Malabarba A, Ciabatti R, Scotti R, Goldstein B P, Ferrari P, Kurz M, Andreini B P, Denaro M
Marion Merrell Dow Research Institute, Lepetit Research Center, Gerenzano (Varese), Italy.
J Antibiot (Tokyo). 1995 Aug;48(8):869-83. doi: 10.7164/antibiotics.48.869.
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 MDL 63,246 and MDL 63,042 were the most active derivatives against several Gram-positive bacteria, including VanB and VanC enterococci, and were moderately active (MIC range 0.5 approximately 64 micrograms/ml) against strains of Enterococcus for which vancomycin and teicoplanin MICs were > or = 128 micrograms/ml. The chemical rationale and the synthesis of these new series of glycopeptide derivatives are described. Preliminary in vitro data are reported and structure-activity relationships are discussed.
制备了一系列天然糖肽A - 40,926（A）、其6B - 甲酯（MA）和6B - 脱羧 - 6B - 羟甲基衍生物（RA）的酰胺衍生物，目的是获得抗糖肽耐药肠球菌的活性。这些化合物在结构上与一类34 - 去（乙酰葡糖胺基）- 34 - 脱氧替考拉宁的酰胺相关，后者对粪肠球菌和屎肠球菌的万古霉素和替考拉宁高度耐药菌株显示出有趣的活性。其中，RA - 酰胺MDL 63,246和MDL 63,042是对几种革兰氏阳性菌（包括VanB和VanC肠球菌）活性最强的衍生物，对万古霉素和替考拉宁MIC≥128微克/毫升的肠球菌菌株有中度活性（MIC范围为0.5至约64微克/毫升）。描述了这些新系列糖肽衍生物的化学原理和合成方法。报告了初步的体外数据并讨论了构效关系。
