Photocatalytic Unsymmetrical Coupling of 2-Substituted Quinolines: Synthesis and Evaluation of the Antiplasmodial Potential of β-Norbenzomorphan Frameworks
Inder Kumar, Shiv Shankar Gupta, Rakesh Kumar, Rohit Kumar, Prakhar Agrawal, Dinkar Sahal, Upendra Sharma
Abstract
We herein report unsymmetrical coupling of 2-methylquinolines under the blue LED light conditions using iridium-based photocatalyst. This methodology represents the direct synthetic method for the β-norbenzomorphan skeleton from the quinoline moiety. The current method is more ecofriendly and efficient compared to the existing methods as manifested by green metrics parameters. Substituted quinolines gave the desired products with good to excellent yields. In vitro study of isolated compounds against the growth of Plasmodium falciparum grown in human red blood cells using SYBR green microtiter plate-based screening showed 2d (chlorine-substituted imitate) and 2o (CO2Et-substituted imitate) to have sub-micromolar IC50s against chloroquine-resistant PfINDO strain. In silico docking scores for binding to falcipain-2 were comparable (2d) or better (2o) than chloroquine.