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

J Org Chem. 2007 Apr 13;72(8):3104-7. doi: 10.1021/jo062664i. Epub 2007 Mar 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / chemical synthesis*
  • Amidines / chemistry
  • Amino Acids / chemistry*
  • Molecular Mimicry*
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry

Substances

  • Amidines
  • Amino Acids
  • Peptides, Cyclic