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 trea tment of the pyroglutamate urea 12 with mild base, followed by deprotection in a modification of our ring switching approach to the synthesis of gluta mate antagonists. The product is an isomer of the natural product willardii ne 7. Use of this two step strategy has allowed us to synthesise L-alanine derivatives, which are beta -substituted by a reduced pyrimidinedione conta ining a second chiral centre. There is little difference between the diaste reoisomers of one of these compounds as antagonists at metabotropic glutama te receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.