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-alpha with different steric bulk and lipophilicity were synthesized for structure-activity relationship study. Novel iodo and bromo mannopeptimycin-alpha 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.
Sum
Phaik-Eng
PE
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. sump@wyeth.com
How
David
D
Torres
Nancy
N
Petersen
Peter J
PJ
Ashcroft
Joseph
J
Graziani
Edmund I
EI
Koehn
Frank E
FE
Mansour
Tarek S
TS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004986:Ether / Q000737:chemistry; D006020:Glycopeptides; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006219:Halogens / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D006219:Halogens; C478082:mannopeptimycin; D004986:Ether