Enige eenvoudige reserpine-analoga

Abstract

In this thesis two syntheses of 1,2,3,4,6,7,12,12b-octahydro-pyrido [2,1-alo-carbolines, substances containing alarge part of the reserpine structure, are described. In the first method the starting materials were tryptamine (XVII) and 0-hydroxymethyleneglutaric acid diethylester (I) (Chapter 11). Instead of tryptamine also 2-(3,4-dimethoxypheny1)-ethylamine and other primary amines were used as model substances (Chapter I). Catalytic reduction as wel1 as reduction with LiA1H4 of the product XXII resulted in a compound with a trans (3H, 1 2 ~c~on1fig uration. On the contrary, reduction with zinc and diluted perchloric acid yielded mainly the less stable cis-isomer (Chapter 11, reaction scheme page 37 1. From trans (3H, 12%) 3-hydroxymethyl-l, 2, 3, 4, 6, 7, 12, 12b -0ctahydro-pyrido f 2, l-a] p-carboline (XXV) the 3,4,5-trimethoxybenzoic acid ester (XXVIi was prepared and, via the p-toluenesulfonate, the corresponding cyanide (Chapter 11). In the second method 5-ethyl-2-methylpyridine was the starting compound (Chapter 111, reaction scheme page 49). The product obtained was cis (3H, 12b~)3-ethoxycarbonyl-1,2 .3,4, 6,7,12, 12b-octahydro-pyrido [2, l - a ] P-carboline (XXIV). This implies formation of cis-2,5-bis(methoxycarbony1)piperidine (XXXI) bij catalytic reduction of dimethyl pyridine-2,5-dicarboxylate (XXX). The pharmacologicalproperties of trans (3H, 1 2b H) 3-hydroxymechyl-l, 2, 3, 4, 6, 7, 12, l ~ ~ - o c t a h y d r o - ~ ~1r2i, dl -oa l p - carbolino (XXV) and his 3,4,5-trimethoxybenzoic acid ester (XXVI) were found to be qiialitatively similar to those of reserpine, but quantitatively the compounds were less effective (Chapter IV).