Synthesis of new bicyclic analogues of glutamic acid

Regioisomeric 3-hydroxyisoxazolinyl prolines {[HIP-A (+/-)-6 and HIP-B (+/-)-7], which represent a restricted conformation of NMDA, AMPA, and kainic acid, potent and selective agonists at ionotropic glutamate receptors, have been prepared through two different strategies. In the first approach bromonitrile oxide was added to N-BOC-Delta(3)-pyrroline or N-BOC-Delta(3)-pyrrolin-2-one and the carboxylic group was subsequently appended. The alternative strategy is based on the cycloaddition of the same 1,3-dipole to NBOC-3,3-didehydroproline methyl ester, (C) 1999 Elsevier Science Ltd. All rights reserved.}