Synthesis of new β- and γ-benzyloxy-S-glutamic acid derivatives and evaluation of their activity as inhibitors of excitatory amino acid transporters

An efficient stereoselective preparation of the two enantiomerically pure diasteroisomers of γ-benzyloxy-S-glutamic acid was performed using trans-4-hydroxy-l-proline as a source of chirality, while the erythro and threo isomers of β-benzyloxy-S-glutamic acid were prepared starting from (R)-Garnerʹs aldehyde. All new derivatives were tested for their inhibitory activity against excitatory amino acid transporters in a rat synaptosomal preparation and their IC50 values were compared to that of TBOA, a one carbon lower homologue commonly used as the reference blocker of glutamate transporters.