1. Synthesis of hydroxylated steroid hormones via conjugate addition of a silyl-cuprate reagent
- Author
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David N. Kirk, Diana Garside, and Norman M. Waldron
- Subjects
Pharmacology ,Magnetic Resonance Spectroscopy ,Silylation ,Metalation ,medicine.medical_treatment ,Organic Chemistry ,Clinical Biochemistry ,Pregnanolone ,Biochemistry ,Steroid ,Cholestanol ,Hydroxylation ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Reagent ,Yield (chemistry) ,medicine ,Organic chemistry ,Androstenes ,Testosterone ,Molecular Biology ,Enone ,Copper ,Conjugate - Abstract
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.
- Published
- 1994
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