The synthesis of some cholesterol derivatives as probes for mechanisms of cholesterol metabolism

Abstract

The syntheses of a series of cyclopropa[5,6]cholestanes, difluorocholestanes, and a ring B azacholestenone are described. Cyclopropa[5,6]cholestane-3,7-diols and their oxo derivatives were prepared from 3β-acetoxy-5α-cholest-5-en-7-one and a new route to 5α,6α-cyclopropa[5,6]cholestan-3β-ol was developed. 7,7-and 6,6-Difluorocholestan-3-ols were obtained from fluorination of the acetoxy ketone precursors with sulphur tetrafluoride. 3β-Hydroxy-6-azacholest-4-en-7-one was prepared via the 3β-acetate by ozonolysis and ammonolysis of 3β-acetoxy-5α-cholest-4-en-7-one. The products have been used to study the mechanism of oxidation of cholest-5-en-3β-ol by its 7α-hydroxylase.