|BOUTON, JAKOB - Ghent University|
|VAN HECKE, KRISTOF - Ghent University|
|VAN CALENBERGH, SERGE - Ghent University|
Submitted to: Beilstein Journal of Organic Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2018
Publication Date: 11/12/2018
Citation: Rasooly, R., Bouton, J., Van Hecke, K., Van Calenbergh, S. 2018. Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus. Beilstein Journal of Organic Chemistry. 14:2822-2828. https://doi.org/10.3762/bjoc.14.260.
Interpretive Summary: Staphylococcus aureus is a prevalent bacterial pathogen causing foodborne diseases that affect about a quarter million persons annually in the United States. To provide alternatives to antibiotics and use quorum sensing inhibitors that interfere with the bacterium cell-to-cell communication and toxin secretion we synthesized seven pyrrolidine-based hamamelitannin analogues. The synthesized compounds were evaluated in a biofilm model but were all inactive.
Technical Abstract: 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.