Azirine-containing dipeptides and depsipeptides: synthesis, transformations and antibacterial activity

Azirine-containing dipeptides and depsipeptides with a wide range of substituents have been synthesized in high yields via the Passerini and Ugi multicomponent reactions (MCRs) using 2 H -azirine-2-carboxylic acids as the acid component. The obtained MCR adducts have been transformed to lactam-fused aziridines, as well as pyrrole, imidazole, aziridine, and other derivatives, containing the dipeptide or depsipeptide moiety. The azirine-containing depsipeptides exhibit antibacterial activity against the ESKAPE pathogens, especially Gram-positive bacterial strains ( E. faecium - MIC 16 μg mL −1 , S. aureus - MIC 9 μg mL −1 ). The Passerini and Ugi reactions with 2 H -azirine-2-carboxylic acids gave novel antibacterial active 2 H -azirines containing the dipeptide or depsipeptide moiety, which can be transformed to fused aziridines.