Antibiotic resistance is a threat being faced globally, particularly in the United States, and is often the result of the overuse of antibiotics. One promising method that could potentially be used in place of antibiotics is the use of “nonantibiotic” synthetic molecules that interfere with quorum sensing (QS). The use of acetophenone and its analogues for the syntheses of β-ketoesters and β-ketoamides remains a promising synthetic route to inhibit QS in various strands of Gram-negative bacteria. In this study, a library of acetophenones was tested for its reactivity in β-ketoester reactions to optimize overall yields. The functional group and regiochemistry of the β-ketoester library were analyzed to determine the impact on retention time, yield, and UV-Vis properties during purification using a Biotage Automated Flash Chromatography System. These data were compared to properties calculated computationally for the library in order to further understand the effects of polarity and regiochemistry on product yields, as well as trends associated with the effects of polarity on retention time and on UV-Vis properties. Results from this study will provide predictive trends to enhance scale-up reactions in the production of final QS inhibitor analogues required for biological testing.

Observing the effects of polarity, functional group, and regiochemistry on the synthesis of β-Ketoesters, key intermediates of quorum sensing inhibitors

ACS Spring Meeting 2021

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