Described herein are the chemical syntheses of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one from diosgenin and the examinations of their ability to inhibit the cholesteryl ester transfer protein (CETP). Clemmensen reduction of diosgenin gave cholest-5-ene-3 beta, 16 beta,26-triol. Tosylation of the latter compound gave cholest-5-ene-3 beta,16 beta,26-triol 26-tosylate which, upon reduction with LiAIH4, gave cholest-5-ene-3 beta,16 beta-diol. Hydrogenation-benzoylation of the latter to 5 alpha-cholest-3 beta,16 beta-diol 3 beta-benzoate followed by mesylation-elimination gave 5 alpha-cholest-16-ene-3 beta-ol 3 beta-benzoate. Controlled oxidation of the latter with CrO3-dimethylpyrazole gave 3 beta-hydroxy-5 alpha, 14 alpha-cholest-16-en-15-one 3 beta-benzoate. Oxidation of delta 16-15-one with SeO2 gave 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one 3 beta-benzoate along with 3 beta-hydroxy-5 alpha, 14 beta-cholest-16-en-15-one 3 beta-benzoate. Selective hydrogenation of the delta 8(14),16-15-ketosteryl ester, followed by base hydrolysis gave 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one. Hydrolysis of 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one 3 beta-benzoate in basic media gave 3 beta-hydroxy-5 alpha-cholest-8(14),16-dien-15-one. The effects of the 15-ketosterols on the CETP activity were studied in vitro by incubating cholesteryl ester donor (HDL), cholesteryl ester acceptor (LDL) and human plasma as a CETP source at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)