New metabolites from fungal biotransformation of an oral contraceptive agent: methyloestrenolone.

Fungal cell cultures were used for the first time for the biotransformation of methyloestrenolone (1), an oral contraceptive. Fermentation of 1 with Macrophomina phaseolina, Aspergillus niger, Gibberella fujikuroi, and Cunninghamella echinulata produced eleven metabolites 2-12, six of which 2-5, 11 and 12 were found to be new. These metabolites were resulted from the hydroxylation at C-1, C-2, C-6, C-10, C-11, and C-17α-CH3, as well as aromatization of ring A of the steroidal skeleton of substrate 1. The transformed products were identified as 17α-methyl-6β,17β-dihydroxyestr-4-en-3-one (2), 17α-(hydroxymethyl)-11β,17β-dihydroxyestr-4-en-3-one (3), 17α-methyl-2α,11β,17β-trihydroxyestr-4-en-3-one (4), 17α-methyl-1β,17β-dihydroxyestr-4-en-3-one (5), 17α-methyl-11α,17β-dihydroxyestr-4-en-3-one (6), 17α-methyl-11β,17β-dihydroxyestr-4-en-3-one (7), 17α-methyl-10β,17β-dihydroxyestr-4-en-3-one (8), 17α-(hydroxymethyl)-17β-hydroxyestr-4-en-3-one (9), 17α-methylestr-1,3,5(10)-trien-3,17β-diol (10), 17α-methyl-3,17β-dihydroxyestr-1,3,5(10)-trien-6-one (11), and 17α-methyl-6β,10β,17β-trihydroxyestr-4-en-3-one (12).