Chemistry of glutamate analogues

Abstract

Stereoselective syntheses of four diastereoisomers of ß-benzylglutamic acid were performed through Michael addition of benzylphenylsulfide to the lactone and the lactam which were prepared from serine and glutamic acid respectively. (2S,3R)-ß-Benzylglutamic acid whose configuration was the same as that of kainic acid exhibited threefold neuroexcitatory activity in the isolated rat spinal cord than glutamate and other isomers showed very little activity. A new synthetic method of acromelic acid families was also developed. The enolate of an aromatic aldehyde and a vinyl group, both of which were linked with amino nitrogen, underwent intramolecular Diels-Alder addition reaction with excellent stereoselectivity to give the proline derivative with desired configuration. From this product, a methoxyphenyl kainoid (3-carboxy-methylproline with methoxyphenyl group at C4) with the same configuration in pyrrolidine ring as kainic acid was derived. The methoxyphenyl kainoid showed potent activity comparable to that of acromelic acid B or domoic acid.