Inhibitors of sterol synthesis. Chemical synthesis of 5 beta-cholest-8-ene-3 beta,15 alpha-diol and its effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells.
5 beta-Cholest-8-ene-3 beta,15 alpha-diol, prepared by hydroboration of 5 beta-cholesta-8,14-dien-3 beta-ol, was determined to have the 14 alpha-H,15 alpha-OH configuration by comparisons of observed and calculated lanthanide-induced shifts for the 3-tertbutyldimethylsilyl derivative. The 3 beta,15 alpha-diol was found to exist partially in a conformation in which ring B is a 5 beta, 6 alpha-half chair and the axial-equatorial orientation of ring A substituents is reversed. This conformation has been observed previously for 3 beta-(p-bromobenzoyloxy)-5 beta-cholesta-8,14-diene and for some cis-decalin derivatives. 5 beta-Cholest-8-ene-3 beta,15 alpha-diol was found to be highly active in the lowering of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Chinese hamster ovary cells and only slightly less active than the corresponding sterol (5 alpha-cholest-8-ene-3 beta,15 alpha-diol) with the trans A-B ring junction.
Wilson
W K
WK
Department of Biochemistry, Rice University, Houston, TX 77251.
Pinkerton
F D
FD
Kirkpatrick
N D
ND
Schroepfer
G J
GJ
D002460:Cell Line; D002782:Cholestenes / Q000138:chemical synthesis* / Q000494:pharmacology; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010053:Ovary; D013056:Spectrophotometry, Ultraviolet; D013261:Sterols / Q000378:metabolism*
D002782:Cholestenes; D013261:Sterols; C061276:cholest-8-ene-3,15-diol; D006903:Hydroxymethylglutaryl CoA Reductases