AMIDES OF DE-ACETYLGLUCOSAMINYL-DEOXY TEICOPLANIN ACTIVE AGAINST HIGHLY GLYCOPEPTIDE-RESISTANT ENTEROCOCCI - SYNTHESIS AND ANTIBACTERIAL ACTIVITY

Removal, by selective reduction, of the acetylglucosamine from teicopl anin A2-2 (CTA/2) produced the 34-de(acetylglucosaminyl)-34-deoxy pseu doaglycone (II). This compound was more active in vitro than CTA/2 aga inst coagulase-negative staphylococci (CNS). Amide derivatives obtaine d by condensation of the carboxyl group of II with primary amines were particularly active against Streptococcus pyogenes and had some in vi tro activity against VanA enterococci highly resistant to both teicopl anin and vancomycin. Among them, a carboxamide (VII) with a branched t etramine also had better activity than the corresponding amide of teic oplanin against CNS. In contrast, the dimethylamide (VIII) of II had l ittle activity against VanA enterococci. While the overall structure o f the heptapeptide backbone of the secondary carboxamides of II is the same as in CTA/2 and its amide derivatives, in deoxy pseudoaglycone I I and its tertiary amide VIII the 51,52-peptide bond undergoes a confo rmational change from the original cisoid to the transoid orientation. This difference between the secondary amides of II and dimethylamide VIII is reflected in their different antibacterial spectrum. The direc t synthesis of the amides of deoxy pseudoaglycone II from parent CTA/2 -amides by reaction with sodium borohydride is also described.