First chemoenzymatic synthesis of (+)‐2‐carboxypyrrolidine‐3‐acetic acid, the nucleus of kainoid amino acids

The distinctive nucleus of kainoid amino acids, (2 S ,3 R )‐(+)‐2‐carboxypyrrolidine‐3‐acetic acid 6 , was synthesized by a chemoenzymatic process, exploiting the diastereomeric cis / trans methyl pyroglutamate derivatives 10a , 10b , 10c / 11a , 11b , 11c as key intermediates. These mixtures, when subjected to a kinetic resolution mediated by α‐chymotrypsin, reacted diastereo‐, regio‐, and enantioselectively to give the trans derivatives (+)‐ 10a , 10b , 10c possessing the correct (2 S ,3 R ) configuration. Subsequently, the desired product (2 S ,3 R )‐(+)‐ 6 could be obtained after well‐established transformations. Chirality, 2012. © 2011 Wiley Periodicals, Inc.