The Glycosylation Mechanisms of 6,3-Uronic Acid Lactones
The Glycosylation Mechanisms of 6,3-Uronic Acid Lactones
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DOI：
10.1002/anie.201902507
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发表时间：
2019-06-24
影响因子：
16.6
通讯作者：
Boltje, Thomas J.
中科院分区：
文献类型：
--
作者：
Elferink, Hidde;Mensink, Rens A.;Boltje, Thomas J.
糖醛酸是在不同生物体的细胞膜上发现的多糖的重要成分。为了制备含糖醛酸的寡糖，可以使用糖醛酸6，3-内酯，因为它们显示出固定的构象和独特的反应性和立体选择性。在此，我们报告了一种基于C-4乙酰甘露糖醛酸6，3-内酯供体的高β-选择性和有效的甘露糖供体。糖基化的机制是建立使用的技术组合，包括红外离子光谱结合量子化学计算和变温核磁共振（VT NMR）光谱。通过改变活化方案和受体亲核性来测定这些中间体在糖基化中的作用。观察到的趋势类似于充分研究的4，6-亚苄基糖苷，并可用于指导下一代立体选择性糖基供体的开发。
Uronic acids are important constituents of polysaccharides found on the cell membranes of different organisms. To prepare uronic-acid-containing oligosaccharides, uronic acid 6,3-lactones can be employed as they display a fixed conformation and a unique reactivity and stereoselectivity. Herein, we report a highly beta-selective and efficient mannosyl donor based on C-4 acetyl mannuronic acid 6,3-lactone donors. The mechanism of glycosylation is established using a combination of techniques, including infrared ion spectroscopy combined with quantum-chemical calculations and variable-temperature nuclear magnetic resonance (VT NMR) spectroscopy. The role of these intermediates in glycosylation is assayed by varying the activation protocol and acceptor nucleophilicity. The observed trends are analogous to the well-studied 4,6-benzylidene glycosides and may be used to guide the development of next-generation stereoselective glycosyl donors.