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 ac id, potent and selective agonists at ionotropic glutamate receptors, have b een prepared through two different strategies. In the first approach bromon itrile oxide was added to N-BOC-Delta(3)-pyrroline or N-BOC-Delta(3)-pyrrol in-2-one and the carboxylic group was subsequently appended. The alternativ e 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 r eserved.