对万古霉素耐药肠球菌有活性的糖肽羧酰胺

Glycopeptide carboxamides active against vancomycin-resistant enterococci.

作者信息

Zweifel Mark J, Snyder Nancy J, Cooper Robin D G, Nicas Thalia I, Mullen Deborah L, Butler Thomas F, Rodriguez Michael J

机构信息

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

出版信息

J Antibiot (Tokyo). 2003 Mar;56(3):289-95. doi: 10.7164/antibiotics.56.289.

DOI:10.7164/antibiotics.56.289

PMID:12760685

Abstract

Glycopeptide antibiotics were synthesized via the PyBOP mediated condensation of aliphatic, heterocyclic and aromatic amines with the C-terminus of vancomycin, LY264826 (A82846B) and semi-synthetic derivatives of these natural products. Amides of LY264826 and vancomycin demonstrated excellent activity against staphylococci and streptococci as compared to the parent natural product. However, the amides of N-alkylated LY264826 and N-alkylated vancomycin were active against vancomycin-resistant enterococci as well as other gram-positive pathogens such as Staphylococcus aureus, S. haemolyticus, S. epidermidis and Streptococcus pneumoniae.

摘要

糖肽类抗生素是通过PyBOP介导的脂肪族、杂环和芳香胺与万古霉素C端、LY264826（A82846B）以及这些天然产物的半合成衍生物缩合而成。与母体天然产物相比，LY264826和万古霉素的酰胺对葡萄球菌和链球菌表现出优异的活性。然而，N-烷基化LY264826和N-烷基化万古霉素的酰胺对万古霉素耐药肠球菌以及其他革兰氏阳性病原体如金黄色葡萄球菌、溶血葡萄球菌、表皮葡萄球菌和肺炎链球菌具有活性。