Inhibitors of sterol synthesis. Characterization of side chain oxygenated derivatives formed upon incubation of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one with rat liver mitochondria

Abstract

3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent inhibitor of sterol biosynthesis, was incubated with rat liver mitochondrial preparations in the presence of NADPH. The following four major products were isolated and characterized by nuclear magnetic resonance and mass spectrometry: (25R)- and (25S)-3 beta,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one (4:1 ratio), 3 beta-hydroxy-15-oxo-5 alpha-cholest-8(14)-en-26-oic acid, and 3 beta,25-dihydroxy-5 alpha-cholest-8(14)-en-15-one. In addition, 3 alpha,26-dihydroxy-5 alpha-cholest-8(14)-en-15-one and 3 beta,24-dihydroxy-5 alpha-cholest-8(14)-en-15-one were identified as minor products by capillary gas chromatography-mass spectrometry.