Inhibition of sterol biosynthesis by 9α-fluoro and 9α-hydroxy derivatives of 5α-cholest-8(14)-en-3β-ol-15-one

Abstract

5α-Cholest-8(14)-en-3β,9α-diol-15-one has been prepared by chemical synthesis in two steps from 5α-cholest-8(14)-en-3β-ol-15-one. 9α-Fluoro-5α-cholest-8(14)-en-3β-ol-15-one was prepared in 91% yield from the corresponding 9α-hydroxysterol. 9α-Fluoro-5α-cholest-8(14)-en-3,15-dione was prepared, in 84% yield, from the corresponding 3β-hydroxy compound. These compounds have been found to be potent inhibitors of sterol synthesis in animal cells in culture. The concentrations of the steroids required to cause a 50% inhibition of the synthesis of digitonin-precipitable sterols from labeled acetate were comparable to those required to cause a 50% reduction in the levels of HMG-CoA reductase activity in the same cells.