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
A. Dinsmore et al., 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, TETRAHEDR L, 41(51), 2000, pp. 10153-10158
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.