title: Enantioselective biotransformations of racemic and meso pyrrolidine-2,5-dicarboxamides and their application in organic synthesis.
abstract: In this paper, we report the amidase-catalyzed hydrolysis of pyrrolidine-2,5-dicarboxamides and their application in organic synthesis. Catalyzed by Rhodococcus erythropolis AJ270, an amidase containing microbial whole cell catalyst, racemic trans-pyrrolidine-2,5-carboxamide was kinetically resolved into (2S,5S)-pyrrolidine-2,5-dicarboxamide and (2R,5R)-5-carbamoylpyrrolidine-2-carboxylic acid in high yields and excellent enantioselectivity. Biocatalytic desymmetrization of meso cis-pyrrolidinedicarboxamide afforded enantiomerically pure (2R,5S)-5-carbamoylpyrrolidine-2-carboxylic acid in an almost quantitative yield. In both kinetic resolution and desymmetrization, the amidase always exhibited excellent 2R-enantioselectivity, although its catalytic efficiency was influenced dramatically by the steric effect of the substituent on the nitrogen atom of pyrrolidine ring. The synthetic potential of biotransformation was demonstrated by the scalable preparation of (2R,5R)- and (2R,5S)-5-carbamoylpyrrolidine-2-carboxylic acids and their conversions to aza-nucleoside analogues and druglike pyrroline-fused diazepin-11(5H)-one compounds.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: De-Xian
authors.initials: DX
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Wang
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D007700:Kinetics; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C573967:(2R,5R)-5-carbamoylpyrrolidine-2-carboxylic acid; D002264:Carboxylic Acids; D011759:Pyrrolidines; C032519:pyrrolidine