Design, synthesis and antimicrobial activity of chiral 2-(substituted-hydroxyl)-3-(benzo[d]oxazol-5-yl)propanoic acid derivatives

Chiral 2-(substituted-hydroxyl)-3-(benzo[d]oxazol-5-yl)propanoic acid derivatives were synthesized and their antibacterial activities were evaluated against fungus, Gram-negative and Gram-positive bacteria. In general, these compounds showed in vitro activities against all screened Gram-negative and Gram-positive bacteria, but poor MIC values for fungus Candida albicans. Remarkably, the (S)-configuration-substituted phenoxyl side chain on position 2 of propanoic acid exerted excellent antibacterial activity against all screened bacteria. Preliminary structure–activity studies revealed that the hydrophobic substitutes, para-tert-butyl (11r), para-phenyl (11s) and para-benzyloxy (11t) on the phenoxyl side chain displayed best activities against all Gram-negative and Gram-positive bacteria with MIC values between 1.56 and 6.25 μg/mL.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel 2-(substituted-hydroxyl)-3-(benzo[d]oxazol-5-yl)propanoic acids were synthesized. ► (S)-Configuration substituted-phenoxyl derivatives exerted excellent antibacterial activity. ► Hydrophobic compounds 11r, 11s and 11t shown great activities with MIC = 1.56–6.25 μg/mL.