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Synfacts 2016; 12(3): 0221
DOI: 10.1055/s-0035-1561233
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Gelsenicine

Authors

    Contributor(s):

  • Erick M. Carreira

  • Marco Brandstätter

Newcomb ET, Knutson PC, Pedersen BA, Ferreira EM * University of Georgia, Athens, USA
Total Synthesis of Gelsenicine via a Catalyzed Cycloisomerization Strategy.

J. Am. Chem. Soc. 2016;
138: 108-111
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Further Information

Publication History

Publication Date:
16 February 2016 (online)

 
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Key words

gelsenicine - cycloisomerization - Cope rearrangement - gold

Significance

Gelsenicine is an oxindole alkaloid isolated from Gelsemium Elegans, a toxic plant widely distributed in Southeast Asia and used in traditional Chinese medicine. The structure features an oxabicyclo[3.3.2] system, an oxindole, and a pyrroline. Ferreira and co-workers disclose the first total synthesis of gelsenicine relying on a gold-mediated cycloisomerization followed by a Cope rearrangement that enabled the quick construction of the gelsenicine core.


Comment

Cycloisomerization precursor D was prepared from known aldehyde A using Horner–Wadsworth–Emmons olefination followed by ­Cadiot–Chodkiewicz coupling. Upon exposure to [Au(JohnPhos)(MeCN)SbF6] (E), D underwent cycloisomerization to F. Heat-induced cis/trans isomerization and subsequent Cope rearrangement provided G. HgSO4-mediated regioselective alkyne hydration followed by oxindole and radical pyrroline formation culminated in the synthesis of gelsenicine in 13 steps and 4.2% overall yield.





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