Potassium Hydroxide → (3beta,5beta,15alpha,16alpha)-15,16-Dihydro-3,5-dihydroxy-3'H-cycloprop(15,16)androsta-6,15-dien-17-one

Participants

Reaction Steps

The starting material of the process is 3β-hydroxy-15β,16β-methyleneandrost-5-en-17-one. The hydroxy in 7β position is introduced in a fermentation process using Botryodiplodia malorum, the resultant compound is acetylated in a regioselective manner with pivalic anhydride in the presence of 4-dimethylaminopyridine yielding the corresponding 3β-pivaloyloxy derivative. Said pivaloyloxy derivative was reacted with tert-butyl hydroperoxide in the presence of VO (acetonylacetonate)2 catalyst to give the 5β,6β-epoxy derivative which, in turn, was reacted with triphenylphosphine and carbon tetrachloride in dichloromethane to yield the 7α-chloro derivative. Said 7α-chloro derivative was reacted with zinc in a mixture of acetic acid and tetrahydrofuran yielding the 5β-hydroxy-15β,16β-methylene-3β-pivaloyloxyandrost-6-en-17-one which then was hydrolyzed with potassium hydroxide to give 3β,5β-dihydroxy-15β,16β-methyleneandrost-6-en-17-one.

Provenance & Evidence