Cyclic peptides of natural origin or prepared synthetically have attracted increasing interest in medicinal chemistry. They are often selective towards receptors, stable against enzymatic degradation, and exhibit improved activity profiles against a wide variety of targets.In this work, I focus on syntheses and biological evaluation of cyclic compounds acting as quorum sensing modulators.During a global research expedition, over five hundred marine bacterial strains with antibacterial activity were collected, and two depsipeptides, solonamide A and solonamide B, were isolated,.[1] These inhibit growth of Staphylococcus aureus, one of the main causes of nosocomial infections, by interfering with the agr quorum sensing system.[2]To enable more comprehensive studies, larger amounts of the compounds were needed, and we therefore embarked on the chemical synthesis of solonamides A and B.Solonamides are depsipeptides consisting of a tetrapeptide and a (R)-�-hydroxy acid, with the length of a hydrocarbon side chain differentiating the two compounds.The key synthetic step was the formation of (R)-�-hydroxy acids, which were performed by aldol reactions using chiral auxiliaries. The cyclizations were achieved as macrolactamizations under highly dilute conditions and upon a difficult purification, the depsipeptides were obtained.Activity assays as well as immunological tests were performed showing promising results for solonamide B as an antibacterial agent. Acknowledgments We thank the Lundbeck Foundation for funding.References [1] Mansson, M. et.al., Marine drugs 9, 2537 (2011).[2] Nielsen, A. et.al., Plos One 9, e84992 (2014).

Synthesis and biological evaluation of cyclic peptides acting on the quorum sensing system

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.