Total and semi-syntheses of antimicrobial thuggacin derivatives

verfasst von

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.

Organisationseinheit(en)

Institut für Organische Chemie
Zentrum für Biomolekulare Wirkstoffe (BMWZ)

Externe Organisation(en)

CSIR Indian Institute of Chemical Technology
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Universität des Saarlandes

Typ

Artikel

Journal

Chemistry - A European Journal

Band

21

Seiten

4272-4284

Anzahl der Seiten

13

ISSN

0947-6539

Publikationsdatum

04.02.2015

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Katalyse, Organische Chemie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1002/chem.201405874 (Zugang: Geschlossen)