
  • Canthariphile Insekten 2 Canthariphile Feuerkäfer Der Gattung Schizotus Nehmen Das Toxische Cantharidin Aus Schenkelböcken Auf
    Canthariphile Insekten 2 canthariphile Feuerkäfer der Gattung Schizotus nehmen das toxische Cantharidin aus Schenkelböcken auf. Das Gift wird ge- speichert und ggf. an Weibchen und Nachkommenschaft weiter- gereicht O O CH3 O CH 3 O Cantharidintransfer Aufnahme von Cantharidin in die Anhangsdrüsen und Männchen von Neopyrochroa Kopfgruben des Männchens (links). Bei der Balz beißt das spec. bei der Aufnahme von Weibchen (rechts) in die Kopfgruben des Männchens und Cantharidin überprüft dessen Cantharidingehalt. Das Weibchen legt cantharidinhaltige Eier ab. Der Bei der Kopula wird Cantharidin aus den chemische Schutz der Eier wird gewährleistet durch männlichen Anhangsdrüsen in die weiblichen das "Hochzeitsgeschenk" des Männchens in Form Geschlechtsorgane (Bursa) transferiert. von Cantharidin Balz bei Neopyrochroa spec. Weibchen (rechts) beißt in die Kopfgruben des Männchens Nach der Kopula wehrt das Weibchen Kopula (rechts) andere kopulations- bereite Männchen ab. Kopfgruben Männchen von des Neopyrochroa Männchens frisst an kristallinem Cantharidin Cantharidin- kristalle aus der Aus den Kopfgruben Kopfgrube eine der Männchen wird mit Männchens einer Nadel das fadenziehende Sekret gewonnen Toxin LD 50 (µg/kg) Molmasse Chemie Primärwirkung Bakterien-Toxin: Botulinum-Toxin (Clostridium botulinum) 0,00026 150 000 Peptidtoxin Lebensmittelvergiftungen Palytoxin, Toxin der Krustenanemone 0,15 2 300 Polyketid bildet Poren in Zellmembran (Palythoa spp.) Cantharidin (aus Ölkäfern u. Schenkelböcken) 1,0 196 Terpenanhydrid PP2A – Hemmer Froschtoxin: Batrachotoxin 2 538 Steroidalkaloid vermindert Inaktivierung (Phyllobates tricolor ) Na +-Kanäle Fischtoxin: Tetrodotoxin 9 319 Chinazolinan- Blockade Na +-Kanäle hydrid Muscheltoxin: Saxitoxin 9 281 Purinalkaloid Blockade Na +-Einstrom Skorpiontoxin (Androctonus australis ) 17 6 800 Peptidtoxin Wirkung auf Na +-Kanäle Schlangengift-Toxine: Taipoxin (aus 2 42 000 Polypeptid Neurotoxin: Atemlähmung, Herz- dem Gift des australischen Taipans aus 3 Unter- versagen, Kreislaufversagen Oxyuranus scutellatus ) einh.
    [Show full text]
  • Transcriptomic Signatures of Experimental Alkaloid Consumption in a Poison Frog
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Digitale Bibliothek Braunschweig G C A T T A C G G C A T genes Article Transcriptomic Signatures of Experimental Alkaloid Consumption in a Poison Frog Eugenia Sanchez 1,2,* , Ariel Rodríguez 3 , Jose H. Grau 4, Stefan Lötters 5, Sven Künzel 6, 7 8,9 10 11, Ralph A. Saporito , Eva Ringler , Stefan Schulz , Katharina C. Wollenberg Valero y 1, and Miguel Vences y 1 Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany; [email protected] 2 Department of Biology, Stanford University, Stanford, CA 94305, USA 3 Institut fur Zoologie, Tierärztliche Hochschule Hannover, 30559 Hannover, Germany; [email protected] 4 Museum für Naturkunde Berlin, Leibniz-Institut für Evolutions- und Biodiversitätsforschung, 10115 Berlin, Germany; [email protected] 5 Biogeography Department, Trier University, 54296 Trier, Germany; [email protected] 6 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany; [email protected] 7 Department of Biology, John Carroll University, University Heights, OH 44118, USA; [email protected] 8 Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna, and University of Vienna, A-1210 Vienna, Austria; [email protected] 9 Department of Integrative Zoology, University of Vienna, A-1090 Vienna, Austria 10 Institute of Organic Chemistry, Technische Universität Braunschweig, 38106 Braunschweig, Germany; [email protected] 11 Department of Biological and Marine Sciences, University of Hull, Kingston-Upon Hull 01482, UK; [email protected] * Correspondence: [email protected] These authors contributed equally to the manuscript.
    [Show full text]