Stereoselective synthesis of a natural product inspired tetrahydroindolo[2,3-a]-quinolizine compound library

Bioorg Med Chem. 2015 Jun 1;23(11):2614-20. doi: 10.1016/j.bmc.2015.01.019. Epub 2015 Jan 17.

Abstract

A natural product-inspired synthesis of a compound collection embodying the tetrahydroindolo[2,3-a]quinolizine scaffold was established with a five step synthesis route. An imino-Diels-Alder reaction between Danishefsky's diene and the iminoesters derived from tryptamines was used as a key reaction. Reductive amination of the ketone function and amide synthesis with the carboxylic acid derived from the ethyl ester, were used to decorate the core scaffold. Thus a compound library of 530 tetrahydroindolo[2,3-a]quinolizines was generated and submitted to European lead factory consortium for various biological screenings.

Keywords: Compound library; Imino-Diels–Alder reaction; Indole alkaloids; Indoloquinolizines; Stereoselective reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemical synthesis*
  • Cycloaddition Reaction
  • Drug Discovery*
  • Indoles / chemistry*
  • Molecular Structure
  • Quinolizines / chemistry*
  • Small Molecule Libraries / chemical synthesis*
  • Stereoisomerism

Substances

  • Biological Products
  • Indoles
  • Quinolizines
  • Small Molecule Libraries