Academic Press is an imprint of Elsevier 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, USA 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 125 London Wall, London EC2Y 5AS, UK The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First edition 2016 Copyright © 2016 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein ISBN: 978-0-12-803434-7 ISSN: 1099-4831 For information on all Academic Press publications visit our website at http://store.elsevier.com/ CONTRIBUTORS Joseph P Michael Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg, Gauteng, South Africa vii j PREFACE Since the appearance of its first volume in 1950, the book series The Alkaloids has become the leading publication forum for alkaloid chemistry The present book is the 75th volume and thus represents a jubilee for The Alkaloids In the long history of this series, single-topic volumes have been very rare: Volume 25, published in 1985, described “Antitumor Alkaloids”; Volume 37, published in 1990, compiled “Bisindole Alkaloids from Catharanthus roseus (L.)”; Volume 65, published in 2008, reviewed the “Chemistry and Biology of Carbazole Alkaloids”; and in 2010, Volume 69 summarized “The C19-Diterpenoid Alkaloids.” Volume 75 represents another singlechapter volume and is dedicated to “Simple Indolizidine and Quinolizidine Alkaloids.” The author, Joseph P Michael from the Molecular Sciences Institute at the University of the Witwatersrand in South Africa, had already written two of the three previous reviews on this topic for The Alkaloids In Chapter of Volume 28, published in 1986, Arthur S Howard and Joseph P Michael presented the first full coverage of “Simple Indolizidine and Quinolizidine Alkaloids” within this series In Chapter of Volume 44, published in 1993, Hiroki Takahata and Takefumi Momose gave an update on “Simple Indolizidine Alkaloids” In Chapter of Volume 46, published in 1995, David J Robins described the “Biosynthesis of Pyrrolizidine and Quinolizidine Alkaloids” The last overview on “Simple Indolizidine and Quinolizidine Alkaloids” in this series was compiled again by Joseph P Michael and published in 2001 as Chapter of Volume 55 Thus, there could have been no better expert for the present review which is covering the tremendous development in this field from the middle of 1999 till the end of 2013 This view of the editor has been confirmed by Jo Michael’s remarkably extensive compilation of exceptional quality Hans-Joachim Kn€ olker Technische Universit€at Dresden, Dresden, Germany ix j CHAPTER ONE Simple Indolizidine and Quinolizidine Alkaloids Joseph P Michael Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg, Gauteng, South Africa E-mail: joseph.michael@wits.ac.za Contents Introduction Indolizidine Alkaloids from Fungal and Microbial Sources 2.1 Slaframine 2.2 Cyclizidine and JBIR-102 2.3 Streptomyces Metabolites 2.4 Pantocins A and A2 Hydroxylated Indolizidine Alkaloids 3.1 General Reviews 3.2 1-Hydroxyindolizidines 3.3 Lentiginosine and Related Compounds 5 12 15 16 19 19 21 26 3.3.1 Isolation and Biological Activity 3.3.2 Synthesis 28 28 3.4 Steviamine 3.5 Swainsonine 64 69 3.5.1 Occurrence, Isolation, and Characterization 3.5.2 Synthesis 3.5.3 Biological Activity 69 73 116 3.6 Castanospermine and Related Compounds 122 3.6.1 Isolation and Structure 3.6.2 Synthesis 3.6.3 Biological Activity 122 123 140 3.7 The Putative Uniflorines Plant Indolizidine and Quinolizidine Alkaloids Bearing Alkyl, Functionalized Alkyl, or Alkenyl Substituents 4.1 Dendroprimine 4.2 Prosopis Alkaloids 4.3 5,6,7,8-Tetrahydroindolizine Alkaloids 4.4 Anibamine The Alkaloids, Volume 75 ISSN 1099-4831 http://dx.doi.org/10.1016/bs.alkal.2014.12.001 © 2016 Elsevier Inc All rights reserved 146 148 148 153 159 162 j Joseph P Michael 4.5 Elaeocarpus Alkaloids 4.5.1 Isolation and Characterization 4.5.2 Biogenesis 4.5.3 Synthesis 4.6 Lupin Alkaloids 4.6.1 Occurrence and Characterization 4.6.2 Structural Investigations 4.6.3 Synthesis 4.7 Myrtine and Epimyrtine 4.8 Lycopodium Alkaloids 4.8.1 Isolation and Characterization 4.8.2 Synthesis 4.9 Porantheridine 4.10 Plumerinine Plant Indolizidine and Quinolizidine Alkaloids Bearing Aryl or Heteroaryl Substituents 5.1 Ipalbidine and Related Alkaloids 5.1.1 Isolation and Characterization 5.1.2 Synthesis 5.2 Septicine, Julandine, and Related Alkaloids 5.2.1 Isolation, Characterization, and Biological Properties 5.2.2 Synthesis 5.3 Ficuseptine 5.4 Lythraceae Alkaloids 5.4.1 Isolation and Characterization 5.4.2 Synthesis 5.5 Nuphar Alkaloids 5.5.1 Isolation and Biological Activity 5.5.2 Syntheses of Nuphar Quinolizidines 5.5.3 Syntheses of the Nuphar Indolizidine 5.6 QuinolizidineeQuinazoline Alkaloids Indolizidine and Quinolizidine Alkaloids from Terrestrial Animals 6.1 Indolizidine and Quinolizidine Alkaloids from Arthropods 6.1.1 6.1.2 6.1.3 6.1.4 Isolation and Characterization Monomorine I Solenopsis Alkaloids (3S,5R,8S,8aS)-3-Butyl-5-Propyl-8-Hydroxyindolizine 6.2 Indolizidine and Quinolizidine Alkaloids from Amphibians 6.2.1 6.2.2 6.2.3 6.2.4 6.2.5 Occurrence: The “Dietary Hypothesis” Isolation and Characterization 5-Alkylindolizidines 3,5-Disubstituted Indolizidine Alkaloids 5,8-Disubstituted Indolizidine Alkaloids 165 165 169 169 179 179 181 184 207 215 215 216 221 229 229 229 229 230 235 237 238 247 248 248 250 275 275 276 280 283 286 286 286 292 309 312 314 315 319 325 326 344 Simple Indolizidine and Quinolizidine Alkaloids 6.2.6 6.2.7 6.2.8 6.2.9 6.2.10 6.2.11 6.2.12 5,6,8-Trisubstituted Indolizidine Alkaloids Epiquinamide 1,4-Disubstituted Quinolizidine Alkaloids 4,6-Disubstituted Quinolizidine Alkaloids Pumiliotoxins and Allopumiliotoxins Homopumiliotoxins Biological Activity Indolizidine and Quinolizidine Alkaloids from Marine Sources 7.1 Clathryimines and Callyimine A 7.2 Stellettamides 7.3 Piclavines 7.4 Clavepictines and Pictamine 7.5 Bis(quinolizidine) Alkaloids References 374 384 406 420 424 442 447 451 451 452 456 460 465 468 INTRODUCTION It has been over 13 years since the simple indolizidine and quinolizidine alkaloids were surveyed in Volume 55 of this treatise.1 That survey, which updated prior coverage of the indolizidine alkaloids in Volume 44,2 and of both indolizidine and quinolizidine alkaloids in Volume 28,3 aimed for comprehensive treatment up to the middle of 1999 This review covers publications from mid-1999 to the end of 2013 Once again it is necessary to emphasize that the concept of a “simple” izidine alkaloid is subjective Because the indolizidine and quinolizidine motifs are so widely distributed in natural products, some limitations have had to be imposed in order to keep the chapter to a manageable length Thus, with very few exceptions, only those alkaloids that possess an isolated azabicyclic nucleusdi.e., one not embedded within a fused polycyclic assemblagedare considered The numbering systems for the two motifs are shown in Figure In general, the IUPAC numbering system for the parent octahydroindolizine (1) and octahydro-2H-quinolizine (2) ring systems is used Some authors also label the bridgehead positions 8a and 9a as and 10, respectively One also occasionally encounters indolizidines and quinolizidines with the 1-azabicyclo[4.3.0]nonane (3) or 1-azabicyclo[4.4.0] decane (4) numbering systems, respectively Joseph P Michael Figure Alternative numbering systems for the indolizidine and quinolizidine ring systems The two classes of alkaloids are of such widespread occurrence in living systems that the organization of the voluminous material in this chapter presents some problems Relevant alkaloids have been isolated from microorganisms and fungi, higher plants, and both terrestrial and marine animals For convenience, these broad categories are used in the presentation of the subject matter In addition, since alkaloids from higher plants constitute the majority of compounds of interest, they are further categorized according to the substituents on the bicyclic core In view of the diversity of the families and genera in which the alkaloids are found, it is a little surprising that so few have merited chapters of their own in this series of reviews in the intervening years References to these chapters are provided in the appropriate sections Several other general reviews dealing with aspects of indolizidine and quinolizidine alkaloid chemistry were published during the period under consideration The series of annual reports in the Royal Society of Chemistry’s journal Natural Product Reports, which provided regular coverage of both simple and various more complex indolizidine and quinolizidine alkaloids, ended in 2008.4e11 Another important review that dealt principally with pertinent alkaloids from ants and amphibians, slaframine, polyhydroxylated indolizidine alkaloids, and the lupin quinolizidine alkaloids was published in the series Studies in Natural Product Chemistry in 2002, and covered the period 1994 to 1999.12 Simple Indolizidine and Quinolizidine Alkaloids As is to have been expected, a substantial portion of this chapter is devoted to total synthesis A number of useful reviews describing general strategies for the synthesis of alkaloids, among them radical cyclizations,13 asymmetric aza-Michael reactions,14 and palladium-mediated total syntheses,15 include examples of simple indolizidine and quinolizidine alkaloid targets Also valuable are the overviews from individual research groups on their own approaches to the construction of nitrogen heterocycles, with examples illustrating applications to alkaloid synthesis in general and izidines in particular These include Jefford’s use of pyrroles derived from a-amino acids as building blocks for various indolizidines16; the CN(R,S) method of Husson and Royer based on the use of chiral non-racemic N-cyanomethyloxazolidines as masked iminium ion intermediates17; the numerous contributions of Toyooka and Nemoto to the syntheses of marine and amphibian alkaloids18,19; allylsilaneeN-acyliminium ion cyclizations as exploited by Remuson for the synthesis of a wide variety of relevant alkaloids20; Mori’s approach to the use of molecular nitrogen as the nitrogen source in alkaloid synthesis21; Martin’s applications of imines as key intermediates in Mannich and related reactions22; and developments by Rovis and others of multicomponent cycloadditions for the catalytic asymmetric synthesis of alkaloidal targets.23 Other surveys of specific classes of alkaloids are highlighted in the appropriate sections As will becomes apparent in subsequent sections, synthetic strategies that use metathesis, especially ring-closing metathesis, have assumed prominence during the period covered by this review Ruthenium-containing catalysts are especially important Since they are mentioned repeatedly in the ensuing discussion, the most widely used catalysts are illustrated in Figure They include the Grubbs first- and second-generation catalysts (5) and (6), the HoveydaeGrubbs catalyst (7), and the GrubbseNolan catalyst (8).24 INDOLIZIDINE ALKALOIDS FROM FUNGAL AND MICROBIAL SOURCES 2.1 Slaframine The parasympathomimetic slaframine (9), isolated from the fungus Rhizoctonia leguminicola, received little attention in the primary literature during the review period Four asymmetric total syntheses were reported, the earliest of them by Comins and Fulp, who made use of the recyclable Joseph P Michael Figure Metathesis catalysts: Grubbs first-generation catalyst (5), Grubbs secondgeneration catalyst (6), HoveydaeGrubbs catalyst (7), and GrubbseNolan catalyst (8) auxiliary (À)-trans-2-(a-cumyl)cyclohexanol (10) to control the absolute configuration at the alkaloid’s C-8a site (Scheme 1).25 Reaction between 4-methoxy-3-(triisopropylsilyl)pyridine (11) and the chloroformate of the auxiliary produced the N-acylpyridinium salt, to which was added the mixed 1-propenylcuprate 12 The reaction proceeded in only 87% diastereomeric excess (de), but the chiral dihydropyridone intermediate 13 could be isolated in 61% yield after radial preparative layer chromatography After several functional group transformations to the vinyl triflate 14, the stereogenic center at C-1 was introduced by intramolecular phenylselenocarbamation, which yielded the bicyclic oxazolidinone 15 as the only diastereomer Further functional group manipulations, including a problematic chemoselective defunctionalization of the vinyl triflate, provided 16, basic hydrolysis and decarboxylation of which led to formation of the indolizidine skeleton by in situ cyclization The bicyclic product was isolated as the acetate 17, which has the requisite absolute configurations at both C-1 and C-8a As a prelude to introducing the final stereogenic center at C-6, the difficult transformation of vinyl bromide 17 into the vinyl acetate 18 required heating with freshly prepared copper(I) acetate in N-methylpyrrolidone (NMP) at 202 C for 14 h The product, formed in 66% yield, was converted directly into oxime 19, a known intermediate in previous syntheses of (À)-slaframine.26,27 When the authors repeated the reported hydrogenation of the oxime over platinum dioxide, however, a mixture of Simple Indolizidine and Quinolizidine Alkaloids Scheme Synthesis of (À)-slaframine (9) and (À)-N-acetylslaframine (20) by Comins and Fulp.25 Reagents and conditions: (a) ClCO2-()-TCC; (b) cuprate 12; (c) H3Oỵ, then chromatography; (d) NaOMe, MeOH, heat; (e) HCl (6 M); (f) n-BuLi; (g) CbzCl; (h) NBS, CH2Cl2; (i) L-Selectride; (j) 2-N(Tf)2-5-Cl-py; (k) PhSeCl, MeCN; (l) H2O2, THF; (m) (C6H11)2BH; (n) NaBO3; (o) Pd(OAc)2 (10%), dppf (10%), Et3SiH, NEt3; (p) NCS, Ph3P, CH2Cl2,À35 C to rt; (q) Ac2O, py; (r) CuOAc (10 equiv.), NMP, 202 C, 14 h; (s) NH2OH$HCl (4.5 equiv.), EtOH, py, 80 C; (t) H2 (40 psi), PtO2, aq HCl, h (À)-slaframine (9) and its O-deacetyl analog was obtained Acetylation of this crude mixture yielded (À)-N-acetylslaframine 20 in 20% overall yield based on oxime 19 An unusual synthesis of (À)-slaframine (9) by Greene and coworkers proceeds via a cyclobutanone formed in a [2 ỵ 2] ketene cycloaddition in which (R)-(ỵ)-1-(2,4,6-triisopropylphenyl)ethanol 21 functions as a chiral auxiliary (Scheme 2).28 This alcohol was incorporated into the dichloro 502 Cumulative Index of Titles Catharanthus alkaloids, 59, 281 (2002) Catharanthus roseus, biosynthesis of terpenoid indole alkaloids in, 49, 222 (1997) Celastraceae alkaloids, 16, 215 (1977) Cephalostatins and Ritterazines, 72, 153 (2013) Cephalotaxus alkaloids, 23, 157 (1984), 51, 199 (1998) Cevane group of Veratrum alkaloids, 41, 177 (1992) Chemistry of hapalindoles, fischerindoles, ambiguines, and welwitindolinones, 73, 65 (2014) Chemosystematics of alkaloids, 50, 537 (1998) Chemotaxonomy of Papaveraceae and Fumariaceae, 29, (1986) Chinese medicinal plants, alkaloids from, 32, 241 (1988) Chirality transmission by alkaloids, 53, (2000) Chromone alkaloids, 31, 67 (1987) Cinchona alkaloids, 3, (1953), 14, 181 (1973), 34, 332 (1988) Colchicine, 2, 261 (1952), 6, 247 (1960), 11, 407 (1968), 23, (1984) pharmacology and therapeutic aspects of, 53, 287 (2000) Colchicum alkaloids and allo congeners, 41, 125 (1992) Configuration and conformation, elucidation by X-ray diffraction, 22, 51 (1983) Corynantheine, yohimbine, and related alkaloids, 27, 131 (1986) Cularine alkaloids, 4, 249 (1954), 10, 463 (1967), 29, 287 (1986) Curare-like effects, 5, 259 (1955) Cyclic tautomers of tryptamine and tryptophan, 34, (1988) Cyclopeptide alkaloids, 15, 165 (1975), 67, 79 (2009) Cylindrospermopsin alkaloids, 70, (2011) Cytotoxic alkaloids, modes of action, 64, (2007) D Daphniphyllum alkaloids, 15, 41 (1975), 29, 265 (1986), 60, 165 (2003) Delphinium alkaloids, 4, 275 (1954), 7, 473 (1960) C10-diterpenes, 12, (1970) C20-diterpenes, 12, 136 (1970) Detection of through IR and Raman spectroscopy, 67, 217 (2009) Dibenzazonine alkaloids, 35, 177 (1989) Dibenzopyrrocoline alkaloids, 31, 101 (1987) Diplorrhyncus alkaloids, 8, 336 (1965) Diterpenoid alkaloids Aconitum, 7, 473 (1960), 12, (1970), 12, 136 (1970), 34, 95 (1988) C18, 67, (2009) C19, 69, (2010) C20, 59, (2002) chemistry, 18, 99 (1981), 42, 151 (1992) Delphinium, 7, 473 (1960), 12, (1970), 12, 136 (1970) Garrya, 7, 473 (1960), 12, (1960), 12, 136 (1970) general introduction, 12, xv (1970) structure, 17, (1979) synthesis, 17, (1979) Duguetia alkaloids, 68, 83 (2010) Cumulative Index of Titles 503 E Eburnamine-vincamine alkaloids, 8, 250 (1965), 11, 125 (1968), 20, 297 (1981), 42, (1992) Ecological activity of alkaloids, 47, 227 (1995) Elaeocarpus alkaloids, 6, 325 (1960) Ellipticine and related alkaloids, 39, 239 (1990), 57, 235 (2001) Enamide cyclizations in alkaloid synthesis, 22, 189 (1983) Enzymatic transformation of alkaloids, microbial and in vitro, 18, 323 (1981) Ephedra alkaloids, 3, 339 (1953) Epibatidine, 46, 95 (1995) Ergot alkaloids, 8, 726 (1965), 15, (1975), 38, (1990), 50, 171 (1998), 54, 191 (2000), 63, 45 (2006) Erythrina alkaloids, 2, 499 (1952), 7, 201 (1960), 9, 483 (1967), 18, (1981), 48, 249 (1996), 68, 39 (2010) Erythrophleum alkaloids, 4, 265 (1954), 10, 287 (1967) Eupomatia alkaloids, 24, (1985) F Forensic chemistry, alkaloids, 12, 514 (1970) by chromatographic methods, 32, (1988) G Galanthamine history and introduction, 68, 157 (2010) production, 68, 167 (2010) Galanthus Galbulimima alkaloids, 9, 529 (1967), 13, 227 (1971) Gardneria alkaloids, 36, (1989) Garrya alkaloids, 7, 473 (1960), 12, (1970), 12, 136 (1970) Geissospermum alkaloids, 8, 679 (1965) Gelsemium alkaloids, 8, 93 (1965), 33, 84 (1988), 49, (1997) Glycosides, monoterpene alkaloids, 17, 545 (1979) Guatteria alkaloids, 35, (1989) H Halogenated alkaloids biosynthesis of, 71, 167 (2012) occurrence of, 71, (2012) Haplophyton cimicidum alkaloids, 8, 673 (1965) Hasubanan alkaloids, 16, 393 (1977), 33, 307 (1988) Hasubanan and acutumine alkaloids, 73, 161 (2014) Hernandiaceae alkaloids, 62, 175 (2005) Histochemistry of alkaloids, 39, 165 (1990) Holarrhena group, steroid alkaloids, 7, 319 (1960) Homalium alkaloids: isolation, synthesis and absolute configuration assignment, 74, 121 (2015) Hunteria alkaloids, 8, 250 (1965) 504 I Cumulative Index of Titles Iboga alkaloids, 8, 203 (1965), 11, 79 (1968), 59, 281 (2002) Ibogaine alkaloids addict self-help, 56, 283 (2001) as a glutamate antagonist, 56, 55 (2001) comparative neuropharmacology, 56, 79 (2001) contemporary history of, 56, 249 (2001) drug discrimination studies with, 56, 63 (2001) effects of rewarding drugs, 56, 211 (2001) gene expression, changes in, 56, 135 (2001) mechanisms of action, 56, 39 (2001) multiple sites of action, 56, 115 (2001) neurotoxicity assessment, 56, 193 (2001) pharmacology of, 52, 197 (1999) review, 56, (2001) treatment case studies, 56, 293 (2001) use in equatorial African ritual context, 56, 235 (2001) Imidazole alkaloids, 3, 201 (1953), 22, 281 (1983) Indole alkaloids, 2, 369 (1952), 7, (1960), 26, (1985) ajmaline group of, 55, (2001) biomimetic synthesis of, 50, 415 (1998) biosynthesis in Catharanthus roseus, 49, 222 (1997) biosynthesis in Rauvolfia serpentina, 47, 116 (1995) distribution in plants, 11, (1968) Reissert synthesis of, 31, (1987) sarpagine group of, 52, 103 (1999) simple, 10, 491 (1967), 26, (1985) Indole diterpenoid alkaloids, 60, 51 (2003) Indolizidine alkaloids, 28, 183 (1986), 44, 189 (1993), 55, 91 (2001), 75, (2016) 2,2’-Indolylquinuclidine alkaloids, chemistry, 8, 238 (1965), 11, 73 (1968) Infrared spectroscopy of alkaloids, 67, 217 (2009) In vitro and microbial enzymatic transformation of alkaloids, 18, 323 (1981) Ipecac alkaloids, 3, 363 (1953), 7, 419 (1960), 13, 189 (1971), 22, (1983), 51, 271 (1998) Isolation of alkaloids, 1, (1950) Isoquinoline alkaloids, 7, 423 (1960) biosynthesis, 4, (1954) 13C-NMR spectra, 18, 217 (1981) Reissert synthesis of, 31, (1987) simple isoquinoline alkaloids 4, (1954), 21, 255 (1983) Isoquinolinequinones, 21, 55 (1983), 53, 120 (2000) Isoxazole alkaloids, 57, 186 (2001) K Khat (Catha edulis) alkaloids, 39, 139 (1990) Kopsia alkaloids, 8, 336 (1965), 66, (2008) Cumulative Index of Titles 505 L Lead tetraacetate oxidation in alkaloid synthesis, 36, 70 (1989) Local anesthetics, 5, 211 (1955) Localization in the plant, 1, 15 (1950), 6, (1960) Lupine alkaloids, 3, 119 (1953), 7, 253 (1960), 9, 175 (1967), 31, 116 (1987), 47, (1995) Lycopodium alkaloids, 5, 295 (1955), 7, 505 (1960), 10, 305 (1968), 14, 347 (1973), 26, 241 (1985), 45, 233 (1994), 61, (2005), 72, (2013) Lythraceae alkaloids, 18, 263 (1981), 35, 155 (1989) M Macrocyclic peptide alkaloids from plants, 26, 299 (1985), 49, 301 (1997) Madangamine group alkaloids, 74, 159 (2015) Mammalian alkaloids, 21, 329 (1983), 43, 119 (1993) Manske, R.H.F., biography of, 50, (1998) Manzamine alkaloids, 60, 207 (2003) Marine alkaloids, 24, 25 (1985), 41, 41 (1992), 52, 233 (1999) bromotyrosine alkaloids, 61, 79 (2005) Marine bacteria, alkaloids from, 53, 120 (2000) Marine bi-, bis-, and trisindole alkaloids, 73, (2014) Maytansinoids, 23, 71 (1984) Melanins, 36, 254 (1989) chemical and biological aspects, 60, 345 (2003) Melodinus alkaloids, 11, 205 (1968) Mesembrine alkaloids, 9, 467 (1967) Metabolic transformation of alkaloids, 27, 323 (1986) Microbial and in vitro enzymatic transformation of alkaloids, 18, 323 (1981) Mitragyna alkaloids, 8, 59 (1965), 10, 521 (1967), 14, 123 (1973) Molecular modes of action of cytotoxic alkaloids, 64, (2007) Monoterpene alkaloids, 16, 431 (1977), 52, 261 (1999) glycosides, 17, 545 (1979) Morphine alkaloids, 2, (part 1), 161 (part 2) (1952), 6, 219 (1960), 13, (1971), 45, 127 (1994) Muscarine alkaloids, 23, 327 (1984) Mushrooms, alkaloids from, 40, 190 (1991) Mydriatic alkaloids, 5, 243 (1955) N a-Naphthophenanthridine alkaloids, 4, 253 (1954), 10, 485 (1967) Naphthylisoquinoline alkaloids, 29, 141 (1986), 46, 127 (1995) Narcotics, 5, (1955) Narcissus alkaloids, 63, 87 (2006) New Caledonia, alkaloids from the medicinal plants of, 48, (1996) Nitrogen-containing metabolites from marine bacteria, 53, 239, (2000), 57, 75 (2001) Non-iridoid bisindole alkaloids, 47, 173 (1995) Nuclear magnetic resonance imaging, C19 diterpenes, 69, 381–419 (2010) Nuphar alkaloids, 9, 441 (1967), 16, 181 (1977), 35, 215 (1989) 506 Cumulative Index of Titles O Ochrosia alkaloids, 8, 336 (1965), 11, 205 (1968) Ourouparia alkaloids, 8, 59 (1965), 10, 521 (1967) Oxazole alkaloids, 35, 259 (1989) Oxindole alkaloids, 14, 83 (1973) Oxoaporphine alkaloids, 14, 225 (1973) P Pancratium alkaloids, 68, (2010) Pandanus alkaloids chemistry and biology, 66, 215 (2008) Papaveraceae alkaloids, 10, 467 (1967), 12, 333 (1970), 17, 385 (1979) pharmacology, 15, 207 (1975) toxicology, 15, 207 (1975) Pauridiantha alkaloids, 30, 223 (1987) Pavine and isopavine alkaloids, 31, 317 (1987) Pentaceras alkaloids, 8, 250 (1965) Peptide alkaloids, 26, 299 (1985), 49, 301 (1997) Phenanthrene alkaloids, 39, 99 (1990) Phenanthroindolizidine alkaloids, 19, 193 (1981) Phenanthroquinolizidine alkaloids, 19, 193 (1981) b-Phenethylamines, 3, 313 (1953), 35, 77 (1989) Phenethylisoquinoline alkaloids, 14, 265 (1973), 36, 172 (1989) Phthalideisoquinoline alkaloids, 4, 167 (1954), 7, 433 (1960), 9, 117 (1967), 24, 253 (1985) Picralima alkaloids, 8, 119 (1965), 10, 501 (1967), 14, 157 (1973) Piperidine alkaloids, 26, 89 (1985) Plant biotechnology, for alkaloid production, 40, (1991), 50, 453 (1998) Plant systematics, 16, (1977) Pleiocarpa alkaloids, 8, 336 (1965), 11, 205 (1968) Polyamine alkaloids, 22, 85 (1983), 45, (1994), 50, 219 (1998), 58, 83 (2002) analytical aspects of, 58, 206 (2002) biogenetic aspects of, 58, 274 (2002) biological and pharmacological aspects of, 46, 63 (1995), 58, 281 (2002) catalog of, 58, 89 (2002) synthesis of cores of, 58, 243 (2002) Polyhalogenated alkaloids in environmental and food samples, 71, 211 (2012) Pressor alkaloids, 5, 229 (1955) Protoberberine alkaloids, 4, 77 (1954), 9, 41 (1967), 28, 95 (1986), 62, (2005) biotransformation of, 46, 273 (1955) transformation reactions of, 33, 141 (1988) Protopine alkaloids, 4, 147 (1954), 34, 181 (1988) Pseudocinchoma alkaloids, 8, 694 (1965) Pseudodistomins, 50, 317 (1998) Purine alkaloids, 38, 226 (1990) Putrescine and related polyamine alkaloids, 58, 83 (2002) Pyridine alkaloids, 1, 165 (1950), 6, 123 (1960), 11, 459 (1968), 26, 89 (1985) Cumulative Index of Titles 507 Pyrrolidine alkaloids, 1, 91 (1950), 6, 31 (1960), 27, 270 (1986) Pyrrolizidine alkaloids, 1, 107 (1950), 6, 35 (1960), 12, 246 (1970), 26, 327 (1985) biosynthesis of, 46, (1995) Pyrrolo[2,1-a] isoquinoline alkaloids synthesis of 70, 79 (2011) Q Quinazolidine alkaloids, see Indolizidine alkaloids Quinazoline alkaloids, 3, 101 (1953), 7, 247 (1960), 29, 99 (1986) Quinazolinocarbolines, 8, 55 (1965), 21, 29 (1983) Quinoline alkaloids related to anthranilic acid, 3, 65 (1953), 7, 229 (1960), 17, 105 (1979), 32, 341 (1988) Quinolinequinone alkaloids, 49, 79 (1997) Quinolinequinoneimine alkaloids, 49, 79 (1977) Quinolizidine alkaloids, 28, 183 (1986), 55, 91 (2001), 75, (2016) biosynthesis of, 47, (1995) R Raman spectroscopy of alkaloids, 67, 217 (2009) Rauwolfia alkaloids, 8, 287 (1965) biosynthesis of, 47, 116 (1995) Recent studies on the synthesis of strychnine, 64, 103 (2007) Regulation of alkaloid biosynthesis in plants, 63, (2006) Reissert synthesis of isoquinoline and indole alkaloids, 31, (1987) Reserpine, chemistry, 8, 287 (1965) Respiratory stimulants, 5, 109 (1995) Rhoeadine alkaloids, 28, (1986) S Salamandra group, steroids, 9, 427 (1967) Saraine alkaloids, 73, 223 (2014) Sarpagine-type alkaloids, 52, 104 (1999) Sceletium alkaloids, 19, (1981) Secoisoquinoline alkaloids, 33, 231 (1988) Securinega alkaloids, 14, 425 (1973), 74, (2015) Senecio alkaloids, see Pyrrolizidine alkaloids Sesquiterpene pyridine alkaloids, 60, 287 (2003) Simple indole alkaloids, 10, 491 (1967) Simple indolizidine alkaloids, 28, 183 (1986), 44, 189 (1993), 55, 91 (2001), 75, (2016) Simple indolizidine and quinolizidine alkaloids, 28, 183 (1986), 55, 91 (2001), 75, (2016) Sinomenine, 2, 219 (1952) Solanum alkaloids chemistry, 3, 247 (1953), 74, 216 (2015) steroids, 7, 343 (1960), 10, (1967), 19, 81 (1981) Sources of alkaloids, 1, (1950) Spectral methods, alkaloid structures, 24, 287 (1985) Spermidine and related polyamine alkaloids, 22, 85 (1983), 58, 83 (2002) 508 Cumulative Index of Titles Spermine and related polyamine alkaloids, 22, 85 (1983), 58, 83 (2002) Spider toxin alkaloids, 45, (1994), 46, 63 (1995) Spirobenzylisoquinoline alkaloids, 13, 165 (1971), 38, 157 (1990) Sponges, isoquinolinequinone alkaloids from, 21, 55 (1983) Sri Lankan flora, alkaloids, 52, (1999) Stemona alkaloids, 9, 545 (1967), 62, 77 (2005) Steroid alkaloids Apocynaceae, 9, 305 (1967), 32, 79 (1988) Buxus group, 9, 305 (1967), 14, (1973), 32, 79 (1988), 66, 191 (2008) chemistry and biology, 50, 61 (1998), 52, 233 (1999) Holarrhena group, 7, 319 (1960) Salamandra group, 9, 427 (1967) Solanum group, 7, 343 (1960), 10, (1967), 19, 81 (1981), 74, 204 (2015) Veratrum group, 7, 363 (1960), 10, 193 (1967), 14, (1973), 41, 177 (1992), 74, 204 (2015) Stimulants respiratory, 5, 109 (1955) uterine, 5, 163 (1955) Structure elucidation, by X-ray diffraction, 22, 51 (1983) Strychnine, synthesis of, 64, 104 (2007) Strychnos alkaloids, 1, 375 (part 1) (1950), 2, 513 (part 2) (1952), 6, 179 (1960), 8, 515, 592 (1965), 11, 189 (1968), 34, 211 (1988), 36, (1989), 48, 75 (1996) Sulfur-containing alkaloids, 26, 53 (1985), 42, 249 (1992) Synthesis of alkaloids enamide cyclizations for, 22, 189 (1983) lead tetraacetate oxidation in, 36, 70 (1989) T Tabernaemontana alkaloids, 27, (1983) Taxoids, 69, 491–514 (2010) Taxol, 50, 509 (1998) Taxus alkaloids, 10, 597 (1967), 39, 195 (1990) Terpenoid indole alkaloids, 49, 222 (1997) Thailand, alkaloids from the plants of, 41, (1992) Toxicity to livestock, 67, 143 (2009) Toxicology Papaveraceae alkaloids, 15, 207 (1975) Transformation of alkaloids, enzymatic, microbial and in vitro, 18, 323 (1981) Tremogenic and non-tremogenic alkaloids, 60, 51 (2003) Tropane alkaloids biosynthesis of, 44, 115 (1993) chemistry, 1, 271 (1950), 6, 145 (1960), 9, 269 (1967), 13, 351 (1971), 16, 83 (1977), 33, (1988), 44, (1993) Tropoloisoquinoline alkaloids, 23, 301 (1984) Tropolonic Colchicum alkaloids, 23, (1984), 41, 125 (1992) Tylophora alkaloids, 9, 517 (1967) Cumulative Index of Titles U Uleine and related alkaloids, 57, 235 (2001) Unnatural alkaloid enantiomers, biological activity of, 50, 109 (1998) Uterine stimulants, 5, 163 (1955) V Veratrum alkaloids cevane group of, 41, 177 (1992) chemistry, 3, 247 (1952), 74, 216 (2015) steroids, 7, 363 (1960), 10, 193 (1967), 14, (1973) Veratrum and Solanum alkaloids, 74, 201 (2015) Vinca alkaloids, 8, 272 (1965), 11, 99 (1968), 20, 297 (1981) Voacanga alkaloids, 8, 203 (1965), 11, 79 (1968) W Wasp toxin alkaloids, 45, (1994), 46, 63 (1995) X X-ray diffraction of alkaloids, 22, 51 (1983) Y Yohimbe alkaloids, 8, 694 (1965), 11, 145 (1968), 27, 131 (1986) 509 INDEX Note: Page numbers followed by “f ” indicate figures and “t” indicate tables A (–)-A58365A inhibitor, 16, 17f–18f ACCN See 1,10 -azobis(cyclohexane1-carbonitrile) ACE inhibitor See Angiotensin converting enzyme inhibitor Acetonide, 40–41 Acetylcholinesterase (AChE), 158, 215–216 Acylsilane, radical cyclization of, 401–403 (Z)-alkene, 205, 206f Alkenyl substituents anibamine, 162–165 dendroprimine, 148–152 elaeocarpus alkaloids, 165–177 epimyrtine, 207–215 lupin alkaloids, 179–207 lycopodium alkaloids, 215–221 myrtine, 207–215 plumerinine, 229 porantheridine, 221–229 prosopis alkaloids, 153–159 5,6,7,8-tetrahydroindolizine alkaloids, 159–162 5-alkylindolizidines, 325–326, 327t–328t See also 1,4-disubstituted quinolizidine alkaloids; Epiquinamide; 5,6,8-trisubstituted indolizidine alkaloids Allopumiliotoxins, 424–442 syntheses, 430–434 a-Mannosidases, 117–118 Amat’s enantioselective synthesis, 410f 2-amino-4,6-dimethylpyridine, 163, 164f Aminosugars, 19–20 Amphibians, 286 defensive function of amphibian skin alkaloids, 450 indolizidine and quinolizidine alkaloids, 314–451 Angiotensin converting enzyme inhibitor (ACE inhibitor), 16 Anibamine, 162–165, 162f, 164f Ants, 286, 288–289, 315–317, 324 Anuran alkaloids, 448f APCI See Atmospheric pressure chemical ionization Aromatic gorge, 158 Atmospheric pressure chemical ionization (APCI), 72 Aubé’s synthesis, 380f Aza-Diels–Alder approach, 54–55, 262–263 1-azabicyclo[4.3.0]nonane, 3, 4f 1-azabicyclo[4.4.0]decane, 3, 4f Azasugars, 19–20 1,10 -azobis(cyclohexane-1-carbonitrile) (ACCN), 114–115, 401–403 B Baby hamster kidney-21 cells (BHK-21 cells), 143–144 Barton–McCombie method, 54–55 BChE See Butyrylcholinesterase Beak’s formal synthesis, 30f Benzyloxymethyl (BOM), 13–15 BHK-21 cells See Baby hamster kidney-21 cells Bilberry (Vaccinium myrtillus), 207 bis-(Z)-alkene, 163, 164f Bis(quinolizidine) alkaloids, 465–468, 466f See also Callyimine A; Clathryimines; Piclavines; Stellettamides Blaauw’s original synthesis, 387f Blechert indolizidine, 96, 100–101 BOM See Benzyloxymethyl (E)-boronic acid, 163, 164f (Z)-boronic ester, 163, 164f Borono-Mannich reaction, 20–21 Bovine viral diarrhea virus (BVDV), 143–144 2-bromopyridine, 163, 164f 511 j 512 Bu-CAST See Prodrug 6-Obutanoylcastanospermine (3S,5R,8S,8aS)-3-butyl-5-propyl8-hydroxyindolizine, 312–314 See also Monomorine I; Solenopsis alkaloids Butyrylcholinesterase (BChE), 158 BVDV See Bovine viral diarrhea virus C Callyimine A, 451–452 See also Bis(quinolizidine) alkaloids; Clathryimines; Piclavines; Stellettamides cara torta, 158–159 Castanospermine, 122, 122f–123f See also Lentiginosine biological activity, 140–146 antiviral activity, 143–145 glycosidase inhibition, 141–143 other biological effects, 145–146 isolation and structure, 122–123 synthesis, 123–139 routes employing late-stage bond formation to C-8a, 137–139 routes employing late-stage C-3/N bond formation, 124–129 routes employing late-stage C-6/C-7 bond formation, 135–137 routes employing late-stage N/C-5 bond formation, 129–135 Castanospermum australe (C australe), 122 Celgosivir See Prodrug 6-Obutanoylcastanospermine (+)-Cermizine C, 221 Cha’s “second-generation” synthesis, 462f Chandrasekhar’s approach, 435f Charette’s formal synthesis, 336f Chiral allenyltitanium species, 364–365 Chiral amine (–), 150, 151f (2R,5R)-cis-disubstituted pyrrolidine, 298 Clathryimines, 451–452, 452f Clavepictines, 460–465 Complex quinolizidine-containing marine alkaloids, 451f Constancy hypothesis, 318–319 Corey–Fuchs reaction, 52–53 Index Cotton effects, 168–169 Cyclizidine, 12–15, 12f, 14f–15f D D-Swainsonine See Swainsonine DART-MS See Direct analysis in real time mass spectrometry Dehydrohomopumiliotoxin, 322 Dendroprimine, 148–152, 149f Density functional tight-binding technique (DFTB technique), 72–73 Deoxyribonucleic acid (DNA), 70 DFTB technique See Density functional tight-binding technique (DHQ)2PHAL, 36–37 3,4-di-O-benzyloxy-5,6-Oisopropylidene-d-mannitol, 56 2,3,5,6-Di-O-isopropylidene-Dmannono-1,4-lactone, 49–50 (5E, 9E)-(+)-diastereomer See Indolizidine 195B (5R,7R,8aS)-(–)-diastereomer, 148–150, 149f 3, 5-dibromopyridine, 163, 164f Dietary hypothesis, 286–288, 315–319 (R, R)-dimethyl tartrate, 63–64 (5R,7S,8aR)-(–)-5,7dimethylindolizidine, 148–150, 149f Diol, 175–176, 176f Direct analysis in real time mass spectrometry (DART-MS), 154–155 3,5-disubstituted indolizidine alkaloids, 326–344 routes employing late-stage C-3/N bond formation, 329–337 late-stage C-5/C-6 bond formation, 342–343 late-stage N/C-5 bond formation, 337–342 tandem cyclization with C-3/N/C-8a bond formation, 343–344 5,8-disubstituted indolizidine alkaloids, 344–345, 350f, 449–450 513 Index route employing tandem N/C-5/C-8a bond formation, 372–374 routes employing late-stage bond formation to C-7, 368–372 routes employing late-stage C-3/N bond formation Liebeskind’s syntheses, 352–357, 353f other approaches, 357–363 Toyooka and Nemoto contributions, 345–351 routes employing late-stage N/C-5 bond formation, 363–368 1,4-disubstituted quinolizidine alkaloids, 406–420 See also 5-alkylindolizidines; Epiquinamide; 5,6,8-trisubstituted indolizidine alkaloids 1-ethyl-4-substituted quinolizidine alkaloids, 415–420 quinolizidine 207I, 406–411 quinolizidine 217A, 411–415 4,6-disubstituted quinolizidine alkaloids, 420–424 DNA See Deoxyribonucleic acid Double hydroformylation strategy, 399–400 “epi-Gallagher” intermediate, 438 (–)-2-epi-Lentiginosine, 27f, 28 Epibatidine, 384, 385f Epilupinine, 182f, 184 syntheses of, 193–205 Epimyrtine, 207–215 (4R,9aS)-(–)-epimyrtine, 207, 207f Epiquinamide See also 5-alkylindolizidines; 1,4-disubstituted quinolizidine alkaloids isolation, characterization, and biological activity, 384–385 syntheses, 386–406 Epoxyamine, 32 Erwinia amylovora (E amylovora), 16–18 (1-ethoxy)ethyl (EE), 261–262 1-ethyl-4-substituted quinolizidine alkaloids, 415–420 (7S)-(+)-2-ethyl-7-hydroxy-6, 7-dihydro-3(5H)-indolizinone, 15, 16f Eugenia uniflora (Myrtaceae), 146–147 Experimental autoimmune encephalomyelitis (EAE), 145–146 E Fabaceae See Leguminosae family Ficuseptine, 247, 248f EAE See Experimental autoimmune encephalomyelitis ECD See Electronic circular dichroism Ecuadoran frog E tricolor, 384 EE See (1-ethoxy)ethyl Elaeocarpus alkaloids biogenesis, 169 isolation and characterization, 165–169 synthesis, 169–177 Electronic circular dichroism (ECD), 15 Enantiomer of 49 (ent-49), 13–15 ent-49 See Enantiomer of 49 (+)-entiginosine, 30–31, 31f (1R,6S,7R,8R,8aR)-(–)-1-epicastanospermine, 123–124 (+)-5-epi-dendroprimine (ent), 150, 151f (+)-7-epi-dendroprimine, 149f (Ỉ)-8a-epi-dendroprimine, 152f 8a-epi-dendroprimine, 149f, 151–152 F G Garner aldehyde, 91–92, 396–398 (R)-glyceraldehyde, 38–39 Glycosidase inhibition, 116–118, 141–143 Grandisine D, 165–166, 166f, 175–176, 175f Graviola, 69 H Harrity’s synthesis, 296f, 414–415 HBV See Hepatitis B virus HCV See Hepatitis C virus Heat shock protein 90 (Hsp90), 28 Helmchen’s synthesis, 340f Hepatitis B virus (HBV), 144 Hepatitis C virus (HCV), 143–144 HIV See Human immunodeficiency virus 514 Homopumiliotoxin, 321, 321f, 442–447 Honey mesquite See Prosopis glandulosa Torrey var glandulosa Horner–Wadsworth–Emmons coupling, 330–331 Hsp90 See Heat shock protein 90 Human immunodeficiency virus (HIV), 145 HIV-1, 143 (+)-Hupeol synthesis, 205–207 Hyacinthaceae, 64–65 (–)-hyacinthacine A5, 64–65, 65f 1-Hydroxyindolizidines, 21–26, 21f Hydroxylated indolizidine alkaloids castanospermine and related compounds, 122–146 general reviews, 19–21 lentiginosine and related compounds, 26–64 putative uniflorines, 146–148 steviamine, 64–68 swainsonine, 69–121 Hydroxyquinolizidinone, 443–445 I IL-2 See Interleukin-2 Imine (+), 258–259, 258f Iminosugars See Aminosugars Indolizidine 195B, 329 Indolizidine alkaloids See also Hydroxylated indolizidine alkaloids from amphibians, 314–315 5-alkylindolizidines, 325–326, 327t–328t allopumiliotoxins, 424, 430–434 biological activity, 447–451 from bufonid toads, 323f from dendrobatid and mantellid frogs, 322f dietary hypothesis, 315–319 3,5-disubstituted indolizidine alkaloids, 326–344 5,8-disubstituted indolizidine alkaloids, 344–374 1,4-disubstituted quinolizidine alkaloids, 406–420 Index 4,6-disubstituted quinolizidine alkaloids, 420–424 epiquinamide, 384–406 homopumiliotoxins, 442–447 isolation and characterization, 319–325 pumiliotoxins, 424–429, 434–442 5,6,8-trisubstituted indolizidine alkaloids, 374–383 from arthropods, 286 bicyclic alkaloids of Myrmicaria melanogaster, 290f (3S, 5R, 8S, 8aS)-3-butyl-5-propyl8-hydroxyindolizine, 312–314 isolation and characterization, 286–291 monomorine I, 292–309 non-stereospecific synthesis, 292f pumiliotoxins isolation, 289f representative alkaloids from mites, 288f solenopsis alkaloids, 309–312 from fungal and microbial sources cyclizidine, 12–15, 12f, 14f–15f JBIR-102, 12–15, 12f Pantocins A and A2, 16–18, 19f slaframine, 5–12, 7f–8f, 10f Streptomyces metabolites, 15–16 from marine sources, 451 bis(quinolizidine) alkaloids, 465–468, 466f callyimine A, 451–452 clathryimines, 451–452, 452f clavepictines, 460–465 piclavines, 456–460, 457f pictamine, 460–465 stellettamides, 452–455, 453f INOC See Intramolecular nitrile oxide cycloaddition Interleukin-2 (IL-2), 145–146 Intramolecular nitrile oxide cycloaddition (INOC), 204–205 Ipalbidine, 231–235, 235f isolation and characterization, 229–230 synthesis, 230–235 Ipalbidinium, 230 (–)-isoelaeocarpiline, 165–166 515 Index 2,3-O-isopropylidene-Derythronolactone, 102–103 Izidine alkaloid, 3, 286–288 J JBIR-102, 12–15, 12f Julandine, 236f isolation, characterization, and biological properties, 237–238 and related alkaloids, 235–236 synthesis, 238–247 Juliflorine See Juliprosopine Juliprosine, 153, 154f, 156–158 synthesis of, 157f Juliprosopine, 153, 154f, 155–158, 153, 16 synthesis of, 157f (R)-b-keto sulfoxide (+), 51–52 K Kibayashi’s syntheses, 426f, 454f L LACDAC See Lewis acid-catalyzed dieneealdehyde cyclocondensation (2S,4S,9aR)-(–)-lasubine, 248, 249f (2S, 4S, 9aS)-(–)-lasubine, 248, 249f Late-stage C-4/N bond formation, 254–256 Leguminosae family, 69 Lentiginosine, 26–28 See also Castanospermine isolation and biological activity, 28 synthesis, 28–64 Aza-Diels–Alder approach, 54–55 routes employing double cyclization with C-3/N/C-5 bond formation, 51–53 routes employing late-stage acylative C-3/N bond formation, 36–39 routes employing late-stage alkylative C-3/N bond formation, 30–36 routes employing late-stage C-1/C-2 bond formation, 29–30 routes employing late-stage C-6/C-7 or C-7/C-8 bond formation, 55–62 routes employing late-stage C-8/C-8a bond formation, 62–64 routes employing late-stage N/C-5 bond formation, 40–51 Lesma’s synthesis, 300f Lewis acid-catalyzed dieneealdehyde cyclocondensation (LACDAC), 176–177 LiDBB See Lithium di-tert-butyldiphenyl Liebeskind’s “second-generation” approach, 353–357 Liebeskind’s synthesis, 352–357, 353f, 420 Lithium di-tert-butyldiphenyl (LiDBB), 13–15, 207–208 Locoweeds, 69 Lupin alkaloids occurrence and characterization, 179–181 and sources, 180t–181t structural investigations, 181–184 synthesis, 184–207 Lupinine, 182f, 183–184 syntheses of, 193–205 Lycopodium alkaloids isolation and characterization, 215–216 synthesis, 216–221 Lysosomal storage diseases, 118–119 Lythraceae alkaloids, 248–274 isolation and characterization, 248–250 synthesis, 250–274 M Ma’s formal synthesis, 361f Ma’s synthesis, 463f MDL 28,574 See Prodrug 6-Obutanoylcastanospermine Mearsamine, 167, 168f Metathesis catalysts, 6f Methyl a-D-glucopyranoside, 138–139 Mites, 286–288 oribatid, 286–287, 315–317 representative alkaloids from, 288f Monomorine I, 292 See also (3S,5R,8S,8aS)-3-butyl-5-propyl8-hydroxyindolizine; Solenopsis alkaloids asymmetric catalytic hydrogenation of indolizines, 308–309 enantioselective syntheses, 293 rac-1562, 292–293, 293f 516 Monomorine I (Continued ) routes employing late-stage C-3/N bond formation, 294–298 late-stage N/C-5 bond formation, 298–305 tandem cyclizations with C-3/N/C-8a or C-5/N/C-8a bond formation, 306–308 Myrtaceae See Eugenia uniflora Myrtine, 207–215 (4R,9aR)-(+)-myrtine, 207, 207f N N-(but-3-enoyl) metathesis precursor (–), 191–192, 191f N-benzyl-2-(p-toluenesulfonyl)acetamide, 151–152, 152f N-methylpyrrolidone (NMP), 5–7 nAChRs See nicotinic acetylcholine receptors Natural Product Reports, nicotinic acetylcholine receptors (nAChRs), 447, 449 Nitrone, 130–132 NMP See N-methylpyrrolidone Nubbemeyer’s approach, 439 Nuphar alkaloids, 275 isolation and biological activity, 275–276 nuphar indolizidine syntheses, 280–283 nuphar quinolizidines syntheses, 276–280 O Octahydro-2H-quinolizine, 3, 4f Octahydroindolizine, 3, 4f Odontotermes formosanus (O formosanus), 15 Organo-SOMO catalysis, 109–110 Overman’s “second-generation” synthesis, 429 3-oxojuliprosine, 153–154, 154f 30 -oxojuliprosine, 153–154, 154f P p-nitrobenzyl (PNB), 251–252 Pantocins A and A2, 16–18, 19f Pantoea agglomerans (P agglomerans), 16–18 Index Parikh–Doehring oxidation, 234–235, 330–331 PCR See Polymerase chain reaction Petasis reaction See Borono-Mannich reaction Petrosin, 465–468, 466f Piclavines, 456–460, 457f See also Bis(quinolizidine) alkaloids; Callyimine A; Clathryimines; Stellettamides Pictamine, 460–465 “Pie face” See cara torta Pivotal amine syntheses, 456f Plant indolizidine and quinolizidine alkaloids See also Indolizidine alkaloids ficuseptine, 247 ipalbidine and related alkaloids, 229–235 julandine and related alkaloids, 235–247 lythraceae alkaloids, 248–274 nuphar alkaloids, 275–283 quinolizidine–quinazoline alkaloids, 283–285 septicine and related alkaloids, 235–247 Plumerinine, 229 PNB See p-nitrobenzyl “Poison frogs” alkaloids, 287–288, 319 Polygonatum alkaloids, 159f Polymerase chain reaction (PCR), 70–71 Poranthera corymbosa (P corymbosa), 221–222 Porantheridine, 221–229 Prodrug 6-O-butanoylcastanospermine, 140–141, 141f (9Z)-3-propylindolizidine, 290–291 Prosopilosidine, 155–156, 155f (+)-Prosopilosine, 155–156, 155f Prosopis alkaloids, 153–159 Prosopis glandulosa Torrey var glandulosa, 155–156 Pumiliotoxins, 321, 321f, 424 formal syntheses and model studies, 434–442 isolation, 289f syntheses, 424–429 Putative uniflorines, 146–148 Pyrrolidin-2-one, 45–46 517 Index Q swainsonine toxicosis and lysosomal storage diseases, 118–119 occurrence, isolation, and characterization, 69–73 synthesis, 73–116 routes employing late-stage bond formation to C-8a, 112–116 routes employing late-stage C-1/C-2 bond formation, 74–82 routes employing late-stage C-3/N bond formation, 83–93 routes employing late-stage C-6/C-7 bond formation, 110–112 routes employing late-stage N/C-5 bond formation, 93–106 routes employing tandem cyclizations with C-3/N/C-5 or N/C-5/C-8a bond formation, 106–110 Quinolizidine 207I, 406–411 Quinolizidine 217A, 411–415 Quinolizidine alkaloids See 1,4-disubstituted quinolizidine alkaloids Quinolizidine–quinazoline alkaloids, 283–285 R Racemic N-Cbz-piperidine-2carbaldehyde, 403–404 Ruthenium-containing catalysts, S (+)-Sarusubine A, 249–250, 249f Sato’s synthesis, 365f Secoantofine synthesis, 241–242 Secophenanthroindolizidine alkaloids, 237–238 Septicine, 236f isolation, characterization, and biological properties, 237–238 and related alkaloids, 235–236 synthesis, 238–247 Skeletal rearrangement, ring closure involving, 272–274 Slaframine, 5–12, 7f–8f, 10f Solenopsis alkaloids, 309–312 See also Monomorine I Soursop See Graviola Sparteine surrogate, 78 Stellettamides, 452–455, 453f See also Bis(quinolizidine) alkaloids; Callyimine A; Clathryimines; Piclavines Stevenson’s synthesis, 459f Steviamine, 64–68, 65f, 68f Streptomyces koyangensis (S koyangensis), 15 Streptomyces metabolites, 15–16 Swainsonine, 69, 73f biological activity anticancer and immunomodulatory effects, 120–121 glycosidase inhibition, 116–118 T Takemoto’s synthesis, 409f (R,R)-(+)-tartaric acid, 55–56 Tashiromine, 182f, 184–193 TCC chloroformate See (+)-trans-2(a-cumyl)-cyclohexyl chloroformate 5,6,7,8-tetrahydroindolizine alkaloids, 159–162 Thallium(I) acetate, 440–442 Thermotoga maritima (T maritima), 117 Tokuyama’s synthesis, 467f Toyooka and Nemoto contributions, 345–351 (+)-trans-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloroformate), 430–431, 431f 1,7,8-tri-O-acetyl-6-Obenzoylcastanospermine, 122–123 5,6,8-trisubstituted indolizidine alkaloids, 374–383 (S)-(+)-Tylophovatines, 237f, 238 W Weinreb amides, anionic cyclization of, 47–49 ... alkaloid chemistry The present book is the 75th volume and thus represents a jubilee for The Alkaloids In the long history of this series, single-topic volumes have been very rare: Volume 25, published... subset of the compounds in the cited reviews, they are the focus of yet another review that concentrates on total synthesis.66 The application of specific reactions to the synthesis of iminosugars... of the target’s C-8a stereochemistry and the position of the nitrogen atom (Scheme 5).33 In tackling the challenge of creating the six contiguous stereogenic centers, they next installed the