Synthesis and Neurobiological Actions of Pyrrolidine-2,3-dicarboxylic Acids (PRDA). Conformationally Restricted Analogues of L-Aspartate.

Abstract Four stereoisomers of PRDAs 1∼4 , a novel aspartate analogue incorporating a pyrrolidine ring, were synthesized in an enantiomerically pure form starting from a chiral synthon, 5-amino-5,6-dihydropyrone. Electrophysiological experiments of 1∼4 in newborn rat spinal cords showed a variety of depolarizing activities. The conformational studies of PRDAs and their activity profile suggested that the gauche and the anti conformers about two carboxylic acid groups of Asp could be active forms to NMDA and non-NMDA receptors, respectively