Abstract
Literature publications (up to September 2006) concerning the synthesis of ω-phosphinyl-α-amino acids and their development towards use as therapeutic agents are reviewed. General and asymmetric methodologies for the preparation of straight-chain examples are described, including AP3-7 modulators of glutamate-responsive excitatory amino acid (EAA) receptors (i.e. ionotropic NMDA-, and metabotropic GrpIII mGlu-receptors), and the glutamate synthetase inhibitor phosphinothricin. Focusing primarily on the development of methods for introducing phosphonate and aminocarboxylate functions to the appropriate scaffold, approaches to conformationally constrained ω-phosphinyl-α-amino acids are also investigated, along with their relevance to the development of therapeutic regimens towards neurodegenerative disorders.
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