Formal synthesis of the ACE inhibitor benazepril x HCl via an asymmetric aza-Michael reaction.
A formal enantioselective synthesis of benazepril.HCl (4), an anti- hypertensive drug, is reported. Our synthesis employed an asymmetric aza-Michael addition of L-homophenylalanine ethyl ester (LHPE, 1) to 4-(2-nitrophenyl)-4-oxo- but-2-enoic acid methyl ester (6) as the key step to prepare (2S,3'S)-2-(2-oxo-2,3,4,5- tetrahydro-1H-benzo[b]azepin-3-ylamino)-4-phenylbutyric acid ethyl ester (8), which is the key intermediate leading to benazepril x HCl (4).
Yu
Luo-Ting
LT
Laboratory of Organometallic Chemistry, East China University of Science & Technology, Shanghai, 200237, P.R. China.
Huang
Ji-Ling
JL
Chang
Ching-Yao
CY
Yang
Teng-Kuei
TK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D012997:Solvents / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D012997:Solvents; C044946:benazepril