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)]