Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative
The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-me...
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sg-ntu-dr.10356-1805832024-10-18T15:32:11Z Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative Zhao, Xiaoya Ding, Han Guo, Aoxin Zhong, Xuemei Zhou, Siai Wang, Guoqing Liu, Yuhua Ishiwata, Akihiro Tanaka, Katsunori Cai, Hui Liu, Xue-Wei Ding, Feiqing School of Chemistry, Chemical Engineering and Biotechnology Chemistry Capsular polysaccharide Vaccine development The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-mediated 1,2-cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6-O-tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : β = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2-cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1GlcN-iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an SN1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI2-activated acceptor complex under the influence of the 2-azido gauche effect. Published version This study was supported partly by the Shenzhen Science and Technology Program (No. GJHZ20220913142602004 to F. D.), the Guangdong Basic and Applied Basic Research Funding (No. 2024A1515010015 to F. D.). 2024-10-14T02:49:47Z 2024-10-14T02:49:47Z 2024 Journal Article Zhao, X., Ding, H., Guo, A., Zhong, X., Zhou, S., Wang, G., Liu, Y., Ishiwata, A., Tanaka, K., Cai, H., Liu, X. & Ding, F. (2024). Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative. Chemical Science, 15(32), 12889-12899. https://dx.doi.org/10.1039/d4sc03449j 2041-6520 https://hdl.handle.net/10356/180583 10.1039/d4sc03449j 39148796 2-s2.0-85199064332 32 15 12889 12899 en Chemical Science © 2024 The Author(s). Published by the Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. application/pdf |
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Chemistry Capsular polysaccharide Vaccine development Zhao, Xiaoya Ding, Han Guo, Aoxin Zhong, Xuemei Zhou, Siai Wang, Guoqing Liu, Yuhua Ishiwata, Akihiro Tanaka, Katsunori Cai, Hui Liu, Xue-Wei Ding, Feiqing Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
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The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-mediated 1,2-cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6-O-tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : β = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2-cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1GlcN-iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an SN1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI2-activated acceptor complex under the influence of the 2-azido gauche effect. |
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School of Chemistry, Chemical Engineering and Biotechnology |
author_facet |
School of Chemistry, Chemical Engineering and Biotechnology Zhao, Xiaoya Ding, Han Guo, Aoxin Zhong, Xuemei Zhou, Siai Wang, Guoqing Liu, Yuhua Ishiwata, Akihiro Tanaka, Katsunori Cai, Hui Liu, Xue-Wei Ding, Feiqing |
format |
Article |
author |
Zhao, Xiaoya Ding, Han Guo, Aoxin Zhong, Xuemei Zhou, Siai Wang, Guoqing Liu, Yuhua Ishiwata, Akihiro Tanaka, Katsunori Cai, Hui Liu, Xue-Wei Ding, Feiqing |
author_sort |
Zhao, Xiaoya |
title |
Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
title_short |
Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
title_full |
Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
title_fullStr |
Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
title_full_unstemmed |
Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative |
title_sort |
zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of acinetobacter baumannii k48 capsular pentasaccharide derivative |
publishDate |
2024 |
url |
https://hdl.handle.net/10356/180583 |
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1814777744115892224 |