Enantioselective Total Synthesis of (-)-Zygadenine

J Am Chem Soc. 2023 Sep 20;145(37):20202-20207. doi: 10.1021/jacs.3c08039. Epub 2023 Sep 8.


The Veratrum alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (-)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels-Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the de novo synthesis of this highly oxidized Veratrum alkaloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products*
  • Carbon
  • Cyclization
  • Cycloaddition Reaction
  • Stereoisomerism


  • Biological Products
  • Carbon