Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete and displays inhibitory activity against TNF-alpha-induced activation of NF kappa B, an important transcription factor and a potential target for the treatment of different cancers and inflammation related diseases. Fijiolide A is a glycosylated complex paracyclophane, which is structurally closely related to the Bergman-aromatization product of enediyne C-1027. We report an enantioselective synthesis of fijiolide A demonstrating the power of fully intermolecular ruthenium-catalyzed [2 + 2 + 2]-cyclotrimerizations with three different alkynes to assemble the heavily substituted central arene core. The characteristic strained [2.6]-paracydophane structure is accessed by a templated atropselective macroetherification reaction.