Steroids derived from fusidic acid. Part 2. Synthesis of an 8α, 14β-dimethyl-18-norandrostane. A revised mechanism

Abstract

An improved synthesis of 3α-acetoxy-4α,8α,14β-trimethyl-18-norandrostan-17-one (15) from fusidic acid is described. Ruthenium tetraoxide is compared with ozone as a means of cleaving the side-chain. The thermal stability of the resulting androstanone (8) and its reactions with pyridine, acetic acid, and zinc in acetic acid is outlined. Evidence is presented for a trans-β-elimination of the 11 α-acetoxy-group from (8) and the formation of a transient Δ^9,(11)-androstene (19). This mechanism contrasts with that previously suggested and questions the chemical basis for the stereochemistry previously assigned to C-9.