The class
A multi-step synthesis from diosgenin yields two novel cholest-15-one steroids tested for CETP-inhibiting activity (Bioorg Med Chem 1995)
Original title: Chemical synthesis of 15-ketosterols and their inhibitions of cholesteryl ester transfer protein
This paper describes the chemical synthesis of two novel steroids, 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one and 3beta-hydroxy-5alpha-cholest-8(14),16-dien-15-one, starting from diosgenin through a multi-step sequence involving Clemmensen reduction, tosylation, lithium aluminum hydride reduction, hydrogenation-benzoylation, mesylation-elimination, and controlled oxidation with CrO3-dimethylpyrazole and SeO2. The resulting 15-ketosterols were evaluated for their ability to inhibit CETP activity, tested in vitro by incubating cholesteryl ester donor HDL, cholesteryl ester acceptor LDL, and human plasma as the CETP source at 37 degrees C. The published abstract is truncated before reporting the quantitative inhibition results.
Original abstract
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)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.