Total Synthesis of Tetrodotoxin

Angew Chem Int Ed Engl. 2020 Apr 6;59(15):6253-6257. doi: 10.1002/anie.201916611. Epub 2020 Feb 19.

Abstract

A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which was used to construct the remaining stereogenic centers. A nitrogen atom was introduced either by a four-step sequence involving a Curtius rearrangement, or a three-step sequence featuring a newly developed transformation of a terminal alkyne into a nitrile. Introduction of the guanidine moiety followed by the formation of the heterocyclic system by cascade reactions led to tetrodotoxin.

Keywords: Diels-Alder reaction; guanidines; natural products; rearrangements; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Chemistry Techniques, Synthetic
  • Guanidine / chemistry
  • Nitriles / chemistry
  • Nitrogen / chemistry
  • Tetrodotoxin / chemical synthesis*
  • Tetrodotoxin / chemistry

Substances

  • Alkynes
  • Nitriles
  • Tetrodotoxin
  • Guanidine
  • Nitrogen