Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide

Abstract

A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth.