(E)-Alkene Peptide Bond Isosteres by Cuprate Opening of Vinyl Aziridines

Alkene isosteres are important nonhydrolyzable and rigidified analogs of peptide bonds. The ( E -alkene effectively mimics the three-dimensional structure of the amide bond, especially the C(α) n −C(α) n+1 distance (Fig. 1 ). The incorporation of an alkene isostere into a biologically active peptide provides a peptidomimetic that should have improved resistance to proteolysis and similar conformational preferences. The low polarity of the alkene is useful in increasing lipophilicity, but hydrogen bonding or dipolar interactions are generally not possible.   Fig. 1.  Geometry of peptide bond and alkene isostere.