title: Total and semi-syntheses of antimicrobial thuggacin derivatives.
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.
authors: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany), Fax: (+49) 511-762-3011.
authors: Jana
authors: J
authors: Franke
authors: Martin
authors: M
authors: Bock
authors: Richard
authors: R
authors: Dehn
authors: Jörg
authors: J
authors: Fohrer
authors: Santosh B
authors: SB
authors: Mhaske
authors: Antonella
authors: A
authors: Migliorini
authors: Argyrios A
authors: AA
authors: Kanakis
authors: Rolf
authors: R
authors: Jansen
authors: Jennifer
authors: J
authors: Herrmann
authors: Rolf
authors: R
authors: Müller
authors: Andreas
authors: A
authors: Kirschning
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D018942:Macrolides / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C523033:thuggacin C
keywords: antibiotics; lactones; natural products; synthesis design; total synthesis