Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
J Org Chem. 2021 Mar 19;86(6):4763-4778. doi: 10.1021/acs.joc.1c00151. Epub 2021 Mar 9.
Glycosidation plays a pivotal role in the synthesis of -glycosides and nucleosides that mediate a diverse range of biological processes. However, efficient glycosidation approach for the synthesis of both -glycosides and nucleosides remains challenging in terms of glycosidation yields, mild reaction conditions, readily available glycosyl donors, and cheap promoters. Here, we report a versatile -iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf)-promoted glycosidation approach with glycosyl -hexynylbenzoates as donors for the highly efficient synthesis of -glycosides and nucleosides. The glycosidation approach highlights the merits of mild reaction conditions, cheap promoters, extremely wide substrate scope, and good to excellent yields. Notably, the glycosidation approach performs very well in the construction of a series of challenging - and -glycosidic linkages. The glycosidation approach is then applied to the efficient synthesis of oligosaccharides via the one-pot strategy and the stepwise strategy. On the basis of the isolation and characterization of the departure species derived from the leaving group, a plausible mechanism of NIS/TMSOTf-promoted glycosidation of glycosyl -hexynylbenzoates is proposed.
糖基化在β-糖苷和核苷的合成中起着关键作用，这些化合物介导着广泛的生物过程。然而，从糖基化产率、温和的反应条件、易得的糖基供体和廉价的促进剂等方面来看，高效的β-糖苷和核苷的糖基化方法仍然具有挑战性。在这里，我们报道了一种多功能的β-碘代琥珀酰亚胺/三甲基硅基三氟甲磺酸酯（NIS/TMSOTf）促进的糖基化方法，以糖基-己炔基苯甲酸酯作为供体，高效合成β-糖苷和核苷。该糖基化方法的优点在于温和的反应条件、廉价的促进剂、极其广泛的底物范围和良好到优异的产率。值得注意的是，该糖基化方法在构建一系列具有挑战性的β-和β-糖苷键方面表现出色。该糖基化方法随后通过一锅法和分步法应用于寡糖的高效合成。基于离去基团衍生的离去物种的分离和表征，提出了 NIS/TMSOTf 促进糖基-己炔基苯甲酸酯糖基化的可能机制。
