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

George J. Schroepfer, Rice University
Edward J. Parish, Rice University
Gary L. Gilliland, Rice University
Marcia E. Newcomer, Rice University
Laura L. Sommerville, Rice University
Florante A. Quiocho, Rice University
Andrew A. Kandutsch, Rice University

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. © 1978.