Smith K E, Latif S, Kirk D N, White K A
School of Biological Sciences, Queen Mary College (University of London), England.
J Steroid Biochem. 1988 Jul;31(1):83-9. doi: 10.1016/0022-4731(88)90209-9.
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.
当金黄蜂海绵（Apiocrea chrysosperma）在蛋白胨酵母提取物培养基中与孕酮一起孵育7天时，会产生8种主要代谢产物。每种化合物都已被纯化，其结构通过高场一维和二维氢核磁共振（NMR）光谱确定。可以识别出清晰的合成模式。这些产物是通过多个转化反应形成的，通常是双羟基化反应。7种化合物是叔醇，其中羟基位于孕酮骨架下方的轴向9α-或轴向14α-位。一种化合物在这两个位置都有羟基。5种代谢产物也是孕酮仲醇，羟基位于6β-、15α-或15β-位。两种化合物是单羟基代谢产物；一种在B环脱氢，另一种失去了孕烷侧链。这8种代谢产物的结构分别是6β,9α-二羟基孕酮；6β,14α-二羟基孕酮；9α,14α-二羟基孕酮；9α,15β-二羟基孕酮，14α,15α-二羟基孕酮；14α,15β-二羟基孕酮；14α-羟基孕-4,6-二烯-3,20-二酮和15α-羟基雄烯-3,17-二酮。除最后一种化合物外，所有化合物在生物学上都很罕见，因为它们不是哺乳动物孕酮或雄烯二酮代谢的产物。它们很难通过化学方法合成。我们认为，9α,15β-二羟基孕酮；14α,15α-二羟基孕酮和14α-羟基孕-4,6-二烯-3,20-二酮作为孕酮的微生物转化产物此前尚未见报道。
