New 3-substituted Delta 8(14)-15-ketosterols. Chemical synthesis and effects on cholesterol biosynthesis in Hep G2 cells.

5 alpha-Cholest-8(14)-en-15-ones with 3 beta-substitutents including 2-prop enyloxy-, 2(R,S)-2,3-oxidopropyloxy-, 2(R,S)-2,3-dihydroxypropyloxy-, 2-oxo ethoxy-, 2(R,S)-2-acetoxy-3-acetamido-propyloxy-, 2(R,S)-2-hydroxy-3-acetam idopropyloxy-, 2(R,S)-2-hydroxy-3(7-nitrobenzo-2-oxa-1.3-diazol-4-ylamino)p ropyloxy-, 2(R,S),2-hydroxy-3(5-dimethylaminonaphtalenesulfonylamido)propyo xy were synthesized. 3 beta-(2-propenyloxy)-5 alpha-cholesta-7, 14-diene wa s first prepared from 5 alpha-cholesta-7, 14-dien-3 beta-ol and then transf ormed to 3 beta-(2-propenyloxy)-5 alpha-cholest-8(14)-en-15one by selective 14 alpha, 15 alpha-epoxidation followed by acid-catalyzed isomerization. T he allyl double bond in 3 beta-(2-propenyloxyl-5 alpha-cholest-8(14)-en- 15 -one was epoxidized with m-chloroperbenzoic acid for conversion to target p roducts. Cytotoxicity of titled compounds as well as their effects on chole sterol biosynthesis were evaluated in human hepatoma Hep G2 cells.