Enantioselective synthesis of the key intermediate of the acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor (R-106578) using 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-Ru(OAc)2 as a catalyst.
Acidic segment of an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, R-106578 was synthesized by enantioselective hydrogenation of the Z-olefine (9-(Z)) using (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-Ru(OAc)2 as a catalyst in methanol at 100 degrees C, 5 kgf/cm2 of H2 pressure. The requisite Z-olefine was prepared regioselectively via coumarin derivative (5).
Murakami
M
M
Process Development Laboratories, Sankyo Co., Ltd., Kanagawa, Japan.
Kobayashi
K
K
Hirai
K
K
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
C419450:2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru(OAc)2; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D002785:Sterol O-Acyltransferase