Antibacterials: Synthesis And Structure-activity Studies of 3-aryl-2-oxooxazolidines. 1. The “B” Group

Abstract

The synthesis and structure/activity studies of the effect of varying the ''B” group in a series of oxazolidinone antibacterials (I) are described. Two synthetic routes were used: (1) alkylation of aniline with glycidol followed N 0 0 A VB I by dialkyl carbonate heterocyclization to afford I (A = H, B = OH), whose arene ring was further elaborated by using electrophilic aromatic substitution methodology; (2) cycloaddition of substituted aryl isocyanates with epoxides to give A and B with a variety of values. I with B = OH or Br were converted to other “B” functionalities by using sn 2methodology. Antibacterial evaluation of compounds I with A = acetyl, isopropyl, methylthio, methylsulfinyl, methylsulfonyl, and sulfonamido and a variety of different “B” groups against Staphylococcus aureus and Enterococcus faecalis concluded that the compounds with B = aminoacyl, and particularly acetamido, were the most active of those examined in each A series, possessing MICs in the range of 0.5-4 μg/mL for the most active compounds described. © 1989, American Chemical Society. All rights reserved.