An enantioselective strategy for the synthesis of (S)-tylophorine via one-pot intramolecular Schmidt/Bischler-Napieralski/imine-reduction cascade sequence

J Org Chem. 2013 Mar 15;78(6):2775-9. doi: 10.1021/jo302725q. Epub 2013 Feb 11.

Abstract

A novel enantioselective strategy for the total synthesis of (S)-tylophorine was developed in an overall yield of 48% with more than 99% ee from readily avaliable azido acid and phenanthryl alcohol. This route features an Evans stereoselective alkylation and an unprecedented one-pot intramolecular Schmidt/Bischler-Napieralski/imine-reduction cascade sequence, in which three new bonds and two rings formed in 84% yield. The intramolecular Schmidt rearrangement of the azido aldehyde was proved to be racemization-free.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry*
  • Alkylation
  • Azides / chemistry*
  • Imines / chemistry*
  • Indolizines / chemical synthesis*
  • Indolizines / chemistry*
  • Molecular Structure
  • Phenanthrenes / chemical synthesis*
  • Phenanthrenes / chemistry*
  • Stereoisomerism

Substances

  • Alkaloids
  • Azides
  • Imines
  • Indolizines
  • Phenanthrenes
  • tylophorine