Abstract
27-Nor-24, 25-dihydrolanosterol (27-nor-DHL), 26, 27-dinor-24, 25-dihydrolanosterol (26, 27-dinor-DHL), and 25, 26, 27-trinor-24, 25-dihydrolanosterol (25, 26, 27-trinor-DHL), analogs of 24, 25-dihydrolanosterol (DHL) which have no C-27 carbon, C-26, 27 carbons and C-25, 26, 27 carbons, were converted to the corresponding 14-demethylated products using a reconstituted monooxygenase system from rat liver microsomes which contained cytochrome P-45014DM catalyzing lanosterol 14-demethylation and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase in the presence of NADPH and molecular oxygen. Each metabolite showed a relative retention time (RtR)of 0.72 with respect to each substrate in high-performance liquid chromatography (HPLC) on a reversed-phase column. Comparison of each gas chromatography-mass spectrum and RtR value with those of the metabolite of DHL, 4, 4-dimethyl-5α-cholesta-8, 14-dien-3β-ol, indicated that the metabolites could be inferred to be 27-nor-4, 4-dimethyl-5α-cholesta-8, 14-dien-3β-ol, 26, 27-dinor-4, 4-dimethyl-5α-cholesta-8, 14-dien-3β-ol, and 25, 26, 27-trinor-4, 4-dimethyl-5α-cholesta-8, 14-dien-3β-ol. However, 24, 25, 26, 27-tetranor- and 23, 24, 25, 26, 27-pentanor analogs of DHL and 20-iso-24, 25-dihydrolanosterol were not metabolized by the reconstituted enzyme system.
