Researches into the synthesis of some degradation products of emetine

Abstract

The root bark of several species of the ipecacuanha plant, notably Cephaelis ipecacuanha and Psychotria acuminate, contains at least five alkaloids, of which the principal one is emetine. The minor alkaloids are closely related to emetine, and the elucidation of their structures follows directly from the structure of emetine. The chief interest in emetine lies in its peculiar therapeutic powers as a treatment for amoebic dysentery. The drug has other medicinal properties as an emetic and diaphoretic, but these have largely been superseded, and in any case do not compare with its importance as a specific against entamoeba histolytica, the organism responsible for the occurrence of amoebic dysentery. Its local irritant effects, however, render it unsuitable in some cases, and although various simple derivatives have been used in its place, none of them appear to be a significant improvement on emetine itself. The main hope of producing a more suitable therapeutic agent lies in a more radical alteration of the molecule, and before this can be attempted, the structure and properties of emetine must be known beyond all doubt. Natural and synthetic substitutes for emetine produced with this knowledge, have so far proved ineffective. The structure of emetine, however, is now known with virtual certainty, apart from a complete synthesis of the molecule itself, and progress in this field should be more rapid. The investigations recorded herein are part of a continuation of the series (1, 2, 3, 4) which has finally shown the structure of emetine clearly, and with it the structures of the minor alkaloids and the rubremetine salts (2). The present work is mainly concerned with synthetic investigations of the more immediate degradation products from emetine, with the aim of further confirming the molecular structure. A parallel aim has been the provision of suitable intermediates for analogous syntheses.