Influence of a 9-double bond on stereospecific microbial 4,5-reductions - Schubert, K.; Schumann, G.; Kaufmann, G. (Elsevier)
By stereospecific microbial reduction with Rhodosporidium rubrum or Rhodotorula glutinis, 17α-cyanomethyl-4-estren-17β-ol-3-one was metabolized to 17α-cyanomethyl-5α-estrane-3β,17β-diol (50%) and 17α-cyanomethyl-5α-estrane-3α,17β-diol (30%). By Clostridium paraputrificum the same substrate was reduced stereospecifically to 17α-cyanomethyl-5β-estrane-3α,17β-diol (70%). When the corresponding 9-dehydrogenated compound 17α-eyanomethyl-4,9-estradien-17β-ol-3-one (STS 557, a new progestagen) was fermented, yeasts failed in 5α-reducing the 4-double bond. Still Clostridium paraputrificum formed the expected 5β-reduced metabolite 17α-cyanomethyl-5β-estr-9-ene-3α,17β-diol (60%). Structures were elucidated by n.m.r. and mass spectra and partly by circular dichroism. By oxidation of the metabolites, the corresponding 3-oxo compounds 17α-cyanomethyl-5α-estran-17β-ol-3-one, 17α-cyanomethyl-5β-estran-17β-ol-3-one and 17α-cyanomethyl-5β-estr-9-en-17β-ol-3-one were prepared. The evident influence of the 9-double bond on reduction of the 4-en-3-oxo compound STS 557 preventing 5α-reduction but permitting 5β-reduction is discussed in view of the distinctly diminished metabolism of this progestagen in mammals.
http://linkinghub.elsevier.com/retrieve/pii/0022-4731(83)90333-3
Keywords: W; V