Synthesis of hydroxylated steroid hormones via conjugate addition of a silyl-cuprate reagent.
The synthesis of several hydroxylated steroids via conjugate addition of Fleming's silyl-cuprate reagent, (PhMe2Si)2CuLi, a masked hydroxyl group, to the appropriate enone was studied. By this means 7 alpha-hydroxytestosterone (7) was obtained in good yield from 17 beta-hydroxyandrosta-4,6-dien-3-one (1a), though similar reactions on 17 beta-hydroxyandrosta-1,4-dien-3-one (8) gave a low yield of 1 alpha-hydroxytestosterone (13) chiefly through the poor conversion of the phenylsilyl intermediate into the halogenosilane. 3 beta,16 alpha-Dihydroxy-5 alpha-pregnan-20-one (18b) was obtained in a similar manner from 3 beta-hydroxy-5 alpha-pregn-16-en-20-one and 5 alpha-cholestane-1 alpha,3 alpha-diol(17) was produced from the 1-en-3-one (14) via conjugate addition of the silyl group, reduction of the carbonyl function, and oxidative removal of the silyl group.
Garside
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D
Department of Chemistry, Queen Mary and Westfield College, London, UK.
Kirk
D N
DN
Waldron
N M
NM
D000736:Androstenes / Q000138:chemical synthesis; D004083:Cholestanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D003300:Copper / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013739:Testosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000736:Androstenes; D013739:Testosterone; D003300:Copper; D004083:Cholestanol; D011280:Pregnanolone