Configurationally Stabilized Analogs of M. ulcerans Exotoxins Mycolactones A and B Reveal the Importance of Side Chain Geometry for Mycolactone Virulence

Mycolactones A/B (1a/b) are exotoxins of Mycobacterium ulcerans that are the molecular cause of Buruli ulcer. 1a/b represent a rapidly equilibrating mixture of Z/E isomers about the C4′C5′ double bond of the C5-side chain. Here, we describe the syntheses of mycolactone analogs with configurationall...

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Bibliographic Details
Published in:Organic letters 2019-08, Vol.21 (15), p.5853-5857
Main Authors: Gehringer, Matthias, Mäder, Patrick, Gersbach, Philipp, Pfeiffer, Bernhard, Scherr, Nicole, Dangy, Jean-Pierre, Pluschke, Gerd, Altmann, Karl-Heinz
Format: Article
Language:English
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Summary:Mycolactones A/B (1a/b) are exotoxins of Mycobacterium ulcerans that are the molecular cause of Buruli ulcer. 1a/b represent a rapidly equilibrating mixture of Z/E isomers about the C4′C5′ double bond of the C5-side chain. Here, we describe the syntheses of mycolactone analogs with configurationally stable C5-side chains (2a, E mimetic; 2b/c, Z mimetics). Based on the cytotoxicity of 2a–c, the Δ4′,5′-trans isomer of mycolactones A/B (1b) appears to be the major virulence factor.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.9b01947