Design, Synthesis, Theoretical Study, and Antioxidant Activity of Aromaticity-Extended Resveratrol Derivatives Incorporating Chalcogen

Naturally occurring antioxidants have attracted significant research interest, owing to their radical scavenging ability that can be improved via structural modifications. In this study, aromaticity-extended resveratrol analogues (<b>3</b>-<b>5</b>) containing chalcogens were designed and synthesized using ring closure and Horner-Wadsworth-Emmons reactions. The antioxidant activities of the derivatives were evaluated using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABST) assay. All resveratrol derivatives (<b>3</b>-<b>5</b>) exhibited higher radical scavenging activities than resveratrol <b>1</b> and analogue <b>2</b>, with benzoselenophene-conjugated derivative <b>5</b> demonstrating the highest activity. The improved antioxidant performance of the resveratrol derivatives was attributed to the extended π conjugation resulting from the incorporation of fused rings, benzoheteroles. Additionally, the integration of benzoheteroles into resveratrol contributed to an efficient reduction in HOMO-LUMO gaps. This study demonstrates that aromaticity extension by introducing benzofuran, benzothiophene, and benzoselenophene is a feasible strategy for improving the antioxidant activity of naturally occurring oxidants.