Synthesis of carbamate-type caged derivatives of a novel glutamate transporter blocker

Carbamate-type caged blockers for glutamate transporters, N-BCMCMC-TBOA and N-BCMCMC-TFB-TBOA, were synthesized and revealed to be stable in aqueous solution. Photolysis of N-BCMCMC-TBOAs immediately released l-TBOAs to inhibit glutamate uptake. l- threo-β-Benzyloxyaspartate ( l-TBOA) and (2 S,3 S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy}aspartate ( l-TFB-TBOA) are potent nontransportable blockers for glutamate transporters. We synthesized a carbamate-type coumarin derivative of l-TBOA 3a as a caged blocker and compared 3a with the corresponding ester-type analogs 1. The carbamate 3a was less sensitive to photolysis than the ester 1 but was more stable in the aqueous solution. The [6,7-bis(carboxymethoxy)-coumarin-4-yl]methylcarbonyl (BCMCMC) group exhibited good results both in photoreactivity and stability. Therefore, we examined photolysis of N-BCMCMC-TBOA 3b and N-BCMCMC-TFB-TBOA 4, which immediately released blockers to show glutamate uptake inhibition.