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 (5) as the starting material is described. Our methodology involved the protonation of samin (5) 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-1 NMR and computational calculations, that is, the diastereomeric alpha- and beta-products were equally formed through the S(N)1-like mechanism, while the beta-product was gradually transformed via an S(N)2-like mechanism to the alpha-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against alpha-glucosidases and free radicals, the lignans 7f and 7o of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the alpha-glucosidase inhibition of 7f and 7o were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both 7f and 7o possessed promising antidiabetic activity, while simultaneously inhibiting alpha-glucosidases and free radicals.
