A Scalable Total Synthesis of the Antitumor Agents Et-743 and Lurbinectedin

Angew Chem Int Ed Engl. 2019 Mar 18;58(12):3972-3975. doi: 10.1002/anie.201900035. Epub 2019 Feb 14.

Abstract

An efficient and scalable approach is described for the total synthesis of the marine natural product Et-743 and its derivative lubinectedin, which are valuable antitumor compounds. The method delivers 1.6 % overall yield in 26 total steps from Cbz-protected (S)-tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light-mediated remote C-H bond activation to assemble a benzo[1,3]dioxole-containing intermediate.

Keywords: C−H bond activation; antitumor agents; cyclization; marine natural products; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Carbolines / chemical synthesis*
  • Carbolines / chemistry
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Stereoisomerism
  • Trabectedin / chemical synthesis*
  • Trabectedin / chemistry
  • Tyrosine / chemistry

Substances

  • Antineoplastic Agents
  • Carbolines
  • Heterocyclic Compounds, 4 or More Rings
  • PM 01183
  • Tyrosine
  • Trabectedin