A new series of glycopeptide antibiotics incorporating a squaric acid moiety. Synthesis, structural and antibacterial studies.
The aglycones of the antibiotics eremomycin, vancomycin and ristocetin (3, 4 and 6, respectively) were prepared by deglycosidation of the parent antibiotics with hydrogen fluoride, and complete assignation of their 1H, 13C and 15N spectra was performed. The squaric acid amide esters (11-14), were prepared from dimethyl squarate. The corresponding asymmetric diamides (16-19, 22, 23) were also synthesized using 4-phenylbenzylamine and triglycine. The advantage of the method is the high regioselectivity and that no protecting group strategy is required. Electrospray mass spectroscopic method was elaborated for the determination of the site of substitution of the modified antibiotics. The antibacterial activity of the prepared compounds is discussed in detail.
Sztaricskai
Ferenc
F
Research Group for Antibiotics of the Hungarian Academy of Sciences, and Department of Pharmaceutical Chemistry, University of Debrecen, H-4010 Debrecen, PO.Box 70, Hungary. sztarife@delfin.unideb.hu
Batta
Gyula
G
Herczegh
Pál
P
Balázs
Attila
A
Jeko
József
J
Roth
Erzsébet
E
Szabó
Pál T
PT
Kardos
Szilvia
S
Rozgonyi
Ferenc
F
Boda
Zoltán
Z
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012310:Ristocetin / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014640:Vancomycin / Q000737:chemistry
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C053759:eremomycin; D012310:Ristocetin; D014640:Vancomycin