Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers.
The beta-amino acid, (S)-ethyl-3-amino-4-pentynoate, is a chiral synthon used in the synthesis of xemilofiban hydrochloride, an anti-platelet agent. A biocatalytic approach was developed to resolve (R)- and (S)-enantiomers of ethyl 3-amino-4-pentynoate in enantiomerically pure form employing the enzyme Penicillin acylase. In the acylation, phenylacetic acid was used as an acylating agent. We have shown that both the acylation and deacylation can be employed and that the activity of the enzyme Penicillin acylase can be controlled by maintaining an appropriate pH of the reaction medium.
Topgi
R S
RS
R&D, Chemical Sciences, SEARLE, Skokie, IL 60077, USA.
Ng
J S
JS
Landis
B
B
Wang
P
P
Behling
J R
JR
D000215:Acylation; D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001550:Benzamidines / Q000138:chemical synthesis; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000201:enzymology; D006868:Hydrolysis; D007536:Isomerism; D010399:Penicillin Amidase / Q000737:chemistry* / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis; D013379:Substrate Specificity
D000577:Amides; D000596:Amino Acids; D001550:Benzamidines; D010975:Platelet Aggregation Inhibitors; C401947:ethyl 3-amino-4-pentynoate; D010399:Penicillin Amidase; C091295:xemilofiban