Highly Regioselective and Stereoselective Biohydroxylations of Oxandrolone

Microbially catalyzed reactions are a powerful and valuable tool for organic synthesis of many compounds with potential biological activity. Herein, we report efficient hydroxylations of the steroidal anabolic-androgenic lactone, oxandrolone, in the cultures of three strains of fungi, Fusarium culmorum, Mortierella isabellina, and Laetiporus sulphureus. These reactions resulted in the production of four metabolites identified as 12β-hydroxyoxandrolone (2), 9α-hydroxyoxandrolone (3), 6α-hydroxyoxandrolone (4), and 15α-hydroxyoxandrolone (5), the latter being a new compound. The high substrate conversion rates and the product yields achieved indicate that these strains offer a new way to generate steroidal hydroxylactones with potential pharmaceutical interest. The structures of the isolated derivatives were characterized on the basis of spectroscopic data. The effect of modification of the A-ring structure of the steroid by the lactone group on the selectivity of hydroxylation in cultures of the tested fungi is also discussed.