INHIBITORS OF STEROL SYNTHESIS - AN IMPROVED CHEMICAL SYNTHESIS OF 26-OXYGENATED DELTA(8(14))-15-KETOSTEROLS HAVING THE 25R CONFIGURATION

(25R)-3 beta,26-Dihydroxy-5 alpha-cholest-8(14)-en-15-one (I) was synt hesized in four steps from (25R)-3 beta,26-diacetoxycholesta-5,7-diene (III) in 30% overall yield. Isomerization of III with HCl in chlorofo rm-dichloromethane at -60 degrees C gave (25R)-3 beta,26-diacetoxy-5 a lpha-cholesta-7,14-diene together with the 5 alpha-Delta(8.14) and 5 b eta-Delta(8.14) isomers in a 5:1:1 ratio. Epoxidation of the crude die ne mixture with m-chloroperbenzoic acid, followed by hydrolysis in ace tone containing concentrated HClO4 (0.1%) gave (25R)-3 beta,26-diaceto xy-5 alpha-cholest-8(14)-en-15-one (VIII), accompanied by numerous min or byproducts, including the 5 alpha,14 beta-Delta(7), 5 alpha, 14 bet a-Delta(8) and 5 beta,14 beta-Delta(8) isomers of VIII. All four 15-ke tosterol esters were isolated by chromatography and fully characterize d by mass spectrometry and H-1 and C-13 nuclear magnetic resonance. Tr eatment of VIII with potassium carbonate in degassed methanol gave I.