Synthesis of new 1,4-and 1,5-disubstituted N-ethyl acetate and N--butyro--lactone alkylimidazole derivatives as N-acylhomoserine lactone analogs

New alkylimidazoles functionalized with a homoserine lactone or an alkyloxycarbonyl moiety have been synthesized as N-acylhomoserine lactones (AHLs) analogs. The 1,4-disubstituted imidazole derivatives were prepared by alkylation of 4(5)-alkylimidazoles with alpha-bromo-gamma-butyrolactone or ethyl alpha-bromoacetate. An alternative route was preferred for the synthesis of their 1,5-disubstituted counterparts based on the use of a N-1-protected alkylimidazole, its alkylation to an N-3-imidazolyl-alpha-acetate and deprotection to the desired 1,5-disubstituted esters and subsequent alkylation of the acetate moiety with cyclic ethylene sulfate followed by acid-catalyzed cyclization. The ability to modulate bacterial quorum sensing of all new compounds was compared to that of previously reported AHL analogs in which the amide bond is replaced by a heterocyclic group.