Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity
- 26 May 2016
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 14 (25), 5951-5955
- https://doi.org/10.1039/c6ob01083k
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.Funding Information
- Natural Sciences and Engineering Research Council of Canada
- Stanley Medical Research Institute
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