Synthesis of LuxS Inhibitors Targeting Bacterial Cell−Cell Communication

Abstract
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 β-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.