THE ALKALOIDS Chemistry and Pharmacology Volume 29 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 29 1986 ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers Orlando San Diego New York Austin Boston London Sydney Tokyo Toronto COPYRIGHT 0 1986 BY ACADEMIPCR ESS, 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 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 CONGRESS CATALOG CARD NUMBER 50-5522 ISBN 0- 12-469529-9 PRINTED IN THE UNITED STATES OF AMERICA 86 87 88 89 9 8 7 6 5 4 3 2 1 CONTENTS PREFACE.. .................................................................... vii Chapter 1. Chemotaxonomy of Papaveraceae and Fumariaceae V. PREININGER 1. Introduction ....................................................... 1 11. Chemotaxonornic Evaluatibn of the Papaveraceae ......................... 3 111. Chemotaxonomic Evaluation of the Fumariaceae ......................... 51 IV. Alphabetic Listing of the Papaveraceae and Fumariaceae Alkaloids and Their Formulas .......................................................... 66 References ........................................................ 92 Chapter 2. Quinazoline Alkaloids SIEGFRIEJDO HNE I. Introduction ....................................................... 99 11. Simple Substituted Quinazolin-4-ones .................................. 99 111. The Pyrroloquinazolines ... .... 111 IV. The Pyrido[2,1 -b]quinazolines ........................................ 121 V. The Indoloquinazolines .............................................. I23 VI. Biosynthesis ....................................................... I25 VII. Biological Activity of Quinazoline Alkaloids and Their Analogs ............. I29 References ................ .... 135 Chapter 3. The Naphthyl Isoquinoline Alkaloids GERHARDB RINGMANN ... ... ........ ......... 141 11. Alkaloids from Ancistrocladaceae ...................................... 142 111. Alkaloids from Dionchophyllaceae ..................................... 145 IV. Biosynthesis of Naphthyl Isoquinoline Alkaloids ............. 154 V. The Biomimetic Synthesis of Acetogenin Isoquinoline Alkaloids ............ 163 VI. Concluding Remarks ................................................ 181 References .................. ........................... 182 V vi CONTENTS Chapter 4. Alkaloidal Substances from Aspergillus Species YUZURUY AMAMOTAON D KUN~ZAOR A~ I. Introduction ....................................................... I85 11. Pyrazine Metabolites ................................................ 185 111. Diketopiperazine Metabolites Derived from Tryptophan and Alanine ......... 192 IV. Diketopiperazines Derived from Tryptophan and Proline ................... 20 1 V. Other Diketopiperazines Derived from Tryptophan ........................ 209 VI. Diketopiperazines Derived from Phenylalanine ........................... 21 1 VII. Metabolites Derived from Tryptophan and Anthranilic Acid ................ 218 VIII. Indole-Mevalonate Metabolites ....................................... 225 IX. Bisindolylbenzoquinone Metabolites .................................... 229 X. Miscellaneous Metabolites ............................................ 236 References ........................................................ 254 Chapter 5. The Daphniphyllum Alkaloids SHOSUKYE AMAMURA I. Introduction ....................................................... 265 11. Structures and Properties ............................................. 266 111. Pharmacological Properties ........................................... 284 References ........................................................ 286 Chapter 6. The Cularine Alkaloids Luis CASTEDOA ND RAFAELS UAU 1. Introduction ..... ...... 287 11. Occurrence and Cla ......................................... 288 111. Physical and Chemical Properties ...................................... 288 IV. Total Synthesis ..................................................... 308 V. Stereochemistry .................................................... 316 VI. Biosynthesis ....................................................... 3 17 VII. Pharmacological Properties ........................................... 322 References ........................................................ 322 INDEX ........................................................................ 325 PREFACE It is sad to report that Dr. V. Preininger, who wrote the chapter on “Chemo- taxonomy of Papaveraceae and Fumariaceae Plants,” and for many years a member of the famous SantavL team at the Medical Faculty of the Palacky University in Olomouc, Czechoslovakia, passed away shortly after the writing of his article. His review, the first of its kind in this treatise, will for this reason remain a memorable event. “Quinazoline Alkaloids,” discussed in Vols. 3 and 7 of this treatise, have now been updated, and more than 60 members are being presented under the new heading “Simple Substituted Quinazoline Alkaloids,” including pharmacological details for several representatives. “Naphthyl Iso- quinoline Alkaloids,” not made in nature by conventional isoquinoline biosyn- thetic pathways including Mannich condensation, but of polyketide origin, are presented here for the first time. This group of alkaloids was first recognized to exist by Professor T. R. Govindachari, and the review is honoring his contribu- tion. “Alkaloidal Substances from Aspergillus Species,” derived from amino acids rather than amines, is an excursion into the field of fungal metabolites, often produced besides antibiotics during fermentation. ‘‘Daphniphyllum Al- kaloids,” now comprising 14 members, were first discussed in Vol. 15 of this treatise. It is amazing that during the 10 years which have elapsed none of these alkaloids has been synthesized, making this group a challenge to chemists. The cularine alkaloids, reviewed earlier in Vols. 4 and 10 of this treatise, now comprise more than 30 individual alkaloids, which are presented here with details on their structures and synthesis. Arnold Brossi vii This Page Intentionally Left Blank CHAPTER 1 __ CHEMOTAXONOMY OF PAPAVERACEAE AND FUMARIACEAE V. PREININCER* Institute of Chemistry, Medical Faculty, Palackj University, Olomouc, Czechoslovakia I. Introduction The families Papaveraceae and Fumariaceae are well known as taxonomic groups, and both are very rich in specific alkaloids. Some of them are important in medicine and some others can be considered as promising in this sense (I ,2). Therefore it is not surprising that in the past and especially at present these alkaloids belong to those that have been most intensively studied (3-9). A vast quantity of material has been accumulated, which represents a rich potential source of medicinal compounds of plant origin and a significant taxon in plant systematics. In this connection, attempts are made by both botanists and chem- ists to find a correlation between chemical properties and botanical features. Alkaloids with one chiral carbon are shown as racemic mixtures, but their enantiomeric characterization is given in the text with the prefix (-) or (+). In the formulas of alkaloids with more than one chiral center the relative and absolute configurations are omitted. However, these structural details can be found in the literature [Refs. 3-8, 16, and previous volumes of this treatise: Simple Isoquinolines, Vol. 21 (1983), p. 255; Aporphines, Vol. 24 (1985), p. 153; Phthalideisoquinolines, Vol. 24 (1985), p. 253; Benzophenanthridines, Vol. 26 (1985), p. 1851. The taxonomic delineation of the families Papaveraceae and Fumariaceae is not uniform. Fedde (IO), Tutin ef al. (I]), or Melchior (12) classified the fumariaceous plants in the Papaveraceae, as the subfamily Fumarioideae, where- as Hutchinson (13)c onsidered the Fumariaceae to be an independent family. The Occurrence of isoquinoline alkaloids in those plants indicates a close relationship of the Papaveraceae and Fumariaceae to the Polycarpicae and to the orders Ranales and Magnoliales (14). Formerly, the order Rhoeadales included the Papaveraceae and the Fumariaceae, as well as the Brassicaceae, Capparaceae, * Deceased December 22, 1985. 1 THE ALKALOIDS. 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