Alkylated steroids. Part 5. Formation of 17β-acetylenic steroids from hindered 20-oxo-compounds via Grignard derived enolates

Abstract

Treatment of methyl 3β-acetoxy-16α,17α-dimethyl-5α-androst-9(11)-ene-l7-carboxylic acid (1), or 3β-hydroxy-16α,17α-dimethyl-5α-pregn-9(11)-en-20-one (4), with methylmagnesium halide in refluxing anisole gives the 20-yne (3). Similarly 3β-acetoxy-16α,17α-dimethylpregn-5-en-20-one (5) gives the 20-yne (6). The mechanism of the reaction is discussed in terms of the steric hindrance due to the 16- and 17-methyl groups. Acetylenes (3) and (6) are converted into compounds of potential pharmacological interest.