Synthesis and evaluation of ether and halogenated derivatives of mannopeptimycin glycopeptide antibiotics

A number of 6- O-ether and 4- O-ether derivatives of mannopeptimycin-α with different steric bulk and lipophilicity were synthesized for structure–activity relationship study. Novel iodo and bromo mannopeptimycin-α were also prepared. These compounds were synthesized via electrophilic aromatic substitution. Many of the new ether derivatives exhibited potent antibacterial activity against Gram-positive resistant strains including VRE, MRSA, and PRSP. A number of novel 6- O and 4- O-ether derivatives of mannopeptimycin glycopeptide and halogenated derivatives (X=I, Br) were synthesized for SAR. Many of the more lipophilic ether derivatives showed potent in vitro antibacterial activity against VRE, MRSA, and PRSP.