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Synthesis and reactivity of dihalofuranones
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Lyons, Thérèse A.
Gahan, Cormac G. M.
O'Sullivan, Timothy P.
Bentham Science Publishers
Halogenated furanones have been found to act as potent quorum sensing inhibitors in several bacterial species. It is believed that dihalofuranones covalently bind to the LuxS enzyme, which is necessary for autoinducer-2 synthesis. In addition to their antimicrobial activity, halogen-ated furanones also possess anti-cancer, antioxidant, and depigmentation properties. However, traditional routes to these compounds are low-yielding and capricious. The aim of this study was to investigate higher-yielding preparations of gem-dihalofuranones and compare their reactivity using Suzuki chemistry. Ramirez dibromoolefination of maleic anhydride was optimised using a variety of conditions. A similar route was investigated for the preparation of bromofluorofuranones and dichlorofuranones. The conversion of a dichlorofuranone to the corresponding iodofuranone derivatives using microwave-assisted Finkelstein chemistry was also studied. Lastly, the reactivity of the different dihalofuranones was compared by Pd-mediated coupling with phenylboronic acid. A higher-yielding, concise synthesis of dibromofuranones was developed using a modified Ramirez reaction. Additionally, a telescoped preparation of dichlorofuranone was higher yielding than previous approaches. Bromine-and iodine-substituted dihalofuranones proved more reactive than their chlorine-substituted analogues. Higher yielding routes to bromine-, fluorine-, chlorine-and iodine-containing dihalofuranones were successfully developed. Suzuki couplings of gem-dihalofuranones were found to proceed with high stereoselectivity.
Quorum sensing , Suzuki coupling , Autoinducers , Dihalofuranones , Heterocycles , Resistance
Lyons T. A., Gahan C. G. M. and O'Sullivan T. P. (2022) 'Synthesis and reactivity of dihalofuranones', Letters in Organic Chemistry, 19(8), pp. 662-667. doi: 10.2174/1570178618666211027103633
© 2022, Bentham Science Publishers. This is the accepted version of the following item: Lyons T. A., Gahan C. G. M. and O'Sullivan T. P. (2022) 'Synthesis and reactivity of dihalofuranones', Letters in Organic Chemistry, 19(8), pp. 662-667, doi: 10.2174/1570178618666211027103633. The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/10.2174/1570178618666211027103633