Total synthesis of polymethoxyoestrane compounds. Part I. Synthesis of (±)-2,3,4-trimethoxyoestra-1,3,5(10)-trien-17β-ol and related compounds

Abstract

By use of general procedures developed for (±)-oestrone, 2,3,4-trimethoxyoestra-1,3,5(10)-trien-17β-ol (7) has been totally synthesized from 3,4-dihydro-5,6,7-trimethoxynaphthalen-1(2H)-one (1). Metal–ammonia reduction of the intermediate 2,3,4-trimethoxyoestra-1,3,5(10),8-tetraen-17β-ol (6) under the usual conditions caused loss of the 3-methoxy-group. Reduction under carefully controlled conditions was necessary to obtain the trimethoxyoestratrienol (7). A series of stereoisomers of (±)-2,3,4-trimethoxyoestranes has been prepared for evaluating biological activity.