Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Faculty of Pharmacy, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.
J Org Chem. 2024 Oct 18;89(20):15026-15040. doi: 10.1021/acs.joc.4c01756. Epub 2024 Oct 5.
The Ferrier rearrangement was utilized to obtain 2,3-unsaturated diosgenyl glycosides. This reaction proceeded with high stereoselectivity, yielding mostly saponins with an α configuration (hexoses) or predominantly with a β configuration (pentoses). The diversity of the glycals used and the glycosides obtained enabled a deep discussion of the Ferrier rearrangement mechanism. The mechanism was supported by DFT calculations concerning the intermediate ions. It was concluded that the vinylogous anomeric effect may influence the reactivity of the glycals. Two possible Ferrier rearrangement intermediates, dioxolenium and allyloxycarbenium ions, were hypothesized to exist in thermodynamic equilibrium that shifted toward the former. The allyloxycarbenium ion participates in the final rearrangement step and determines the reaction regioselectivity. Furthermore, the conformational stability of the 2,3-unsaturated pyranose ring determines the stereoselectivity of the reaction. Factors influencing this stability, as well as the NMR data enabling recognition of the H and H conformations, were identified. Chemoselective hydrogenation of 2,3-unsaturated diosgenyl glycosides provided a series of 2,3-dideoxy analogues. The anticancer, hemolytic, and antibacterial activities of the synthesized saponins are presented alongside a discussion of the structure-activity relationships.
利用费里尔重排反应得到 2,3-不饱和薯蓣皂苷配基。该反应具有高度的立体选择性，主要生成具有α构型（己糖）或主要具有β构型（戊糖）的皂苷。所使用的糖醛和获得的糖苷的多样性使得可以深入讨论费里尔重排反应机制。该机制得到了涉及中间体离子的 DFT 计算的支持。结论是，烯醇式端基效应可能影响糖醛的反应性。两种可能的费里尔重排中间体，二氧戊环翁离子和烯丙氧基碳正离子，被假设在热力学平衡中存在，并且前者占优势。烯丙氧基碳正离子参与最终的重排步骤，并决定反应的区域选择性。此外，2,3-不饱和吡喃糖环的构象稳定性决定了反应的立体选择性。确定了影响这种稳定性的因素，以及能够识别 H 和 H 构象的 NMR 数据。2,3-不饱和薯蓣皂苷的选择性氢化提供了一系列 2,3-二脱氧类似物。本文介绍了合成皂苷的抗癌、溶血和抗菌活性，并讨论了结构-活性关系。
