Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity

Org Biomol Chem. 2016 Jul 7;14(25):5951-5. doi: 10.1039/c6ob01083k. Epub 2016 Jun 3.

Abstract

A novel method for the preparation of 2-carboxyl-3-aryl quinoline derivatives from anilines, ethyl glyoxalate and enol ethers as phenylacetaldehyde surrogates is reported. The three-component coupling reaction occurs rapidly under mild conditions in dichloromethane catalysed by TFA. The method allows a more direct access to 3-aryl quinolines, sidestepping issues encountered with phenylacetaldehyde derivatives. This chemistry was used to prepare quinolines with 3-diarylether functionality that showed low micromolar efficacy (IC50 range: 5-26 μM) against in vitro Toxoplasma gondii coupled with little or no cytotoxicity (TD50≥ 320 μM) towards the host cells.

MeSH terms

  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Ethers / chemistry*
  • Glyoxylates / chemistry
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Toxoplasma / drug effects*

Substances

  • Antiprotozoal Agents
  • Ethers
  • Glyoxylates
  • Quinolines
  • ethyl glyoxalate