Advances in the kinetic and dynamic kinetic resolution of piperazine-2-carboxylic acid derivatives with Candida Antarctica lipase A; Structural requirements for enantioselective N-acylation

Abstract

The kinetic resolution of piperazine-2-carboxylic acid was studied as its N-4- and N-1-Bocpiperazine-2-carboxylic acid methyl esters, rac-1 and -2, respectively. Lipase A from Candida antarctica (CAL-A) catalyzed highly enantioselective (e>200 for rac-1 and 200 for rac-2) Nacylation of both compounds with 2,2,2-trifluoroethyl butanoate in TBME. Aldehyde-based dynamic kinetic resolution of rac-1 with vinyl butanoate in acetonitrile gave up to 75% product yield with S-absolute configuration in 48 hours. The present results together with literature data suggest that CAL-A -catalyzed N-acylation is enhanced in terms of reaction rate or enantioselectivity when an electron rich structure, such as carboxylic ester or aromatic ring, is attached to the asymmetric center next to the secondary ring nitrogen. © ARKAT-USA, Inc.