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Updated: Jan 26, 2026

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
Published on: September 6, 2019
The one-pot nonhydrolysis Staudinger reaction and Staudinger or SPAAC ligation
Longhuai Cheng1, Xueying Kang, Dan Wang
1State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, National Engineering Research Center of Pesticide (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, China. zhenxi@nankai.edu.cn.
Abstract:
The combined usage of two bioorthogonal reactions can provide hetero-bifunctional molecules under physiological conditions for various applications. Based on the Nonhydrolysis Staudinger Reaction (NSR), we design and develop a bisazido linker 1 for chemoselective dual-functionalization without the need of protection using catalyst-free and one-pot procedures. The NSR is much faster with tetrafluorinated aromatic azide than that the Staudinger-Bertozzi or SPAAC ligation with alkyl azide, as revealed by HPLC analysis and fluorescence kinetics. Based on the tandem NSR and Staudinger-Bertozzi ligation, we prepare a molecular beacon 7 from 1 in one-pot synthesis with a recovery yield of 32%. When a faster SPAAC ligation is used instead of the Staudinger-Bertozzi ligation, compound 8 is prepared in the tandem NSR and SPAAC reactions with a recovery yield of 59%. As a proof-of-concept study, the tandem NSR and SPAAC ligation is further used to produce a FRET-based dyad in living cells, as revealed by dual-color bioimaging. This work shows that NSR can be combined with other bioorthogonal reactions without the need of protection in one-pot.
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