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

Mycolactones are complex macrolides responsible for a severe ne- crotizing skin disease called Buruli ulcer. Deciphering their functional in- teractions is of fundamental impor- tance for the understanding, and ulti- mately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis ap- proach 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.