Synthesis and biological evaluation of de(acetylglucosaminyl)didehydrodeoxy derivatives of teicoplanin antibodies.
A series of 34-de(acetylglucosaminyl)-34-deoxy derivatives of 34,35- and 35,52-didehydro teicoplanin antibiotics have been synthesized from teicoplanin and its N-acetylglucosamine containing pseudoaglycons under basic conditions. The structures of these compounds have been determined by 1H NMR, UV, and FAB-MS. 35,52-Unsaturated derivatives maintained in vitro and in vivo antimicrobial activity to a different extent as well as the ability for binding to Ac2-L-Lys-D-Ala-D-Ala, a bacterial cell-wall model for the site of action of glycopeptide antibiotics. In contrast, 34,35-unsaturated compounds were markedly less active and possessed a negligible affinity for the synthetic tripeptide.
Malabarba
A
A
Merrell Dow Research Institute, Lepetit Research Center, Gerenzano (Varese), Italy.
Trani
A
A
Tarzia
G
G
Ferrari
P
P
Pallanza
R
R
Berti
M
M
D000117:Acetylglucosamine; D000818:Animals; D000900:Anti-Bacterial Agents; D001419:Bacteria / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D004755:Enterobacteriaceae / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives; D006020:Glycopeptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013210:Staphylococcus / Q000187:drug effects; D013290:Streptococcal Infections / Q000188:drug therapy; D013291:Streptococcus / Q000187:drug effects; D017334:Teicoplanin
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D009842:Oligopeptides; D010457:Peptidoglycan; D017334:Teicoplanin; D005944:Glucosamine; D000117:Acetylglucosamine