Importance of the structure of vancomycin binding pocket in designing compounds active against vancomycin-resistant enterococci (VRE)

16-Membered meta,para-cyclophanes mimicking the vancomycin binding pocket (D-O-E ring) are designed and synthesized. The structural features of these biaryl ether contg. macrocycles are: (a) the deletion of the carboxyl group of vancomycin's central amino acid (amino acid D); (b) the elongation of the N-terminal; (c) the presence of lipidated aminoglucose at the D-ring. Cycloetherification by way of an intramol. nucleophilic arom. substitution reaction (SNAr) is used as a key step for the construction of the macrocycle. Min. inhibitory concns. for all of the derivs. are measured using a std. microdilution assay. Compds. 2a.apprx.2c and 3a.apprx.3c displayed weak activities against resistant strain Enterococcus faecalis L560 and were inactive against Enterococcus faecium resistant strain L2215. [on SciFinder (R)]


Published in:
Journal of Antibiotics, 59, 9, 543-552
Year:
2006
Keywords:
Note:
CAN 146:117933
10-5
Microbial, Algal, and Fungal Biochemistry
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0021-8820
written in English.
1404-90-6 (Vancomycin); 61036-62-2 (Teicoplanin) Role: BSU (Biological study, unclassified), PRP (Properties), BIOL (Biological study) (comparison; importance of the structure of vancomycin binding pocket in designing compds. active against vancomycin-resistant enterococci (VRE); 868749-94-4; 909896-38-4 Role: BSU (Biological study, unclassified), PRP (Properties), BIOL (Biological study) (importance of the structure of vancomycin binding pocket in designing compds. active against vancomycin-resistant enterococci (VRE); 918496-08-9P; 918496-33-0P; 918496-35-2P; 918496-75-0P; 918496-76-1P; 918496-77-2P Role: BSU (Biological study, unclassified), PRP (Properties), SPN (Synthetic preparation), BIOL (Biological study), PREP (Preparation) (prepn. of cyclophanes mimicking the vancomycin binding pocket; importance of the structure of vancomycin binding pocket in designing compds. active against vancomycin-resistant enterococci (VRE); 4530-20-5 (N-Boc-glycine); 16937-99-8; 24424-99-5; 26628-22-8 (Sodium azide); 74660-39-2; 918446-52-3; 918446-55-6 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of cyclophanes mimicking the vancomycin binding pocket; importance of the structure of vancomycin binding pocket in designing compds. active against vancomycin-resistant enterococci (VRE); 847505-78-6P; 918446-51-2P; 918446-53-4P; 918446-54-5P; 918446-56-7P; 918446-57-8P; 918496-13-6P; 918496-17-0P; 918496-22-7P; 918496-24-9P; 918496-26-1P; 918496-29-4P; 918496-31-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of cyclophanes mimicking the vancomycin binding pocket; importance of the structure of vancomycin binding pocket in designing compds. active against vancomycin-resistant enterococci (VRE)
Laboratories:




 Record created 2010-11-25, last modified 2018-09-13


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