15 beta-Methyl-5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol. Synthesis, structure, and inhibition of sterol synthesis in animal cells.
Treatment of 3 beta-benzoyloxy-14 alpha,15 alpha-epoxy-5 alpha-cholest-7-ene with methyl magnesium iodide gave, as the major product, 15 beta-methyl-5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol. The product was characterized as the free sterol and in the form of its 3 beta-acetoxy and 3 beta-p-bromobenzoate derivatives. Unambiguous assignment of structure was based upon X-ray analysis of the latter derivative. 15 beta-Methyl-5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol was found to be a potent inhibitor of sterol synthesis in cultured mammalian cells. The 15 beta-methyl-3 beta,15 alpha-dihydroxysterol caused a 50% reduction of the level of HMG-CoA reductase activity and a 50% reduction in the incorporation of labeled acetate into digitonin-precipitable sterols in L cells at a concentration of 3.0 x 10(-6) M.
Department of Biochemistry, Rice University, Houston, Texas 77001.
G J
GJ
Schroepfer
E J
EJ
Parish
A A
AA
Kandutsch
S T
ST
Bowen
F A
FA
Quiocho
D000818:Animals; D002782:Cholestenes / Q000138:chemical synthesis* / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007202:Indicators and Reagents; D007739:L Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013261:Sterols / Q000096:biosynthesis*; D014961:X-Ray Diffraction
D002782:Cholestenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007202:Indicators and Reagents; D013261:Sterols; C054713:15-methylcholest-7-ene-3,15-diol