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

Kleijn, Laurens
H. J.; Oppedijk, Sabine F.; Hart, Peter ’t; M. van Harten, Roel; Martin-Visscher, Leah A.; Kemmink, Johan; Breukink, Eefjan; Martin, Nathaniel I.

doi:10.1021/acs.jmedchem.6b00219.s001

jm6b00219_si_001.pdf (20.93 MB)

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

journal contribution

posted on 2016-03-11, 00:00 authored by Laurens H. J. Kleijn, Sabine F. Oppedijk, Peter ’t Hart, Roel M. van Harten, Leah A. Martin-Visscher, Johan Kemmink, Eefjan Breukink, Nathaniel I. Martin

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 (C₅₅-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 C₅₅-P precursor.