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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

Synthesis and Reactivity of Dihalofuranones

Author(s): Thérèse A. Lyons, Cormac G.M. Gahan and Timothy P. O'Sullivan*

Volume 19, Issue 8, 2022

Published on: 18 January, 2022

Page: [662 - 667] Pages: 6

DOI: 10.2174/1570178618666211027103633

Price: $65

Abstract

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, halogenated 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 iodinecontaining dihalofuranones were successfully developed. Suzuki couplings of gem-dihalofuranones were found to proceed with high stereoselectivity.

Keywords: Quorum sensing, autoinducers, resistance, heterocycles, dihalofuranones, Suzuki coupling.

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