Inhibitors of sterol synthesis. An efficient and specific side chain oxidation of 3β-hydroxy-5α-cholest-8 (14)-en-15-one. Facile access to its metabolites and analogs

Article abstract of DOI:10.1016/0040-4039(91)80590-3

Treatment of the acetate of 3β-hydroxy-5α-cholest-8(14)-en-15-one (1), a potent regulator of cholesterol metabolism, with a mixture of trifluoroacetic anthydride, hydrogen peroxide, and sulfuric acid at ～-2°C for 3.5 h gave remarkably high yields (～64%) of a mixture of C₂₄ oxygenated products: 3β-acetoxy-24-trifluoroacetoxy-5α-chol-8(14)-en-15-one (6), 3-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one (7), and 3β,24-diacetoxy-5α-chol-8(14)-en-15-one (8). Selective hydrolysis of the trifluoroacetoxy function of 6 in the crude reaction product gave isolated yields of 7 and 8 of 61% and 3%, respectively. The availability of 7, selectively protected at C-3, provides a key intermediate for the synthesis of potential metabolites and analogs of 1. Thus, 7 was readily converted to 3β-hydroxy-15-keto-5α-chol-8(14)-en-24-oic acid (4) and the 25-aza analog of l, 3βhydroxy-24-dimethylamino-5α-chol-8(14)-en-15-one (10).