Synthesis and Biological Evaluation of the Trifluoromethyl Analog of (4S)‐4,5‐Dihydroxy‐2,3‐pentanedione (DPD)

Abstract The asymmetric synthesis of the trifluoromethyl analogue of (4S)‐4,5‐dihydroxy‐2,3‐pentanedione [(4S)‐DPD], the metabolic precursor of the bacterial quorum sensing (QS) autoinducer AI‐2, is described. The trifluoromethyl group was introduced by treating (trifluoromethyl)trimethylsilane with an α‐methylene ester resulting from a Baylis–Hillman reaction between (tert‐butyldimethylsilyloxy)acetaldehyde and a vinylamide derived from Oppolzer’s sultam reagent. The α‐diketonic moiety is formed during the last step by reductive ozonolysis of the hemiketal form of an α‐methylene trifluoromethyl ketone. Biological evaluation shows that this analogue is a weaker inducer of QS in Vibrio harveyi bacteria than DPD. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)