Microbial transformations of steroids--I. Rare transformations of progesterone by Apiocrea chrysosperma

When Apiocrea chrysosperma is incubated with progesterone for 7 days in a peptone, yeast-extract medium, eight major metabolites are produced. Each compound has been purified and its structure determined by high-field 1D and 2D 1H nuclear magnetic resonance (NMR) spectroscopy. A clear synthetic pattern is recognisable. The products have been formed by multiple transformation reactions, usually double hydroxylations. Seven compounds are tertiary alcohols in which the hydroxyl group is located on the underside of the progesterone skeleton at either the axial 9 alpha- or the axial 14 alpha-site. One compound has hydroxyl groups at both these sites. Five metabolites are also secondary progesterone alcohols, the hydroxyl groups being at the 6 beta-, 15 alpha- or 15 beta-sites. Two compounds are monohydroxy metabolites; one is dehydrogenated in ring B and the other has lost the pregnane side-chain. The structures of the eight metabolites are 6 beta, 9 alpha-dihydroxyprogesterone; 6 beta, 14 alpha-dihydroxyprogesterone; 9 alpha, 14 alpha-dihydroxyprogesterone; 9 alpha, 15 beta-dihydroxyprogesterone, 14 alpha, 15 alpha-dihydroxyprogesterone; 14 alpha, 15 beta-dihydroxyprogesterone; 14 alpha-hydroxypregna-4,6-diene-3,20-dione and 15 alpha-hydroxyandrostene-3,17-dione. All compounds, except the last one, are biologically rare because they are not products of mammalian progesterone or androstenedione metabolism. They would be difficult to synthesise chemically. We believe that the compounds, 9 alpha, 15 beta-dihydroxyprogesterone; 14 alpha, 15 alpha-dihydroxyprogesterone and 14 alpha-hydroxypregn-4,6-diene-3,20-dione, have not been reported previously as microbial transformation products of progesterone.