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Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus
- Jakob Bouton, Kristof Van Hecke, Reuven Rasooly, Serge Van Calenbergh
- Beilstein journal of organic chemistry 2018 v.14 no. pp. -
- Staphylococcus aureus, antibacterial properties, biofilm, derivatization, metabolic inhibitors, nitrogen, polyphenols, pyrrolidines, quorum sensing, tannins
- Interfering with bacterial cell-to-cell communication is a promising strategy to combat antimicrobial resistance. The natural product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was developed and delivered the pyrrolidine analogue in 17 steps in high yield. Chemoselective derivatization of the pyrrolidine nitrogen atom resulted in 6 more compounds. The synthesized compounds were evaluated in a biofilm model, but were all inactive.