Synthesis of carbamate-type caged derivatives of a novel glutamate transporter blocker.
L-threo-beta-Benzyloxyaspartate (L-TBOA) and (2S,3S)-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.
Takaoka
Kiyo
K
Suntory Institute for Bioorganic Research, Shimamoto, Osaka, Japan.
Tatsu
Yoshiro
Y
Yumoto
Noboru
N
Nakajima
Terumi
T
Shimamoto
Keiko
K
D000586:Amination; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D005461:Fluorine / Q000737:chemistry*; D018698:Glutamic Acid / Q000378:metabolism; D008745:Methylation; D015394:Molecular Structure; D013057:Spectrum Analysis
D027322:Amino Acid Transport System X-AG; D002219:Carbamates; C120673:benzyloxyaspartate; D005461:Fluorine; D001224:Aspartic Acid; D018698:Glutamic Acid