A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins

Abstract

Mycolactones are complex macrolides responsible for a severe necrotizing skin disease called Buruli ulcer. Deciphering their functional interactions is of fundamental importance for the understanding, and ultimately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis approach of mycolactones analogues and provide the first insights into their structure-activity relationship based on cytopathic assays on L929 fibroblasts. The lowest concentration inducing a cytopathic effect was determined for selected analogues, allowing a clear picture to emerge by comparison with the natural toxins.