A STEREOSELECTIVE SYNTHESIS OF 7-BETA-PHENYL AND 7-BETA-METHYLCHOLESTEROL

A stereoselective synthesis of 7beta-phenylcholesterol and 7beta-methylcholesterol is described. Cholesterol is an immensely important biological molecule. Its biosynthesis,1 conversion to steroid hormones2,3 and even its intracellular esterification4 (cholesterol acyltransferase, ACAT) form important areas of research. Cholesterol is metabolized in the body to bile acids in which the rate limiting step is the conversion of cholesterol to 7alpha-hydroxycholesterol by the enzyme 7alpha-hydroxylase. 5 Substituents of cholesterol at the 7 position should metabolically stabilize the molecule. 7Alpha-substituted steroids are conveniently prepared and have shown interesting antiprogestational,6 antiestrogen,7 antiandrogen,8 aldosterone antagonist9 and aromatase8 inhibitory activities. Chemistry for the stereoselective synthesis of 7beta-substituted steroids is relatively less developed.10 In this paper, we report a new stereoselective synthesis of 7beta-phenyl and 7beta-methylcholesterol. Chemistry described here should be applicable to the preparation of other 7beta-substituted steroids.