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

The Preparation of 21,21-Dimethylprogesterone

“…4,5 This was followed by quenching the anion with methyl iodide. 4,5 This was followed by quenching the anion with methyl iodide.…”

“…There has been relatively little interest in the C-21 alkylation of progesterone since early studies 2 with the homologues of progesterone, 21-methyl and 21-ethylprogesterone, showed that they had little progestational activity on the proliferation of the endometrium of test aninlals. Subsequent studies [3][4][5] have concentrated on the preparation of 17α-alkyl and 16α, 17α -dialkylpregnanes in which 21-methylated pregnanes were unwanted by-products. However, a 19-nor-steroid promegestone, 17α, 21dimethyl-19-norpregna-4,9-diene-3, 20-dione, 6 has attracted interest because it binds to the progestin receptor.…”

“…The alkylation at C-17 was achieved by the generation of the intermediate 17-enolate anion through reduction of a 16dehydropregn-20-one 3 or by the conjugate addition of methylmagnesium halide to the unsaturated ketone. 4,5 This was followed by quenching the anion with methyl iodide. The higher homologues of progesterone were prepared 2 by a malonic ester synthesis from the 20-carboxylic acid chloride.…”