Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer

Tian Qin, Sarah L. Skraba-Joiner, Zeinab G. Khalil, Richard P. Johnson, Robert J. Capon, John A. Porco

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Abstract

Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2′-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.

Original languageEnglish (US)
Pages (from-to)234-240
Number of pages7
JournalNature Chemistry
Volume7
Issue number3
DOIs
StatePublished - Mar 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Qin, T., Skraba-Joiner, S. L., Khalil, Z. G., Johnson, R. P., Capon, R. J., & Porco, J. A. (2015). Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer. Nature Chemistry, 7(3), 234-240. https://doi.org/10.1038/nchem.2173