Microbial transformation of 17α-ethynyl- and 17α-ethylsteroids, and tyrosinase inhibitory activity of transformed products

The microbial transformation of the 17α-ethynyl-17β-hydroxyandrost-4-en-3-one (1) (ethisterone) and 17α-ethyl-17β-hydroxyandrost-4-en-3-one (2) by the fungi Cephalosporium aphidicola and Cunninghamella elegans were investigated. Incubation of compound 1 with C. aphidicola afforded oxidized derivative, 17α-ethynyl-17β-hydroxyandrosta-1,4-dien-3-one (3), while with C. elegans afforded a new hydroxy derivative, 17α-ethynyl-11α,17β-dihydroxyandrost-4-en-3-one (4). On the other hand, the incubation of compound 2 with the fungus C. aphidicola afforded 17α-ethyl-17β-hydroxyandrosta-1,4-dien-3-one (5). Two new hydroxylated derivatives, 17α-ethyl-11α,17β-dihydroxyandrost-4-en-3-one (6) and 17α-ethyl-6α,17β-dihydroxy-5α-androstan-3-one (7) were obtained from the incubation of compound 2 with C. elegans. Compounds 1-6 exhibited tyrosinase inhibitory activity, with compound 6 being the most potent member (IC50 = 1.72 μM).