Syntheses of optically pure β-hydroxyaspartate derivatives as glutamate transporter blockers

-threo-β-Benzyloxyaspartate ( -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 the precise interaction between a blocker and the transporters, we synthesized the optically pure isomers ( - and -TBOA) and its erythro-isomers. -TBOA is the most potent blocker for the human excitatory amino acid transporters (EAAT1–3), while -TBOA revealed a difference in the pharmacophores between EAAT1 and EAAT3. We also synthesized the substituent variants (methyl or naphthylmethyl derivatives) of -TBOA. The results obtained here suggest that bulky substituents are crucial for non-transportable blockers