ENANTIOSELECTIVE SYNTHESIS OF AMINO-3-(3-HYDROXY-5-METHYLISOXAZOL-4-YL)PROPANOIC ACID (S)-AMPA

(S)-AMPA (11) is an isoxazole containing alpha-amino acid used for sel ectively labeling the homonymous excitatory amino acid (EAA) receptor. Until now only enzymatic methods have been devised for its preparatio n. An asymmetric synthesis of (S)-AMPA is reported which exploits the formation of 3-bromo-4-hydroxymethyl-5-methylisoxazole intermediate 3 in a potassium fluoride promoted 1,3-dipolar cycloaddition and the app lication of the bislactim ether methodology for introducing the chiral alpha-amino acid center.