A new route towards fimbrolide analogues: importance of the exomethylene motif in LuxR dependent quorum sensing inhibition

Sixteen analogues of fimbrolides (brominated 3-substituted-5-methylene-2(5H)-furanones), naturally occurring bacterial quorum sensing (QS) inhibitors, were synthesized by a novel sequence. The importance of the methylene group, either brominated or non-brominated, in LuxR-dependent QS inhibition was demonstrated. One of the most active furanone-type QS inhibitors was identified, with an IC50 of 0.6 mu M.