7α,15β-Dichloro-5α-cholest-8(14)-en-3β-ol, a novel inhibitor of sterol biosynthesis in animal cells

Abstract

7α,15β-Dichloro-5α-cholest-8(14)-en-3β-ol has been prepared by controlled lithium aluminum hydride reduction of 3β-benzoyloxy-7α,15β-dichloro-5α-cholest-8(14)-ene. The latter compound was prepared by treatment of 3β-benzoyloxy-14α,15α-epoxy-5α-cholest-7-ene with gaseous HCl in chloroform at −40°. The structure of the dichloro compound was unequivocally established by X-ray crystallographic analysis of the 3β- p-bromobenzoate derivative. 7α,15β-Dichloro-5α-cholest-8(14)-en-3β-ol was found to be a potent inhibitor of sterol synthesis in animal cells in culture. The dichlorosterol caused a 50% reduction of the level of HMG-CoA reductase in L cells in culture at a concentration of 6 × 10 −7 M and a 50% inhibition of the synthesis of digitonin-precipitable sterols from labeled acetate in the same cells at a concentration of 2 × 10 −6 M.