Hydrogen-Bonding-Assisted Exogenous Nucleophilic Reagent Effect for beta-Selective Glycosylation of Rare 3-Amino Sugars
Hydrogen-Bonding-Assisted Exogenous Nucleophilic Reagent Effect for beta-Selective Glycosylation of Rare 3-Amino Sugars
复制标题
氢键辅助外源亲核试剂对稀有 3-氨基糖 β-选择性糖基化的影响
DOI：
10.1021/jacs.9b01862
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发表时间：
2019
影响因子：
15
通讯作者：
Wan Qian
中科院分区：
文献类型：
--
作者：
Zeng Jing;Wang Ruobin;Zhang Shuxin;Fang Jing;Liu Shanshan;Sun Guangfei;Xu Bingbing;Xiao Ying;Fu Dengxian;Zhang Wenqi;Hu Yixin;Wan Qian
脱氧糖的立体选择性糖基化的挑战在碳水化合物化学中是众所周知的。我们在此报告了一种构建较少研究的 3,5-反式-3-氨基-2,3,6-三脱氧糖（3,5-反式-3-ADS）β-糖苷键的新策略，该糖苷键构成了几种生物学上重要的抗生素的核心结构。目前的方案利用 3,5-trans-3-ADS 中的 C-3 轴向磺酰胺基团作为氢键 (H-bond) 供体，并将亚化学计量的氧化膦重新用作外源亲核试剂 (exNu)，以在前者和衍生的 α-氧鏻离子之间建立分子内 H-键。这种关键的相互作用稳定了α-面覆盖的中间体，以抑制更具反应性的β-中间体的形成，从而产生反向的β-选择性，这对于exNu介导的糖基化系统来说是非常规的。可适应多种底物，并且这种氢键辅助的 exNu 效应确保了良好至优异的 β-选择性。对含有 3,5-trans-3-ADS 的天然产物和药物的结构修饰以及亲和素红霉素中三糖单元的合成进一步证明了当前策略的稳健性。
Challenges for stereoselective glycosylation of deoxy sugars are notorious in carbohydrate chemistry. We herein report a novel strategy for the construction of the less investigated β-glycosidic bonds of 3,5-trans-3-amino-2,3,6-trideoxy sugars (3,5-trans-3-ADSs), which constitute the core structure of several biologically important antibiotics. Current protocol leverages a C-3 axial sulfonamide group in 3,5-trans-3-ADSs as a hydrogen-bond (H-bond) donor and repurposes substoichiometric phosphine oxide as an exogenous nucleophilic reagent (exNu) to establish an intramolecular H-bond between the former and the derived α-oxyphosphonium ion. This pivotal interaction stabilizes the α-face-covered intermediate to inhibit the formation of the more reactive β-intermediate, thereby yielding reversed β-selectivity, which is unconventional for an exNu-mediated glycosylation system. A wide range of substrates was accommodated, and good to excellent β-selectivities were ensured by this H-bonding-assisted exNu effect. The robustness of the current strategy was further attested by the architectural modification of natural products and drugs containing 3,5-trans-3-ADSs, as well as the synthesis of a trisaccharide unit in avidinorubicin.