Installation of an aryl boronic acid function into the external section of -aryl-oxazolidinones: Synthesis and antimicrobial evaluation

N-aryl-oxazolidinones is a prominent family of antimicrobials used for treating infections caused by clinically prevalent Gram-positive bacteria. Recently, boron-containing compounds have displayed intriguing potential in the antibiotic discovery setting. Herein, we report unprecedented introduction moiety such as an aryl boronic acid external region oxazolidinone structure via chemoselective acyl coupling reaction. As result, accessed series analogues with distal pharmacophore on scaffold. We identified that peripheric linear conformation coupled freedom rotation and no further substitution ring, amido linkage hydrogen bonding character, addition to para-relative disposition between group linker, are optimal combination structural features this antimicrobial activity. In comparison linezolid, analogue comprising all those features, compound 20b, levels activity augmented eight-fold thirty-two-fold against panel strains, near one hundred-fold Escherichia coli JW5503, Gram-negative mutant strain defective efflux capability.