title: Total Synthesis of Fijiolide A.
abstract: Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete of the genus Nocardiopsis. It was found to significantly reduce the TNF-α induced activity of the transcription factor NFκB, which is considered a promising target for the treatment of cancer and inflammation-related diseases. We disclose an enantioselective synthesis of fijiolide A enabled by a fully intermolecular, yet regioselective cyclotrimerization of three unsymmetrical alkynes to construct its tetra-substituted arene core. An atropselective macroetherification enables the assembly of the strained [2.6]paracyclophane motif. A late-stage glycosylation of the macrocyclic aglycone at its tertiary alcohol position allowed for the first total synthesis of fijiolide A.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne EPFL SB ISIC LCSA BCH 4305 CH-1015 Lausanne, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heinz
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne EPFL SB ISIC LCSA BCH 4305 CH-1015 Lausanne, Switzerland. nicolai.cramer@epfl.ch.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Cramer
mesh_terms: D000192:Actinomycetales / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D006027:Glycosides / Q000138:chemical synthesis* / Q000302:isolation & purification; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D006027:Glycosides; C550822:fijiolide A; D012428:Ruthenium