A series of amide derivatives of natural glycopeptide A-40,926 (A), its 6B-methyl ester (MA) and 6B-decarboxy-6B-hydroxymethyl derivative (RA) were prepared with the aim of obtaining activity against glycopeptide-resistant enterococci. These compounds are structurally related to a class of amides of 34-de(acetylglucosaminyl)-34-deoxy teicoplanin which showed interesting activity against strains of Enterococcus faecalis and E. faecium highly resistant to both vancomycin and teicoplanin. Among them, RA-amides MDL63,246 and MDL63,042 were the most active derivatives against several Gram-positive bacteria, including VanB and VanC enterococci, and were moderately active (MIC range 0.5~64/ig/ml) against strains of Enterococcus for which vancomycin and teicoplanin MICswere > 128^g/ml. The chemical rationale and the synthesis of these newseries of glycopeptide derivatives are described. Preliminary in vitro data are reported and structure-activity relationships are discussed.In the last few years an increase in serious infections caused by enterococci has been observed in hospitalized patients. Clinical isolates of enterococci are intrinsically resistant to manyclasses of antibacterial drugs, and infections often require treatment with a combination of agents to which they are moderately susceptible. The recent appearance of vancomycin-resistant enterococci poses a serious threat for the near future, particularly because high-level resistance is often associated with genetic elements which can spread from one bacterial strain to another. The emerging resistance in enterococci1} is a current challenge for glycopeptides of the dalbaheptide2) family since teicoplanin (Fig. 1),3) Amongthe teicoplanin derivatives, some basic amides (Fig. 1)4) of the 34-de(acetylglucosaminyl)-34-deoxy pseudoaglycone had interesting in vitro activity against strains of Enterococcus faecalis and E. faecium highly

No abstract

No abstract

No abstract

No abstract