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

Qiang Zhang , Si-Zhe Li , Yves Queneau (1) , Laurent Soulère

1 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

New alkylimidazoles functionalized with a homoserine lactone or an alkyloxycarbonyl moiety have been synthesized as N-acylhomoserine lactones (AHL) analogues. The 1,4-disubstituted imidazole derivatives were prepared by alkylation of 4(5)alkylimidazoles with α-bromo-γ-butyrolactone or ethyl α-bromoacetate. An alternative route was preferred for the synthesis of their 1,5-disubstituted counterparts based on the use of a N1protected alkylimidazole, its alkylation to an N3-imidazolyl-α-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 analogues in which the amide bond is replaced by a heterocyclic group.

Mots clés: Imidazole; bioisostere; AHL analogue; Quorum sensing

Domaines: Chimie

Qiang Zhang, Si-Zhe Li, Yves Queneau, Laurent Soulère. Synthesis of new 1,4‐ and 1,5‐disubstituted N ‐ethyl acetate and N ‐α‐butyro‐γ‐lactone alkylimidazole derivatives as N ‐acylhomoserine lactone analogs. Journal of Heterocyclic Chemistry, inPress, ⟨10.1002/jhet.4356⟩. ⟨hal-03378482⟩