Extension of ring switching strategy to the glutamate antagonist 2-(pyrimidin-2,4-dione-5-ylmethyl)-(2S)-glycine and related compounds with two chiral centres

2-(Pyrimidin-2,4-dione-5-ylmethyl)-(2S)-glycine 8 has been prepared by treatment of the pyroglutamate urea 12 with mild base, followed by deprotection in a modification of our ring switching approach to the synthesis of glutamate antagonists. The product is an isomer of the natural product willardiine 7. Use of this two step strategy has allowed us to synthesise l-alanine derivatives, which are β-substituted by a reduced pyrimidinedione containing a second chiral centre. There is little difference between the diastereoisomers of one of these compounds as antagonists at metabotropic glutamate receptors.