Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
Nat Commun. 2020 May 15;11(1):2431. doi: 10.1038/s41467-020-16365-8.
Chemical desymmetrization reactions of meso-diols are highly effective for the precise and efficient synthesis of chiral molecules. However, even though enzyme-catalyzed desymmetric glycosylations are frequently found in nature, there is no method for highly diastereoselective desymmetric chemical glycosylation of meso-diols. Herein, we report a highly diastereoselective desymmetric 1,2-cis-glycosylation of meso-diols found in myo-inositol 1,3,5-orthoesters using a boronic acid catalyst based on predictions of regioselectivity by density functional theory (DFT) calculations. The enantiotopic hydroxyl groups of the meso-diols are clearly differentiated by the stereochemistry at the C2 position of the glycosyl donor with excellent regioselectivities. In addition, the present method is successfully applied to the synthesis of core structures of phosphatidylinositolmannosides (PIMs) and glycosylphosphatidylinositol (GPI) anchors, and common β-mannoside structures of the LLBM-782 series of antibiotics.
手性分子的精准、高效合成中，meso-二醇的化学不对称反应是非常有效的。然而，尽管酶催化的不对称糖基化在自然界中经常被发现，但目前还没有高效的非对映选择性手性 meso-二醇的不对称化学糖苷化方法。在此，我们报道了一种基于密度泛函理论（DFT）计算的区域选择性预测的硼酸催化剂，对肌醇 1,3,5-邻苯二甲酸酯中的 meso-二醇进行高度非对映选择性的 1,2-顺式糖苷化。糖苷供体的 C2 位的立体化学明显区分了 meso-二醇的不等位羟基，具有极好的区域选择性。此外，本方法成功应用于磷脂酰肌醇甘露糖苷（PIMs）和糖基磷脂酰肌醇（GPI）锚的核心结构以及抗生素 LLBM-782 系列的常见β-甘露糖苷结构的合成。
