Synthesis of brominated isobenzofuranones as new potent inhibitors of quorum sensing

Abstract

We designed and synthesized a series of brominated isobenzofuranone derivatives. These Compounds have significant biofilm inhibitory activities and are good candidates for quorum sensing inhibitors (QSIs). All of them can be synthesized simply within two steps. The optimization of the first step, gem-dibromoolefination of phthalic anhydride, was done by replacing PPh3 with P(Oi-Pr)3 and adding Zn dust, which significantly increased the reaction yields. After Stille coupling of an aryltin compound with the dibrominated furanone (A), a Z form isomer was obtained as a major product. The formation of the Z isomer was confirmed by 1H NMR spectroscopy and also single-crystal X-ray diffraction. According to the chemistry developed, a series of aryl-substituted bromofuranones were prepared and tested against quorum sensing inhibition. Out of these compounds tested, phenyl-substituted compound proved to be the most active one.