Peng Zihan, Xiao Qian, Xia Yan, Xia Mingyu, Yu Jia, Fang Pengfei, Tang Yu, Yu Biao
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.
Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Nat Commun. 2024 Nov 29;15(1):10373. doi: 10.1038/s41467-024-54523-4.
Chemical N-glycoconjugation can provide a unique way to tailor the properties of the ubiquitous amines for further expending their diverse functions and applications. Nevertheless, effective methodology for glycoconjugation of amines remains largely underdeveloped. Inspired by a biotransformation pathway of amine-containing drugs in vivo, we have developed an effective protocol that enables one-step chemical N-glycoconjugation of amines in high stereoselectivity under mild conditions. This protocol involves conversion of the amine moiety into the corresponding carbamate anion under CO atmosphere and a subsequent S2 type reaction with glycosyl halides. This work provides an example of using CO as the coupling unit in chemical glycoconjugation reactions. A case study on the resulting N-glycoconjugates of Crizotinib, an anticancer drug, demonstrates a quick cleavage of the glucosyl carbamate linkage, testifying that this N-glyconjugation method could serve as a general approach to procure novel prodrugs.
化学N-糖缀合可为定制无处不在的胺类的性质提供一种独特方法，以进一步拓展其多样的功能和应用。然而，用于胺类糖缀合的有效方法在很大程度上仍未得到充分发展。受体内含胺药物生物转化途径的启发，我们开发了一种有效方案，该方案能够在温和条件下以高立体选择性实现胺类的一步化学N-糖缀合。该方案包括在CO气氛下将胺部分转化为相应的氨基甲酸酯阴离子，随后与糖基卤化物进行S2型反应。这项工作提供了一个在化学糖缀合反应中使用CO作为偶联单元的例子。对一种抗癌药物克唑替尼所得N-糖缀合物的案例研究表明，氨基葡萄糖氨基甲酸酯键可快速裂解，证明这种N-糖缀合方法可作为制备新型前药的通用方法。
