Alkylated steroids. Part 1. 16α-Substituted 17α-methylpregnanes

Abstract

The sequential reaction of 3β-acetoxypregna-5,16-dien-20-one (1) with methylmagnesium bromide and then methyl iodide has been examined in detail. The major product (85%) was 3β-hydroxy-16α,17α-dimethylpregn-5-en-20-one (2). Other products identified were 3β-hydroxy-16α-methylpregn-5-en-20-one (4); the 21-methyl derivatives [(5) and (10)] of (2) and (4); the 21-(1-hydroxy-1-methylethyl) derivative (11) of (2); and a trace of the 21,21-dimethyl derivative (12) of (2). The scope of the reaction with regard to the range of substituents that can be introduced at positions 16 and 17 has been established by preparing a series of 16α-substituted 17α-methylpregnenolones with a variety of alkyl, aryl, and aralkyl groups. Some of these have been converted into the corresponding 16α,17α-disubstituted progesterones.