Synthesis of Fijiolide A via an Atropselective Paracyclophane Formation.

Abstract

Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete and displays inhibitory activity against TNF-α-induced activation of NFκB, 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]paracyclophane structure is accessed by a templated atropselective macroetherification reaction.

• Authors: Christoph Heinz, Nicolai Cramer
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 137 Issue 35 Pg. 11278-81 (Sep 09 2015) ISSN: 1520-5126 [Electronic] United States
• PMID: 26301726 (Publication Type: Journal Article)