Use of a modified ring-switching strategy to synthesise the glutamate antagonist (2S)-2-amino-3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)propionate and related compounds with two chiral centres1
DinsmorePresent address: Department of Chemistry, University of Witwatersrand, PO WITS 2050, South Africa., Andrew; DoylePresent address: BioFocus plc, 130 Abbott Drive, Sittingbourne Research Centre, Sittingbourne, Kent, UK ME9 8AZ., Paul M.; Young, Douglas W.; DinsmorePresent address: Department of Chemistry, University of Witwatersrand, PO WITS 2050, South Africa. Andrew; Sussex Centre for Biomolecular Design and Drug Development, University of Sussex; DoylePresent address: BioFocus plc, 130 Abbott Drive, Sittingbourne Research Centre, Sittingbourne, Kent, UK ME9 8AZ. Paul M.; Sussex Centre for Biomolecular Design and Drug Development, University of Sussex; Young Douglas W.; Sussex Centre for Biomolecular Design and Drug Development, University of Sussex
Журнал:
Journal of the Chemical Society, Perkin Transactions 1
Дата:
2001
Аннотация:
(2S)-2-Amino-3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)propionic acid 8, an isomer of the natural product willardiine 7, was synthesised by treatment of the pyroglutamate urea 19 with mild base followed by deprotection in a two-step modification of our â ring-switchingâ approach to the synthesis of glutamate antagonists. Use of this two-step strategy has allowed us to synthesise l-alanine derivatives, which are β-substituted by a reduced pyrimidinedione which contains a second chiral centre. In one case, the antagonist activity at metabotropic glutamate receptors of two diastereoisomers showed little difference.
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