Heinz, ChristophCramer, Nicolai2016-07-192016-07-192016-07-19201610.2533/chimia.2016.258https://infoscience.epfl.ch/handle/20.500.14299/127987WOS:000375350900006Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete of the genus Nocardiopsis. It was found to significantly reduce the TNF-alpha induced activity of the transcription factor NF kappa B, 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.[2+2+2] CycloadditionFijiolideGlycosylationParacyclophane formationTotal synthesistext::journal::journal article::research article