title: Total synthesis of the protected aglycon of fidaxomicin (tiacumicin B, lipiarmycin A3).
abstract: Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18-membered macrolactone is reported herein. The key reactions include ring-closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium-sized fragments, thus leading to a flexible yet convergent synthetic route.
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland) http://www.chemie.unibas.ch/∼gademann.
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyatake-Ondozabal
authors.forename: Elias
authors.initials: E
authors.lastname: Kaufmann
authors.forename: Karl
authors.initials: K
authors.lastname: Gademann
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D000077732:Fidaxomicin
chemical_list: D000617:Aminoglycosides; D000077732:Fidaxomicin
keywords: antibiotics; cross coupling; natural products; stereoselective synthesis