β-Mannosylation via O-Alkylation of Anomeric Cesium Alkoxides: Mechanistic Studies and Synthesis of the Hexasaccharide Core of Complex Fucosylated N-Linked Glycans,European Journal of Organic Chemistry

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β-Mannosylation via O-Alkylation of Anomeric Cesium Alkoxides: Mechanistic Studies and Synthesis of the Hexasaccharide Core of Complex Fucosylated N-Linked Glycans
European Journal of Organic Chemistry ( IF 2.5 ) Pub Date : 2020-04-02 , DOI: 10.1002/ejoc.202000313
Shuai Meng ₁ , Bishwa Raj Bhetuwal ₁ , Hai Nguyen ₁ , Xiaotian Qi ₂ , Cheng Fang ₂ , Kevin Saybolt ₃ , Xiaohua Li ₃ , Peng Liu _{2,

4} , Jianglong Zhu ₁

Affiliation

A number of structurally diverse D-mannose-derived lactols, including various deoxy-D-mannoses and conformationally restricted bicyclic D-mannoses, have been synthesized and investigated in mechanistic studies of β-mannosylation via Cs2CO3-mediated anomeric O-alkylation. It was found that deoxy mannoses or conformationally restricted bicyclic D-mannoses are not as reactive as their corresponding parent mannose. This type of β-mannosylation proceeds efficiently when the C2-OH is left free, and protection of that leads to inferior results. NMR studies of D-mannose-derived anomeric cesium alkoxides indicated the predominance of the equatorial β-anomer after deprotonation. Reaction progress kinetic analysis suggested that monomeric cesium alkoxides be the key reactive species for alkylation with electrophiles. DFT calculations supported that oxygen atoms at C2, C3, and C6 of mannose promote the deprotonation of the anomeric hydroxyl group by Cs2CO3 and chelating interactions between Cs and these oxygen atoms favour the formation of equatorial anomeric alkoxides, leading to the highly β-selective anomeric O-alkylation. Based on experimental data and computational results, a revised mechanism for this β-mannosylation is proposed. The utilization of this β-mannosylation was demonstrated by an efficient synthesis of the hexasaccharide core of complex fucosylated N-linked glycans.

中文翻译：

通过异头铯醇盐的 O-烷基化进行 β-甘露糖基化：复杂岩藻糖基化 N-连接聚糖的六糖核心的机理研究和合成

已经合成了许多结构多样的 D-甘露糖衍生的乳醇，包括各种脱氧-D-甘露糖和构象限制的双环 D-甘露糖，并通过 Cs2CO3 介导的异头 O-烷基化进行 β-甘露糖基化的机理研究。研究发现，脱氧甘露糖或构象限制的双环D-甘露糖的反应性不如其相应的母体甘露糖。当 C2-OH 游离时，这种类型的 β-甘露糖基化会有效进行，而对其进行保护会导致较差的结果。 D-甘露糖衍生的异头铯醇盐的 NMR 研究表明去质子化后赤道 β-异头占主导地位。反应进程动力学分析表明单体铯醇盐是亲电子试剂烷基化的关键反应物种。 DFT计算支持甘露糖C2、C3和C6上的氧原子促进Cs2CO3对异头羟基的去质子化，并且Cs和这些氧原子之间的螯合相互作用有利于形成赤道异头醇盐，从而导致高度β-选择性异头O-烷基化。基于实验数据和计算结果，提出了这种β-甘露糖基化的修正机制。通过复杂岩藻糖基化 N-连接聚糖的六糖核心的有效合成证明了这种 β-甘露糖基化的利用。

更新日期：2020-04-02

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