近日，美国麻省理工学院Wendlandt, Alison E.团队报道了动力学网络控制下GlcNAc选择性外聚化成GalNAc。2026年1月15日出版的《自然-化学》杂志发表了这项成果。

复杂反应网络能够达到由多个产物决定基元步骤产生的动力学项所共同控制的非平衡稳态。

研究组报道了一个四组分“方形”动力学网络的优化，该网络实现了N-乙酰氨基葡萄糖向N-乙酰氨基半乳糖的选择性光化学差向异构化。网络层面的机理研究揭示了反应条件变化如何通过网络中多个步骤的动力学调节实现高选择性。尽管缺乏分子细节层面的解析，这种网络尺度的分析精确指出了需要进一步探究的动力学控制关键连接点。

随后的分子层面机理研究表明，硼酸酯共催化剂的配位作用同时改变了氢原子攫取的位点选择性与氢原子捐赠的非对映选择性，从而协同促进N-乙酰氨基半乳糖而非其他异构体的生成。优化后的反应条件能够用于合成多种糖苷及聚糖类目标产物。这项工作进一步确立了动力学网络控制作为非平衡体系中实现选择性催化的通用范式。

附：英文原文

Title: Selective epimerization of GlcNAc to GalNAc through steady-state tuning under kinetic network control

Author: Zhang, Shuo, Occhialini, Gino, Carder, Hayden M., de Kleijne, Frank F. J., Wendlandt, Alison E.

Issue&Volume: 2026-01-15

Abstract: Complex reaction networks can reach out-of-equilibrium steady states governed by multiple kinetic terms arising from multiple product-determining elementary steps. Here we report the optimization of a four-component ‘square’ kinetic network that allows for selective photochemical epimerization of N-acetylglucosamine (GlcNAc) to N-acetylgalactosamine (GalNAc). Network-level mechanistic studies reveal how changes in reaction conditions lead to high selectivity through kinetic adjustments across multiple steps in the network. Although lacking in molecular detail, this network-scale analysis pinpoints kinetically controlling connections for further interrogation. Subsequent molecular-level mechanistic studies reveal that coordination by a boronic ester co-catalyst alters both the site selectivity of hydrogen-atom abstraction and the diastereoselectivity of hydrogen-atom donation, synergistically favouring the formation of GalNAc over other isomers. The optimal reaction conditions enable access to diverse glycosides and glycans of interest in carbohydrate synthesis. This work further establishes kinetic network control to be a versatile paradigm for selective catalysis in out-of-equilibrium systems.

DOI: 10.1038/s41557-025-02053-x

Source: https://www.nature.com/articles/s41557-025-02053-x