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Synthesis of amino acid-derived cyclic acyl amidines for use in beta-strand peptidomimetics.

ABSTRACT: The acyl amidine represented by the 4,5-dihydro-2(3H)-pyrazinone ring system 2 is isosteric to the vinylogous amide of the 1,2-dihydro-3(6H)-pyridinone 1, but its assembly from separate amine and amide components enables ready incorporation of an amino acid side chain with correct regio- and stereochemistry. beta-Strand peptidomimetics incorporating amino acid analogues based on 2 have recently been shown to be potent, protease-resistant ligands to a PDZ protein-interaction domain. Two routes to the protected dipeptide analogue 3 are described.

SUBMITTER: Hammond MC

PROVIDER: S-EPMC2536638 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Synthesis of amino acid-derived cyclic acyl amidines for use in beta-strand peptidomimetics.

Hammond Ming C MC Bartlett Paul A PA

The Journal of organic chemistry 20070320 8

The acyl amidine represented by the 4,5-dihydro-2(3H)-pyrazinone ring system 2 is isosteric to the vinylogous amide of the 1,2-dihydro-3(6H)-pyridinone 1, but its assembly from separate amine and amide components enables ready incorporation of an amino acid side chain with correct regio- and stereochemistry. beta-Strand peptidomimetics incorporating amino acid analogues based on 2 have recently been shown to be potent, protease-resistant ligands to a PDZ protein-interaction domain. Two routes to ...[more]

PMID: 17371075

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