7α,15β-Dichloro-5α-cholest-8(14)-en-3β-ol, a novel inhibitor of sterol biosynthesis in animal cells
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.
Publication Source (Journal or Book title)
Biochemical and Biophysical Research Communications
Schroepfer, G., Parish, E., Gilliland, G., Newcomer, M., Sommerville, L., Quiocho, F., & Kandutsch, A. (1978). 7α,15β-Dichloro-5α-cholest-8(14)-en-3β-ol, a novel inhibitor of sterol biosynthesis in animal cells. Biochemical and Biophysical Research Communications, 84 (3), 823-829. https://doi.org/10.1016/0006-291X(78)90778-7