The emergence of bacterial resistance to known antimicrobials and phytosanitaries is currently one of the main health and food security problems. Therefore, the WHO and the FAO have stressed that the development of new antimicrobials and other drugs to face this challenge is urgently needed. A promising strategy is the development of quorum sensing (QS) modulators, molecules that interfere with the bacterial communication needed for their coordinated actions, such as host invasion, virulence, or the formation of biofilms. One advantage of this strategy is that the microorganisms are not killed, and thus the evolutive pressure towards resistance is greatly reduced. Bacteria use specific chemical signals called autoinducers to communicate. Among them, Gram-negative bacteria use N-Acyl Homoserine Lactones (AHL). Since Gram-negative pathogens are responsible of many of the most dangerous animal and plant infections, different groups have developed AHL analogues that could serve as QS inhibitors. This communication describes a synthetic methodology to readily prepare AHL analogues in order to create libraries for structure-bioactivity studies. The process involves a radical scission of hydroxyproline “customizable” units (1) and subsequent reduction of the intermediate (2) to afford AHL derivatives (3) as QSI candidates.

Synthesis of N-acyl homoserine lactone analogues as potential quorum sensing modulators

ACS Spring Meeting 2021

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