Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Molecules. 2022 Dec 17;27(24):9001. doi: 10.3390/molecules27249001.
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.
芝麻木脂素的转化很有趣，因为衍生产物具有增强的生物活性和广泛的潜在应用。在这项研究中，使用芝麻素（samin()）作为起始原料描述了 28 种呋喃木脂素的半合成。我们的方法涉及 samin()的质子化，以生成氧碳正离子，然后由两种不同的亲核试剂，即硫醇（RSH）和醇（ROH）进攻。得到了高度非对映选择性的硫醚和醚呋喃木脂素，其构型通过 2D NMR 和 X 射线晶体学得到证实。通过监测 1H NMR 和计算计算研究了反应的机理，即通过 S1 样机制同样形成了非对映异构体的α-和β-产物，而β-产物在后期通过 S2 样机制逐渐转化为α-同系物。在评估合成木脂素对α-葡萄糖苷酶和自由基的抑制作用后，酚羟基的木脂素和具有最强的抑制活性。此外，还验证了和对α-葡萄糖苷酶抑制作用的机制分别为混合方式和非竞争性抑制。结果表明，和都具有有前途的抗糖尿病活性，同时抑制α-葡萄糖苷酶和自由基。
