L-Proline-catalysed synthesis of chromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione and an anti-proliferative study.

Abstract

The reactivity of 4-hydroxy-2H-chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3-b]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.