The CuI-catalyzed alkyne-azide cycloaddition as direct conjugation/cyclization method of peptides to steroids

The CuI-catalyzed azide-alkyne 1,3-dipolar cycloaddition is implemented as a direct conjugation method of alkynyl peptides to azidosteroids, enabling the preparation of novel triazole-linked peptide-steroid conjugates in good to excellent yields. The process comprised the solution-phase synthesis of oligopeptides featuring varied chain length and amino acid sequence as well as the preparation of a small library of azidosteroids bearing the azido group either at the side chain or the steroidal nucleus. An alternative strategy relying on a sequential peptide coupling/CuAAC-based macrocyclization procedure was also developed to afford macrocyclic peptide-steroid conjugates featuring different sizes and topologies. Both methods showed great chemical efficiency and versatility, thus showing promise toward the future preparation of conjugates with potential pharmaceutical and biological applications.