SYNTHESIS OF L-2-(2-CARBOXY-4-METHYLENECYCLOPENTYL)GLYCINES (CPGS) - NOVEL CONFORMATIONALLY RESTRICTED GLUTAMATE ANALOGS

Three diastereomers 1, 2, and 4 of a new glutamate analogue incorporating a 5-membered ring were synthesized in a stereocontrolled manner. 1'R-Isomers 2 and 4 were constructed from the alpha,beta-unsaturated 2,2,2-trifluoroethyl esters 5b and 10b by a [3+2] cycloaddition with a Pd-trimethylenemethane (TMM) complex. The 1'S isomer 1 was synthesized by a 1,4-addition of TMM equivalent to the alpha,beta-unsaturated methyl ester 10a. The folded isomer 4 was characterized electrophysiologically to be a potent agonist of kainate receptors in the mammalian central nervous systems.