四川大学钮大文团队报道了钯催化实现苯酚的交叉偶联类SN2糖基化。相关研究成果于2023年11月24日发表于《科学》期刊。

尽管立体糖苷在生命和材料科学中很重要，但其有效构建仍然是一个挑战。如果糖基化方法像钯（Pd）催化的交叉偶联一样可靠和模块化，那么碳水化合物功能的研究将取得进展。然而，Pd催化在形成sp2杂化的碳中心方面表现出色，而糖基化主要建立sp3杂化的C–O键。

该文中，研究人员报道了一种糖基化平台，通过钯催化的SN2从苯酚转移到稳定的含芳基碘化物的糖基硫化物。关键的Pd（II）氧化加成中间体从芳基化试剂（Csp2亲电试剂）分化为糖基化试剂。该方法继承了交叉耦合反应的许多优点，包括操作简单和官能团耐受。它保留了各种底物的SN2机制，并适用于商业药物和天然产物的后期糖基化。

附：英文原文

Title: Palladium catalysis enables cross-coupling–like SN2-glycosylation of phenols

Author: Li-Fan Deng, Yingwei Wang, Shiyang Xu, Ao Shen, Hangping Zhu, Siyu Zhang, Xia Zhang, Dawen Niu

Issue&Volume: 2023-11-24

Abstract: Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies of carbohydrate functions would be advanced if glycosylation methods were as reliable and modular as palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels in forming sp2-hybridized carbon centers whereas glycosylation mostly builds sp3-hybridized C–O linkages. We report a glycosylation platform through Pd-catalyzed SN2 displacement from phenols toward bench-stable, aryl-iodide–containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges from an arylating agent (Csp2 electrophile) to a glycosylating agent (Csp3 electrophile). This method inherits many merits of cross-coupling reactions, including operational simplicity and functional group tolerance. It preserves the SN2 mechanism for various substrates and is amenable to late-stage glycosylation of commercial drugs and natural products.

DOI: adk1111

Source: https://www.science.org/doi/10.1126/science.adk1111