Mohamed Boukraa

N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), regulates various gene expressions, including growth, virulence, biofilms formation, and toxin production. Considering the role of QS in bacterial pathogenicity, its modulation appears as a possible complementary approach in antibacterial strategies. Analogues and mimics of AHLs are therefore biologically relevant targets, including several families in which heterocyclic chemistry provides a strategic contribution in the molecular design and the synthetic approach. AHLs consist of three main sections, the homoserine lactone ring, the central amide group, and the side chain, which can vary in length and level of oxygenation. The purpose of this review is to summarize the contribution of heterocyclic chemistry in the design of AHLs analogues, insisting on the way heterocyclic building blocks can serve as replacements of the lactone moiety, as a bioisostere for the amide group, or as an additional pattern appended to the side chain. A few non-AHL-related heterocyclic compounds with AHL-like QS activity are also mentioned.

The monoacylhydrazides, as well as hydrazines, react with phosphoallenic derivatives 1 to lead to the δ⁵-N-2 acyl 3-dimethylamino 3-oxo-1,2,3-diazaphospholine 2 . The reaction of ring opening in δ⁵-N-2 acyl-3-dimethylamino-3-oxo-1,2,3-diazaphospholine by different alcohols leads to the β-phosphonyl-hydrazide 3 . The structure of products ( 2 and 3 ) is further confirmed by IR, ¹H, NMR, ¹³P NMR, ¹³C NMR spectra.