Synthesis of C-17 Epimeric 5α, 13α-Pregnan-20-ones

Abstract

The titled compounds have been synthesized from 13α-dehydroepiandrosterone (I) as outlined in Chart 1. The Grignard reaction of I with ethynylmagnesium bromide gave two epimeric 17-ethynyl-17-ols (IIa, VIIa), which on hydration were led to 17-hydroxy-13α-pregn-5-en-20-ones (IIIa, VIIIa), respectively. On catalytic hydrogenation these 5-dehydro compounds were transformed into the 5α-saturated derivatives (IIIc, VIIIc). The metal hydride reduction, usual acetylation followed by the Serini reaction afforded C-17 epimeric 3β-acetoxy-5α, 13α-androstane-3β, 17-diol diacetates (VI, XIb) employing the Baeyer-Villiger reaction. In the analogous manner IIIa and VIIIa were converted into the corresponding 13α-pregn-5-en-20-ones (Va, Xa).