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 enantionnerically pure diasteroisomers of gamma-benzyloxy-S-glutamic acid was performed using trans-4-hydroxy-L-proline as a source of chirality, while the erythro and threo isomers of D-benzyloxy-S-glutamic acid were prepared starting from (R)-Garner's 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. (C) 2009 Elsevier Ltd. All rights reserved.