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.

The macrolide ketocarbonic acid carolacton (1) was isolated from the myxobacterium Sorangium cellulosum, strain So ce960, because of its antibiotic activity. Subsequently, carolacton (1) was discovered to be a highly potent agent against biofilms containing the caries- and endocarditis-associated bacterium Streptococcus mutans. The 2D structure of 1 was elucidated by HRMS, IR and 2D NMR spectroscopy. Initially, the stereogenic centres were determined by chemical derivatization in combination with computional methods and finally verified by X-ray analysis.

Der Strukturbeweis für die Thuggacine A–C gelang durch einen hochkonvergenten und flexiblen Totalsyntheseansatz. Schlüsselschritte sind eine substratkontrollierte titanvermittelte Aldolreaktion, eine Kreuzmetathese zur Überführung eines terminalen Alkens in das entsprechende Vinyliodid sowie die Verknüpfung dieses komplexen Vinyliodids mit einem terminalen Alkin in einer Sonogashira-Reaktion.

Chemie und Biologie treffen sich in der Strukturaufklärung der antibiotischen Naturstoffe Thuggacin A (siehe Strukturformel), B und C. Eine Kombination aus chemischer Derivatisierung, NMR-Analyse, Molecular Modeling und bioinformatischer Analyse der Biosynthesegene von Thuggacin ermöglichte die Bestimmung der absoluten Konfiguration aller stereogenen Zentren, einschließlich derjenigen in der Seitenkette.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The enantioselective synthesis of the C1-C5 and C6-C24 fragments of the ripostatins utilize a Negishi coupling, two Nagao acetate aldol reactions followed by a Denmark vinylogous aldol reaction and Stille couplings as key C-C bond forming steps.