Inhibitors of sterol synthesis. Chemical synthesis and spectral properties of (25R)-5 alpha-cholest-8(14)-ene-3 beta,15 beta,26-triol, a potential metabolite of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and its effects on 3-hydroxy-3-methylglutaryl-coenzyme A reductase in CHO-K1 cells.
(25R)-5 alpha-Cholest-8(14)-ene-3 beta,15 beta,26-triol (III) was prepared by reduction of (25R)-3 beta,26-diacetoxy-5 alpha-cholest-8(14)-en-15-one with sodium borohydride followed by treatment of the crude product with lithium aluminium hydride. The trihydroxysterol III, a potential metabolite of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one, was characterized by the results of mass spectral studies and by nuclear magnetic resonance (NMR) spectroscopy. Full 1H and 13C NMR assignments for III and 5 alpha-cholest-8(14)-ene-3 beta,15 beta-diol are given and used to establish the structure of III. The triol was found to be very potent in lowering the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Chinese hamster ovary cells.
Swaminathan
S
S
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892.
Pinkerton
F D
FD
Wilson
W K
WK
Schroepfer
G J
GJ
D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002783:Cholestenones / Q000378:metabolism*; D006224:Cricetinae; D006888:Hydroxycholesterols / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D013261:Sterols / Q000096:biosynthesis*
D002783:Cholestenones; D006888:Hydroxycholesterols; D013261:Sterols; C076785:cholest-8(14)-ene-3,15,26-triol; C015073:cholest-8(14)-en-3-ol-15-one; D006903:Hydroxymethylglutaryl CoA Reductases