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DOI: 10.1055/s-0043-1763717
Synthesis of (±)-Gelsemine
The Total Synthesis of (±)-Gelsemine.
J. Chem. Soc., Chem. Commun. 1994; 767-768
DOI: 10.1039/C39940000767
Significance
Speckamp, Hiemstra, and co-workers present the first total synthesis of gelsemine, an oxindole alkaloid isolated from Gelsemium sempervirens in 1870. Investigation of the biological activity identified gelsemine as a potent glycine receptor agonist, which exhibits significantly higher binding affinity for some of these receptors than their native agonist, glycine. Hence, gelsemine is a highly toxic substance and to this day no antidote has been found.
Comment
Adduct C is readily accessed through an endo-selective Diels–Alder reaction of diene A and malimide B. Intramolecular N-acyliminium cyclization forges the bridged tricyclic core in H. Pd-mediated carbonylative coupling of vinyl triflate I and 2-bromoaniline paves the way for a subsequent Heck cyclization to install the quaternary spirocenter in K. Hg(OTf)2-promoted oxymercuration and organomercurial reduction followed by global deprotection conclude the synthesis of (±)-gelsemine.
Publication History
Article published online:
15 April 2024
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