An unexpected intramolecular cyclization of isothiouronium teicoplanins. II. Reaction mechanism and biological activity.
N15-Isothiouronium derivatives of teicoplanin and its aglycone submitted to alkaline condition give rise to an intramolecular cyclization. The structures of the new gamma-lactam derivatives were determined by using 1H NMR, IR and fast atom bombardment mass spectra. The cyclization mechanism was interpreted on the basis of the identification of the intermediate structure. The poor in vitro antibacterial activity of the new cyclic compounds and the negligible affinity for the synthetic peptidoglycan model Ac2-L-Lys-D-Ala-D-Ala is probably due to the lack of the N-17 amidic proton and to the lack of the basic character of the nitrogen in position 15.
Trani
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A
Lepetit Research Center, Gerenzano (VA), Italy.
Ferrari
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P
Pallanza
R
R
Ciabatti
R
R
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D003500:Cyclization; D006020:Glycopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis*; D007550:Isothiuronium / Q000031:analogs & derivatives*; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013057:Spectrum Analysis; D017334:Teicoplanin; D013890:Thiourea / Q000031:analogs & derivatives*
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D006146:Guanidines; D007769:Lactams; D007550:Isothiuronium; D017334:Teicoplanin; D013890:Thiourea