Synthesis of amino acid-derived cyclic acyl amidines for use in beta-strand peptidomimetics.
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.
Hammond
Ming C
MC
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.
Bartlett
Paul A
PA
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D018716:Molecular Mimicry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry
D000578:Amidines; D000596:Amino Acids; D010456:Peptides, Cyclic