Syntheses of optically pure beta-hydroxyaspartate derivatives as glutamatetransporter blockers

DL-threo-beta -Benzyloxyaspartate (DL-TBOA) is a non-transportable blocker of the glutamate transporters that serves as an indispensable tool for the investigation of the physiological roles of the transporters. To examine th e precise interaction between a blocker and the transporters, we synthesize d the optically pure isomers (L- and D-TBOA) and its erythro-isomers. L-TBO A is the most potent blocker for the human excitatory amino acid transporte rs (EAATI-3), while D-TBOA revealed a difference in the pharmacophores betw een EAAT1 and EAAT3. We also synthesized the substituent Variants (methyl o r naphthylmethyl derivatives) of L-TBOA, The results obtained here suggest that bulky substituents are crucial for non-transportable blockers. (C) 200 0 Elsevier Science Ltd. All rights reserved.