Synthesis and structure-activity relationship studies of teixobactin analogues

A new series of teixobactin analogues were synthesized via an oxidative cyclative cleavage approach using aryl hydrazide resin as the solid support. Structure-activity relationship studies revealed that the guanidine or amine group at position 10, the hydroxyl group of Ser(7) residue and the NH proton of the N-terminal Phe(1) residue are critical to the antibacterial activities, while side chain size and functional group changes are tolerated at position 4. These findings will facilitate the development of new teixobactin analogues with enhanced pharmacological properties.