Stereoselective chemical N-glycoconjugation of amines via CO<sub>2</sub> incorporation.

Peng, Zihan; Xiao, Qian; Xia, Yan; Xia, Mingyu; Yu, Jia; Fang, Pengfei; Tang, Yu; Yu, Biao · Nat Commun · 2024

basic_science · Level V

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Abstract

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<sub>2</sub> atmosphere and a subsequent S<sub>N</sub>2 type reaction with glycosyl halides. This work provides an example of using CO<sub>2</sub> 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.