Design and Synthesis of Chloroalkene Dipeptide Isosteres as Ground State Peptidomimetics for drug discovery

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As part of a program aimed at acceleration of the peptide-lead drug discovery, synthetic studies and a structural analysis of a newly designed dipeptide bioisosteres possessing an E/Z-chloroalkene unit as the surrogate functionality of a peptide bond were investigated. In this study, practical and divergent methodologies for the synthesis of chloroalkenes dipeptide isosteres (CADIs) have been developed including large-scale synthesis of Xaa-Gly-type CADIs and highly diastereoselective synthesis of Xaa-Xaa-type CADIs. These studies should contribute to the development of alkene dipeptide isosteres-based medicinal chemistry.