Identification of synthetic compounds active against VRE: the role of the lipidated aminoglucose and the structure of glycopeptide binding pocket

Synthesis of modified vancomycin binding pocket (D-O-E ring) incorporating a (R)- or (S)-configured secondary alcohol function at the AA4 position is described. The presence of both the lipidated aminoglucose (part A) and the structure of the 16-membered macrocycle (part B) are important for the observed activities of the modified vancomycin D-O-E ring against VRE. The polyamine appendage at the C-terminal (part C), on the other hand, improved the activity against vancomycin-sensitive strains.