Steroidal αβ-Epoxyketones. II. Synthesis of 6α-Bromo-4α,5-epoxy-5α-cholestan-3-one and Its 4β,5β-Isomer

Abstract

An efficient method for the epimerization of 6β-bromocholest-4-en-3-one (III) to 6α-bromocholest-4-en-3-one (V) via 6-bromo-3-ethoxycholesta-3,5-diene (VI) is described. Owing to the lability and unusual properties of several 6a-brominated intermediates, special experimental procedures were required for the conversion of (V) to 6α-bromo-4α,5-epoxy-5α-cholestan-3-one (XVIII) and its 4β,5β-isomer (XVI). Thus, diborane reduction of 6α-bromocholest-4-en-3-one (V) gave a high yield of the corresponding 3β-alcohol (IV; R = H) which upon epoxidation with trifluoroperacetic acid and chromatography of the product over florid yielded 6α-bromo-4β,5-epoxy-5β-cholestan-3β-ol (XVII; R = H), and its 4α,5α-isomer (XV; R = H). Chromic acid-acetone oxidation of the isomeric epoxyalcohols (XV; R = H) and (XVII; R = H) afforded 6α-bromo-4α,5-epoxy-5α-cholestan-3-one (XVIII) and 6α-bromo-4β,5-epoxy-5β-cholestan-3-one (XVI), respectively.