Kinetic deconjugation: a gateway to the synthesis of Xxx-Gly (E)-alkene dipeptide isosteres

A new method for the preparation of Xxx-Gly (E)-alkene dipeptide isosteres (EADIs), using LDA deprotonation followed by 1 N HCl quench, was explored. The method, named kinetic deconjugation, enabled the synthesis of Tyr-Gly, Gly-Gly, Ser-Gly, Pro-Gly, and Phe-Gly EADIs, as well as one Tyr-Gly trisubstituted alkene dipeptide isostere (TADI). Overall, this method, based on commercially available materials, leads to high yields, requires few synthetic steps and works on the gram scale in the synthesis of a wide variety of EADIs.