Isoxazole amino-acids as glutamic acid agonists. Synthesis of some analogues and homologues of ibotenic acid

Abstract

(R,S)-α-Amino-3-hydroxy-4-methylisoxazol-5-ylacetic acid (4-methylibotenic acid)(14) was prepared via amination of 3-methoxy-4-methylisoxazol-5-ylacetic acid (12) with O-mesitylenesulphonyloxyamine. (R,S)-α-Amino-3-hydroxyisoxazol-5-ylpropionic acid (homoibotenic acid)(17), (R,S)-α-amino-4-bromo-3-hydroxyisoxazol-5-ylpropionic acid (4-bromohomoibotenic acid) monohydrate (24), and (R,S)-α-amino-3-hydroxy-5-methylisoxazol-4-ylpropionic acid monohydrate (33) were all synthesized via alkylation of diethyl acetamidomalonate. An alternative synthesis of homoibotenic acid proceeded by addition of ammonia to (E)-3-methoxyisoxazol-5-ylpropenoic acid (16) with concurrent tin(IV)-induced cleavage of the methoxy-group. This ether cleavage under basic conditions appears to be of general utility for the deprotection of 3-methoxyisoxazoles.