A bidirectional access to novel thiadiazine hybrid molecules by double multicomponent reactions

Abstract In an attempt to further exploit multicomponent reactions in the field of hybrid heterocyclic molecules, we describe a bidirectional approach for the synthesis of novel 1,3,5-thiadiazine-peptides molecules. The process relies on the execution of two Ugi reactions between dicarboxy-functionalized 1,3,5-thiadiazine with different amines and isocyanides. An alternative strategy relying on a sequential multicomponent macrocyclization procedure was also developed to afford thiadiazine peptide-like macrocycles. Both methods showed great chemical efficiency and versatility.