Synthesis of LuxS Inhibitors Targeting Bacterial Cell−Cell Communication

Abstract

[reaction: see text] Quorum sensing is a process by which bacteria sense cell density. This cell-cell communication process is mediated by autoinducers. A cross-species messenger, autoinducer-2 (AI-2) is produced from S-ribosyl-L-homocysteine by the LuxS enzyme. A proposed mechanism for LuxS is an aldose-ketose isomerization of S-ribosylhomocysteine followed by a beta-elimination. We report here the synthesis of two substrate analogues, S-anhydroribosyl-L-homocysteine and S-homoribosyl-L-cysteine, which prevent the initial and final step of the mechanism, respectively.