Gram-Scale, Seven-Step Total Synthesis of (-)-Colchicine

Org Lett. 2021 Apr 2;23(7):2731-2735. doi: 10.1021/acs.orglett.1c00638. Epub 2021 Mar 18.

Abstract

Herein we report a streamlined, gram-scale total synthesis of (-)-colchicine that takes only 7 easy steps, with an overall yield of 27-36%. To warrant the synthetic efficiency and practicality of (-)-colchicine, we tactically utilized a modified version of a powerful Ir-catalyzed amidation reported by Carreira to install the key chiral C-7 acetamido group, Suzuki and biomimetic phenol oxidative coupling, and Banwell-inspired cyclopropane ring cleavage to construct (-)-colchicine precisely and rapidly. Remarkably, a described strategy also can shorten the synthesis of allocolchicinoid to 4 steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Colchicine / chemical synthesis*
  • Colchicine / chemistry
  • Cyclopropanes / chemistry*
  • Molecular Structure
  • Oxidative Coupling
  • Stereoisomerism

Substances

  • Cyclopropanes
  • cyclopropane
  • Colchicine