Novel 1,3‐Dithiol‐Linked Vanillin Derivatives: Synthesis, Spectral, Structural Characterization, and In Vitro Anti‐Alzheimer, Antidiabetic Evaluation

Abstract

ABSTRACT In this work, we report the first crosslinking of vanillin with various 1,3‐dithiol‐2‐yl derivatives bearing a wide range of side groups. This original class of vanillinated dithiole molecules was synthesized using a simple one‐pot substitution method in a phosphite medium, involving the desulfurization of 1,3‐dithiol‐2‐thione and a hydrogen transfer from the C5‐position of 4‐hydroxy‐3‐methoxybenzaldehyde to the C2’‐position of the dithiole ring. The new molecules were identified by spectroscopic techniques including FT‐IR, UV–vis, 1 H NMR, 13 C NMR, and 2D NMR ( 1 H‐ 13 C HSQC and HMBC), as well as high‐resolution mass spectrometry (HMRS). Electrochemical behavior was also studied using cyclic voltammetry. Furthermore, the structures were confirmed by x‐ray crystallography. Total electron density, allowing identification of electrophilic and nucleophilic regions. These newly synthesized vanillin derivatives exhibited neuroprotective activity relevant to the management of Alzheimer's disease and demonstrated antidiabetic potential.