Antibiotic resistance, often caused by the overuse of antibiotics, continues to remain a global threat. “Nonantibiotic” synthetic molecules that interfere with quorum sensing (QS) are a promising method that could potentially be used as an alternative to antibiotics. One potential synthetic method to inhibit QS in strains of Gram-negative bacteria is the use of acetophenone and its analogues for the preparation of β-ketoesters and β-ketoamides. A library of acetophenones was tested for its reactivity in β-ketoester syntheses, the key intermediates of the inhibitors, to optimize overall yields. To determine the impact on retention time, yield, and UV-Vis properties during purification, the functional group and regiochemistry of the β-ketoester library were examined. Properties determined by computational calculations were utilized to analyze the differences and understand the influence of polarity and regiochemistry on the synthesis of β-ketoesters. These β-ketoesters were then used to synthesize the final QS inhibitor analogues, β-ketoamides. The differences in properties of the β-ketoester library were correlated to solubility and stability trends to their corresponding β-ketoamides.

Determining the Impact of polarity, functional group, and regiochemistry on the synthesis and stability of quorum sensing inhibitors

ACS Spring 2022

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