title: Inhibitors of sterol synthesis: 3 beta-hydroxy-25,26,26,26,27,27,27- heptafluoro-5 alpha-cholestan-15-one, an analog of a potent hypocholesterolemic agent in which its major metabolism is blocked.
abstract: The chemical synthesis of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro- 5 alpha-cholestan-15-one (IV) has been pursued to provide an analog of the potent hypocholesterolemic agent 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) in which its major metabolism is blocked. Reduction of 3 beta-acetoxy-5 alpha-chola-8(14),23-dien-15-one with lithium in liquid ammonia gave 3 beta-hydroxy-5 alpha-chol-23-en-15-one (VI). Addition of (CF3)2CFI to VI in the presence of triethylborane gave 3 beta-hydroxy-23R-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan- 15-one, which was reduced to IV with tributyltin hydride. IV was found to be highly active in lowering the levels of HMG-CoA reductase activity in CHO-K1 cells, in lowering acyl coenzyme A:cholesterol acyltransferase activity in jejunal microsomes, and in lowering serum cholesterol levels in rats.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251.
authors.forename: S
authors.initials: S
authors.lastname: Swaminathan
authors.forename: A U
authors.initials: AU
authors.lastname: Siddiqui
authors.forename: F D
authors.initials: FD
authors.lastname: Pinkerton
authors.forename: N
authors.initials: N
authors.lastname: Gerst
authors.forename: W K
authors.initials: WK
authors.lastname: Wilson
authors.forename: G J
authors.initials: GJ
authors.lastname: Schroepfer
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents; D016466:CHO Cells; D002778:Cholestanones / Q000494:pharmacology*; D006224:Cricetinae; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D007583:Jejunum / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
chemical_list: D000924:Anticholesteremic Agents; D002778:Cholestanones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002785:Sterol O-Acyltransferase