title: Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity.
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.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada L8S 4M1. jmcnult@mcmaster.ca.
authors.forename: Carla E
authors.initials: CE
authors.lastname: Brown
authors.forename: James
authors.initials: J
authors.lastname: McNulty
authors.forename: Claudia
authors.initials: C
authors.lastname: Bordón
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Lorraine
authors.initials: L
authors.lastname: Jones-Brando
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D004987:Ethers / Q000737:chemistry*; D006038:Glyoxylates / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D004987:Ethers; D006038:Glyoxylates; D011804:Quinolines; C579385:ethyl glyoxalate