Total Synthesis of Fijiolide A

Authors

  • Christoph Heinz Ecole Polytechnique Fédérale de Lausanne EPFL SB ISIC LCSA BCH 4305 CH-1015 Lausanne, Switzerland
  • Nicolai Cramer Ecole Polytechnique Fédérale de Lausanne EPFL SB ISIC LCSA BCH 4305 CH-1015 Lausanne, Switzerland. nicolai.cramer@epfl.ch

DOI:

https://doi.org/10.2533/chimia.2016.258

Keywords:

[2 2 2] cycloaddition, Fijiolide, Glycosylation, Paracyclophane formation, Total synthesis

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-? induced activity of the transcription factor NF?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.

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Published

2016-04-27

How to Cite

[1]
C. Heinz, N. Cramer, Chimia 2016, 70, 258, DOI: 10.2533/chimia.2016.258.