Epoxidation and reduction of cholesterol, 1,4,6-cholestatrien-3-one and 4,6-cholestadien-3β-ol

Many naturally occurring polyhydroxylated sterols and oxysterols exhibit potent biologic activities. This paper describes reagent and position selectivity of epoxidation and reduction of cholesterol derivatives. Cholesterol was reacted with in-chloroperoxybenzoic acid (m-CPBA) to form 5 alpha,6 alpha-epoxycholestan-3 beta-ol, but in reaction with 30% H2O2, it did not reacted. 1,4,6-Cholestatrien-3-one was obtained from cholesterol and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. 1,4,6-Cholestatrien-3-one was reacted with 30% H2O2 and 5% NaOH in methanol to give 1 alpha,2 alpha-epoxy-4,6-cholestadien-3-one, which was stereoselectively reduced with NaBH4 to form 1 alpha,2 alpha-epoxy-4,6-cholestadien-3 beta-ol and reduced with Li metal in absolute ethanol to give 2-ethoxy-1,4,6-cholestatrien-3-one. And 1,4,6-cholestatrien-3-one was epoxidized with m-CPBA in dichloromethane to afford 6 alpha,7 alpha-epoxy-1,4-cholestadien-3-one, which was reacted with NaBH4 to synthesize 6 alpha-hydroxy-4cholesten-3-one and reduced Li metal in absolute ethanol to form 2-ethoxy-1,4,6-cholestatrien-3-one, respectively. 1,4,6-Cholestatrien-3-one was reduced with NaBH4 in absolute ethanol to form 4,6-cholestadien-3 beta-ol, which was reacted with 30% H2O2 to leave original compound, but was reacted with in-CPBA to give 4 beta,5 beta-epoxy-6-cholesten-3 beta-ol as the major product and 4 beta,5 beta-epoxy-6 alpha,7 alpha-epoxycholestan-3 beta-ol as the minor product. (c) 2005 Published by Elsevier Inc.