Microbial transformation of 3-hydroxy-5,6-cyclopropanocholestanes - An alternative route to 6-methylsteroids

Abstract

Incubation of 3β-hydroxy-5,6α-cyclopropano-5α-cholestane ( 4), 3β-hydroxy-5,6β-cyclopropano-5β-cholestane ( 5), and 3β-hydroxy-5,6α-cyclopropano-5α-cholest-7-ene ( 6) with Mycobacterium sp. (NRRL B-3805) gave a mixture of side chain cleaved 17-keto steroids as the major products in 52, 57, and 69% yields, respectively. Among these 17-keto steroids, the cyclopropyl ring eliminated product, androst-4-ene-3,17-dione ( 9), was isolated in 6, 4, and 8% yields, respectively. A cyclopropyl ring migration product, 6α,7α-cyclopropanoandrost-4-ene-3,17-dione ( 16), was isolated from the incubation mixture of 6 in 4% yield, also 10% yield of 16 was obtained when 5,6α-cyclopropano-5α-androst-7-ene-3,17-dione ( 12) was incubated. The cyclopropyl ring opening and subsequent reduction followed by oxidation of the two major biotransformation products, 5,6β-cyclopropano-5β-androsta-3,17-dione ( 10) and 5,6α-cyclopropano-5α-androsta-3,17-dione ( 7), gave 6β- and 6α-methylandrost-4-ene-3,17-dione in 60, and 45% yields, respectively.