Chang Chun-Wei, Lin Mei-Huei, Chiang Tsun-Yi, Wu Chia-Hui, Lin Tzu-Chun, Wang Cheng-Chung
Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program (TIGP), Academia Sinica, Taipei 115, Taiwan.
Sci Adv. 2023 Oct 20;9(42):eadk0531. doi: 10.1126/sciadv.adk0531. Epub 2023 Oct 18.
The stereoselectivity of glycosidic bond formation continues to pose a noteworthy hurdle in synthesizing carbohydrates, primarily due to the simultaneous occurrence of S1 and S2 processes during the glycosylation reaction. Here, we applied an in-depth analysis of the glycosylation mechanism by using low-temperature nuclear magnetic resonance and statistical approaches. A pathway driven by counterion exchanges and reaction byproducts was first discovered to outline the stereocontributions of intermediates. Moreover, the relative reactivity values, acceptor nucleophilic constants, and Hammett substituent constants (σ values) provided a general index to indicate the mechanistic pathways. These results could allow building block tailoring and reaction condition optimization in carbohydrate synthesis to be greatly facilitated and simplified.
糖苷键形成的立体选择性仍然是碳水化合物合成中一个值得注意的障碍，主要是因为在糖基化反应过程中S1和S2过程同时发生。在这里，我们通过使用低温核磁共振和统计方法对糖基化机制进行了深入分析。首先发现了一条由抗衡离子交换和反应副产物驱动的途径，以概述中间体的立体贡献。此外，相对反应活性值、受体亲核常数和哈米特取代基常数（σ值）提供了一个通用指标来指示反应机理途径。这些结果可以极大地促进和简化碳水化合物合成中构建模块的定制和反应条件的优化。
