Indole Alkaloids: An Introduction to the Enamine Chemistry of Natural Products

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PREFACE

THIS book owes its genesis to a request, made by Sir Robert Robinson on the occasion of his seventy-seventh birthday, to write a monograph on indole alkaloids. I have stated concisely my views on the chemistry and interrelationships between indole alkaloids which should be of value to teachers, a challenge to students and even interesting to practitioners of the art.

I owe much to the management of CIBA Pharmaceutical Company for creating the environment which made possible certain contributions to the chemistry discussed on the subsequent pages.

I am indebted to Dr. E. Schlittler who read the entire manuscript and made many helpful suggestions. My thanks are also due to Miss Susanne Hay who typed the manuscript and to Charles Gemenden for his help in the proofreading.

W.I.T.,     Summit, N.J.

October, 1964

INTRODUCTION

AT THE dawn of experimental organic chemistry just over a century and a half ago, Sertürner isolated morphine from opium. Although he was not the first man to do so he did recognize it to have basic properties and referred to it as a vegetable alkali. Meisner in 1818 proposed that such vegetable alkalis should be called alkaloids. This noun became accepted and today the word generally denotes a basic, physiologically active nitrogen heterocycle of some complexity obtained from plant sources. This definition however does not prevent the chemist from considering in the same context and for reasons of chemical or physiological properties simple primary amines such as the cactus hallucinogen, mescaline, the neutral mitotic poison, colchicine from the autumn crocus; the nitrophenanthridine, aristolochic acid from Aristolochia sipho; and even complex pharmacologically active bases of animal origin, inter alia, dehydrobufotenine from the toad and samandarine from the salamander.

In this book we shall concern ourselves with the chemistry of selected alkaloids which contain indolic or closely related nuclei and greater emphasis will be placed on developing the chemistry of the complex indoles than rigid proofs of their structures or syntheses. Some five hundred of these bases have been obtained from about three hundred plants mostly of the family Apocynaceae. The alkaloids fall into two broad classes in which a tryptophan residue or its equivalent is either (a) in combination with a ten carbon moiety and this forms the greater majority of the bases or (b) modified slightly by alkylation, ring closure or fusion to an anthranilic or mevalonic acid