Total and semi-syntheses of antimicrobial thuggacin derivatives

authored by

Jana Franke, Martin Bock, Richard Dehn, Jörg Fohrer, Santosh B. Mhaske, Antonella Migliorini, Argyrios A. Kanakis, Rolf Jansen, Jennifer Herrmann, Rolf Müller, Andreas Kirschning

Abstract

The total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A-C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi-synthetic O-methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17-C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.

Organisation(s)

Institute of Organic Chemistry
Centre of Biomolecular Drug Research (BMWZ)

External Organisation(s)

CSIR Indian Institute of Chemical Technology
Helmholtz Centre for Infection Research (HZI)
Saarland University

Type

Article

Journal

Chemistry - A European Journal

Volume

21

Pages

4272-4284

No. of pages

13

ISSN

0947-6539

Publication date

04.02.2015

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Catalysis, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1002/chem.201405874 (Access: Closed)