Synthesis of borylated-stilbenes under environmentally friendly Wittig reaction and interaction studies with HSA

Abstract

Herein we report the Wittig reaction conducted under environmentally friendly conditions for the synthesis of borylated analogues of resveratrol. For the synthesis of analogues featuring the boronic ester functional group, we developed a micellar aqueous method that yielded borylated-stilbenes in good yields with a low diastereomeric ratio. To circumvent this low selectivity, we employed an isomerization reaction, which provided borylated stilbenes with high selectivities (≥95 : 05). For synthesizing analogues containing the benzoxaborole and boronic acid functional groups, a biphasic toluene-water system emerged as the optimal reaction medium. Three functionalized stilbenes-bearing boronic ester, benzoxaborole, and boronic acid interact with a single binding site on HSA, with the benzoxaborole derivate exhibiting the highest affinity. Based on thermodynamic analysis, boronic ester and the benzoxaborole derivate bind to HSA via hydrophobic interactions, whereas the boronic acid derivate binds via electrostatic forces.