1521-3765/asset/2111_left.gif?v=1&s=0561086440e3dfc935e925fa17e4b4c8a50bbfe3)
1521-3765/asset/2111_right.gif?v=1&s=9fa3626b72da80da2a89f547de4d2cc5d7fadfe6)
Full Paper
A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins
Article first published online: 30 NOV 2011
DOI: 10.1002/chem.201102542
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Chany, A.-C., Casarotto, V., Schmitt, M., Tarnus, C., Guenin-Macé, L., Demangel, C., Mirguet, O., Eustache, J. and Blanchard, N. (2011), A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins. Chem. Eur. J., 17: 14413–14419. doi: 10.1002/chem.201102542
Publication History
- Issue published online: 14 DEC 2011
- Article first published online: 30 NOV 2011
- Manuscript Received: 16 AUG 2011
Funded by
- CNRS
- GlaxoSmithKline
- Agence Nationale de la Recherche. Grant Number: 07-MIME-016-03
- Raoul Follereau foundation
- Roche
Keywords:
- Buruli ulcer;
- metathesis;
- mycolactones;
- structure–activity relationships;
- total synthesis
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.