Reaction of cholesterol 5,6-epoxides with simulated gastric juice

Cholesterol 5 alpha,6 alpha-epoxide (alpha-epoxide) and cholesterol 5 beta,6 beta-epoxide (beta-epoxide) were individually suspended in simulated gastric juice (pH 1.2) at 37 C, and their reaction was followed by gradient high performance liquid chromatography (HPLC) with flame ionization (FID) detection. Both epoxides reacted rapidly in the aqueous acid medium. The alpha-epoxide formed 6 beta-chlorocholestane-3 beta,5 alpha-diol (alpha-chlorohydrin) and 5 alpha-cholestane-3 beta,5,6 beta-triol (triol), while the beta-epoxide formed 5 alpha-chlorocholestane-3 beta,6 beta-diol (beta-chlorohydrin) and triol. The isomeric chlorohydrins reacted further to form the triol. In mildly alkaline aqueous medium, each chlorohydrin reverted to the epoxide from which it was formed. The data suggest that both epoxides, which have been reported to have adverse health effects in animals, would be largely hydrolyzed in the stomach and to the triol, which also has been reported to have biological activity. The data further suggest that residual chlorohydrins surviving stomach residence can be expected to revert to epoxide in the more alkaline intestinal environment.