A ring-closing metathesis (RCM)-based approach to mycolactones A/B
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1022805
Author(s) Altmann, K. H.
Author(s) at UniBasel Pluschke, Gerd
Year 2011
Title A ring-closing metathesis (RCM)-based approach to mycolactones A/B
Journal Chemistry : a European journal
Volume 17
Number 46
Pages / Article-Number 13017-13031
Keywords Buruli ulcer, metathesis, mycolactones, natural products, total synthesis
Abstract The total synthesis of the mycobacterial toxins mycolactones A/B (1 a/b) has been accomplished based on a strategy built around the construction of the mycolactone core through ring-closing metathesis. By employing the Grubbs second-generation catalyst, the 12-membered core macrocycle of mycolactones, with a functionalized C2 handle attached to C11, was obtained in 60-80 % yield. The C-linked upper side chain (comprising C12-C20) was completed by a highly efficient modified Suzuki coupling between C13 and C14, while the attachment of the C5-O-linked polyunsaturated acyl side chain was achieved by Yamaguchi esterification. Surprisingly, a diene containing a simple isopropyl group attached to C11 could not be induced to undergo ring-closing metathesis. By employing fluorescence microscopy and flow cytometry techniques, the synthetic mycolactones A/B (1 a/b) were demonstrated to display similar apoptosis-inducing and cytopathic effects as mycolactones A/B extracted from Mycobacterium ulcerans. In contrast, a simplified analogue with truncated upper and lower side chains was found to be inactive
Publisher Wiley-VCH Verlag
ISSN/ISBN 0947-6539
edoc-URL http://edoc.unibas.ch/dok/A6002093
Full Text on edoc No
Digital Object Identifier DOI 10.1002/chem.201101799
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/21971832
ISI-Number WOS:000297737900027
Document type (ISI) Article

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