Macrocyclic Pseudopeptides Having Proline or Pipecolic Acid Residues. Efficient Synthesis via Ugi-Click Strategy

Efficient synthesis of 12-28 membered 1,2,3-triazole containing macrocyclic peptidomimetics having proline or pipecolic acid residue in the structure was elaborated using Ugi-Click-strategy. The corresponding linear peptidomimetics prepared via Ugi reaction were isolated in up to 86 % yield. Ring closure by CuAAC was investigated to reveal the influence of the structure of Ugi products on the course of the click-macrocyclization. Possibility of the synthesis either monomeric (12- and 13-membered) or dimeric (24-, 26- and 28-membered) macrocycles in up to 98 % yield by proposed approach was demonstrated.