ABSTRACT
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).
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemical synthesis , Benzazepines/chemical synthesis , Models, Chemical , Angiotensin-Converting Enzyme Inhibitors/chemistry , Benzazepines/chemistry , Solvents/chemistryABSTRACT
Biosynthesis of (S)-(+)-2-amino-4-phenylbutanoic acid (1) was performed by nonenantioselective hydantoinase and L-N-carbamoylase using racemic 5-[2-phenylethyl]-imidazolidine-2,4-dione (rac-2) as a substrate. The compounds involved in this biocatalysis process could be simultaneously resolved by high-performance liquid chromatography using Chirobiotic T column with a mobile phase of EtOH/H(2)O = 10/90 at pH 4.2-4.5. To our knowledge, this is the first report of the successful production of 1 by the combination of recombinant hydantoinase and L-N-carbamoylase.
Subject(s)
Amidohydrolases/chemistry , Aminobutyrates/chemical synthesis , Bacillus/enzymology , Catalysis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , StereoisomerismABSTRACT
Optically active new pyridyl alcohols 1-4, which can be easily synthesized by the reaction of (+)-camphor or (-)-menthone with lithiated pyridine derivatives, were applied as chiral ligands in the asymmetric addition of diethylzinc to aldehydes. Good yields with up to 94.0% enantiomeric excesses were observed in these reactions.
