Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action

Laspartomycin C is a lipopeptide antibiotic with activity against a range of Gram-positive bacteria including drug resistant pathogens. We report the first total synthesis of laspartomycin C as well as a series of structural variants. Laspartomycin C was found to specifically bind undecaprenyl phosphate (C-55-P) and inhibit formation of the bacterial cell wall precursor lipid II. While several clinically used antibiotics target the lipid II pathway, there are no approved drugs that act on its C-55-P precursor.