Thioether and Ether Furofuran Lignans: Semisynthesis, Reaction Mechanism, and Inhibitory Effect against α-Glucosidase and Free Radicals.

The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin () as the starting material is described. Our methodology involved the protonation of samin () to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring H NMR and computational calculations, that is, the diastereomeric α- and β-products were equally formed through the S1-like mechanism, while the β-product was gradually transformed via an S2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans and of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of and were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both and possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals.