title: Total Synthesis of the Glycosylated Macrolide Antibiotic Fidaxomicin.
abstract: The first enantioselective total synthesis of fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is reported. This novel glycosylated macrolide antibiotic is used in the clinic for the treatment of Clostridium difficile infections. Key features of the synthesis involve a rapid and high-yielding access to the noviose, rhamnose, and orsellinic acid precursors; the first example of a β-selective noviosylation; an effective Suzuki coupling of highly functionalized substrates; and a ring-closing metathesis reaction of a noviosylated dienoate precursor. Careful selection of protecting groups allowed for a complete deprotection yielding totally synthetic fidaxomicin.
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
authors.forename: Elias
authors.initials: E
authors.lastname: Kaufmann
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Hattori
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyatake-Ondozabal
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Gademann
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects; D003015:Clostridium Infections / Q000188:drug therapy*; D000077732:Fidaxomicin; D006031:Glycosylation; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D014640:Vancomycin / Q000737:chemistry*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D018942:Macrolides; D014640:Vancomycin; D000077732:Fidaxomicin