18-Substituted steroids. Part 11. Synthesis of 3β,16α,18-trihydroxyandrost-5-en-17-one, a neonatal urinary metabolite, and the 3,16,18-triacetate of its 16β-epimer

Abstract

3β,16α,18-Trihydroxyandrost-5-en-17-one and the triacetate of its 16β-epimer have been synthesized from 3β-hydroxypregna-5,16-dien-20-one via the ‘hypoiodite’ reaction of the derived 3β-acetoxy-16α,17α-epoxypregn-5-en-20-ols to functionalize C-18, followed by controlled opening of the epoxide ring by reagents chosen to give either 3β,16α,18- or 3β,16β,18-triacetoxy-17α-hydroxypregn-5-en-20-one. Reduction of the 20-oxo group and oxidative cleavage of the C(17)–C(20) bond produced the corresponding 3β,16,18-triacetoxyandrost-5-en-17-one. 3β,16α,18-Trihydroxyandrost-5-en-17-one was obtained by deacetylation of its triacetate, but the 16β-epimer rearranged on hydrolysis to give 3β,17β,18-trihydroxyandrost-5-en-16-one. The androst-5-ene-3β,16,17β,18-tetraols were, also prepared.