An easy two step synthesis of macrocyclic peptidotriazoles via a four-component reaction and copper catalyzed intramolecular azide–alkyne [3+2] click cycloaddition

A two-step macrocyclization strategy for the synthesis of 12- and 14-membered cyclic peptidotriazoles by combining a one pot four-component reaction and an intramolecular 3+2] azide–alkyne click cycloaddition reaction is described. Macrocycles are obtained in good to excellent yield from the aqueous work-up of the reaction mixture and it is possible to expand or contract the ring size by adjusting the length of the nitrile moiety used in the MCR stage.