Design, Synthesis, Structural, and Computational Studies of (Z)-2,2′,4,4′,5,5′-Hexahydroxy Stilbene as a Potential Antifungal Agent

Stilbenes are a large class of plant-derived secondary metabolites belonging to the polyphenol family and are widely distributed in foods such as grapes, peanuts, and other dietary sources. They exist in two isomeric forms— trans -stilbene (E-form) and cis -stilbene (Z-form)—with several natural derivatives, including resveratrol, pterostilbene, and combretastatin A-4 (a polymethoxylated cis -stilbene), exhibiting a broad spectrum of biological activities such as antimicrobial, anticancer, anti-inflammatory, cardioprotective, neuroprotective, and antidiabetic effects. The cis -stilbene configuration, in particular, offers distinct structural and electronic characteristics that make it highly valuable in the fields of photochemistry, materials science, and medicinal chemistry. In the present work, we report the synthesis of cis -stilbene derivative, (Z)-2,2′,4,4′,5,5′-hexahydroxy stilbene, achieved for the first time in a single-step demethylation reaction from its precursor, (Z)-2,2′,4,4′,5,5′-hexamethoxy stilbene. The structure and purity of the synthesized compound were confirmed using Fourier-transform infrared (FTIR) spectroscopy, mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy, including both ¹H and ¹³C NMR. The Z-configuration and detailed molecular structure were further validated through single-crystal X-ray diffraction analysis. In addition to structural characterization, density functional theory (DFT) studies were conducted to understand the molecule’s electronic properties, which complemented the experimental data.