edoc

A ring-closing metathesis (RCM)-based approach to mycolactones A/B

Gersbach, P. and Jantsch, A. and Feyen, F. and Scherr, N. and Dangy, J. P. and Pluschke, G. and Altmann, K. H.. (2011) A ring-closing metathesis (RCM)-based approach to mycolactones A/B. Chemistry : a European journal, Vol. 17, H. 46. S. 13017-13031.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6002093

Downloads: Statistics Overview

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
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Pluschke, Gerd
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Wiley-VCH Verlag
ISSN:0947-6539
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:08 Nov 2012 16:22
Deposited On:08 Nov 2012 16:13

Repository Staff Only: item control page