title: Total synthesis of bafilomycin A1.
abstract: A convergent synthesis of bafilomycin A(1), a potent inhibitor of V-type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium-catalyzed trans-reduction of the resulting propargylic enyne efficiently installs the required C10-C13 trans,trans-diene subunit, implementing an alternative strategy to traditional palladium-catalyzed cross-coupling strategies. A highly selective oxidation of a secondary hydroxyl group in a triol sets the stage for the completion of the synthesis.
authors.affiliation: ETH Zürich HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Kleinbeck
authors.forename: Gabriela J
authors.initials: GJ
authors.lastname: Fettes
authors.forename: Lee D
authors.initials: LD
authors.lastname: Fader
authors.forename: Erick M
authors.initials: EM
authors.lastname: Carreira
mesh_terms: D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; C040929:bafilomycin A1; D025262:Vacuolar Proton-Translocating ATPases