THE ALKALOIDS Chemistry and Pharmacology Volume 28 THE ALKALOIDS Chemistry and Pharmacology A list of contents of volumes in this treatise is available from the publisher on request. THE ALKALOIDS Chemistry and Pharmacology Edited by Arnold Brossi National Institutes of Health Bethesda, Maryland VOLUME 28 1986 W ACADEMIC PRESS, INC. Harcourt Brace Jovunovich, Publishers Orlando San Diego New York Austin Boston London Sydney Tokyo Toronto COPYRIGH0T 1986 BY ACADEMIPCR ESSI NC ALL RIGHTS RESERVED NO PART OFTHIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS. ELECTRONIC OR MECHANICAL. INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER ACADEMIC PRESS. INC Orlando. Florida 32887 United Kingdom Edition published by ACADEMIC PRESS INC. (LONDON) LTD. 24-28 Oval Road. London NW I 7DX LIBRAROYF CONGRESCSA TALOCGA RDN UMBER: 50-5522 ISBN 0-12-469528-0 (alk. paper) PRINTED IN THE UNITED STATES OF AMLRlCA 86 87 88 89 9 8 7 6 5 4 3 2 I CONTENTS PREFACE.. .............................................................. vi i Chapter 1 . Rhoeadine Alkaloids H . RONSCH I . Introduction ....................................................... i I1 . Alkaloids and Plants ................................................ 2 I11 . Structure Elucidation and Related Chemistry ............................. 9 IV . Chemistry Excluding Synthesis ........................................ 33 V . Synthesis .......................................................... 41 VI . Spectroscopy .............. .... ..................... 59 VII . Biosynthesis ....................................................... 66 VIII . Biological Activity .................................................. 78 IX . Physicochemical Data of Rhoeadine Alkaloids and Derivatives .............. 86 References ........................................................ 86 Chapter 2 . Protoberberine Alkaloids D . S . BHAKUNAIN D S . JAIN I . Introduction ....................................................... 95 11 . Occurrence ........................................................ 95 I11 . Revised Structures .................................................. 103 IV . New Alkaloids .............. ................................... 104 V . Chemical Reactions . ............................................ 114 VI . Synthesis of Berbines ............................................ 134 VII . Spectroscopic Properti ............................................ 152 VIII . Absolute Configuration ................................... 155 IX . Biosynthesis ....................................................... 157 X . Pharmacological Properties ........................................... 169 References ........................................................ 171 Chapter 3 . Simple Indolizidine and Quinolizidine Alkaloids ARTHURS . HOWARDAN D JOSEPHP . MICHAEL I . Introduction ....................................................... 183 I1 . 6-Coniceine ........................................................ 185 V vi CONTENTS I11 . Alkyl. Functionalized Alkyl. and Acylindolizidine Alkaloids ................ i92 IV . AIkyl and Functionalized Alkyl Quinolizidine Alkaloids ................... 218 V . Arylindolizidine and Arylquinolizidine Alkaloids ......................... 225 VI . Sesquiterpenoid Indolizidine and Quinolizidine Alkaloids .................. 246 VII . Alkaloids of the Papilionideae: Simple Lupine Quinolizidines ............... 256 VIII . Slaframine ......................................................... 263 IX . Polyhydroxylated Indolizidines ........................................ 215 X . Addendum ........................................................ 291 References ........................................................ 298 INDEX ................................................................. 309 PREFACE The editor-in-chief of this treatise notes with great pleasure that scientists from 18 different countries have contributed to the writing of articles in the last eight volumes, attesting to the fact that the study of alkaloids is a multidisciplinary and international affair. The diverse group of isoquinoline alkaloids, discussed by Santavjj in Vol. 17 of this text under the heading “Papaveraceae Alkaloids,” has been broken up further. “Rhoeadine Alkaloids,” discussed in this volume, represent the newest subgroup, including until now about 40 individual representatives of largely unknown pharmacological potential. ‘‘The Protoberberine Alkaloids,” on the other hand, discussed twice before, have been brought up to date. The chapter also includes a discussion of pharmacological properties of representative al- kaloids. The third chapter, “Simple Indolizidine and Quinolizidine Alkaloids,” avoids discussion of representatives with fused polycyclic ring systems, such as ‘‘Phenanthroindolizidinea nd Phenanthroquinolizidine Alkaloids, and alkaloid ” families, such as “Lupine Alkaloids,” “Elaeocarpus Alkaloids,” “Lythraceae Alkaloids,” and “Nuphar Alkaloids,” which will be discussed separately. The alkaloids discussed here are representatives of a cross-section of natural sources, including fungi, higher plants, insects, amphibians, and mammals, and the chap- ters concentrate on chemical synthesis, stereochemical aspects, and some in- triguing biological properties of these interesting molecules. Arnold Brossi vii This Page Intentionally Left Blank -CHAPTER 1 - RHOEADINE ALKALOIDS H. RONSCH Institute of Plant Biochemistry The Academy of Sciences of the German Democratic Republic Halle (Saale), German Democratic Republic I. Introduction The rhoeadine alkaloids are always classified with the big isoquinoline family of alkaloids to which they are closely related biogenetically, although in struc- tural terms they differ in having a 3-benzazepine entity. Since 1965, when the correct structure for rhoeadine emerged in the literature, the rhoeadine alkaloids’ plant sources, chemistry, biosynthesis, and other concerns have been incorporat- ed into review papers on Papaveraceae or isoquinoline alkaloids, such as those by Manske (99) or Santavy (177, 178) in this series. Others from Pfeifer’s group (93, 129, 140) put more emphasis on history and early chemistry as well as on botanical and phytochemical aspects. Shamma in his books on the isoquinoline alkaloids (194, 196) dealt with substantial chemistry, synthesis, and biosynthesis of the rhoeadine alkaloids and, together with Montgomery efa l. (103,p rovided a useful compilation of their structural, physical, and spectral data, A similar liSting that was combined with an outline of their basic chemistry had already been made available by Kametani (73). Dopke’s (33,C ordell’s (29,o r Robin- son’s (160) books dealing with the field of alkaloids include concise reports on chemistry and/or biosynthesis. The Specialist Periodical Report series on al- kaloids (11, 50, 103) has given brief reference as to occurrence, chemistry, and biosynthesis of rhoeadine alkaloids for each year since 197 1. Chemotaxonomic aspects of Papaveraceae alkaloids, among them the rhoeadines, have been dis- cussed by Preininger (151a). Being the first treatise on the rhoeadine alkaloids of their own, at least in this series, this review should gather all pertinent information from the literature or previous reports to be as comprehensive as feasible. This, however, does not mean that early chemistry and historical or phytochemical aspects are to be considered in every detail; instead, the reader is referred to previous reviews. Parallel work that merely repeats previous original studies has been outlined briefly or even omitted. I THE ALKALOIDS. VOL. 28 Copyright 0 1986 hy Academic Prcs. Inc.