Synthetic Studies on Amide Bond Isosteres and Their Application to Artificial CXCR4 Ligands

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Replacement of the planar amide bond with a surrogate alkene substructure represents a promising approach to overcome their major limitations such as poor bioavailability and short physiological half-life, which limit their medicinal and biological use. However, development of effective ground state isosteric and isoelectronic analogues of the amide bond have yet to be developed. In this study, synthetic methodologies for a newly designed chloroalkene dipeptide isosteres (CADIs) were examined to develop diastereoselective, divergent, and practical synthetic approaches toward (Z)-chlororalkene and (E)-chloroalklene isostere skeletons utilizing organocopper-mediated reactions. These studies should contribute to the development of peptidomimetics-based medicinal chemistry.