Synthesis of 17α-ethynyl-7α,11β-dihydroxyestra-1,3,5(10)-triene-3,17β-diol

Abstract

17α-Ethynyl-7α,11β-dihydroxyestradiol (9) was synthesized starting from androsta-1,4,6-triene-3,11,17-trione (1). Compound (1) was acetalized selectively at C-17 with ethylene glycol to give the ethylene acetal (4). Selective reduction of the 11-oxo-group in compound (4), followed by aromatization of ring A with zinc and acetylation gave the diacetate (6b) which, on epoxidation followed by reduction with lithium aluminium hydride and subsequent hydrolysis, gave the 7α,11β-dihydroxy-derivative (8) which was ethynylated to give the title compound (9).The diol (9) shows a poorer separation of postcoital antifertility activity from uterotropic activity in the rat than do either the 7α- or 11β-monohydroxyanalogues.