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Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions

[Image: see text] Carbohydrates (glycans, saccharides, and sugars) are essential molecules in all domains of life. Research on glycoscience spans from chemistry to biomedicine, including material science and biotechnology. Access to pure and well-defined complex glycans using synthetic methods depen...

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Autores principales: Franconetti, Antonio, Ardá, Ana, Asensio, Juan Luis, Blériot, Yves, Thibaudeau, Sébastien, Jiménez-Barbero, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173606/
https://www.ncbi.nlm.nih.gov/pubmed/33930267
http://dx.doi.org/10.1021/acs.accounts.1c00021
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author Franconetti, Antonio
Ardá, Ana
Asensio, Juan Luis
Blériot, Yves
Thibaudeau, Sébastien
Jiménez-Barbero, Jesús
author_facet Franconetti, Antonio
Ardá, Ana
Asensio, Juan Luis
Blériot, Yves
Thibaudeau, Sébastien
Jiménez-Barbero, Jesús
author_sort Franconetti, Antonio
collection PubMed
description [Image: see text] Carbohydrates (glycans, saccharides, and sugars) are essential molecules in all domains of life. Research on glycoscience spans from chemistry to biomedicine, including material science and biotechnology. Access to pure and well-defined complex glycans using synthetic methods depends on the success of the employed glycosylation reaction. In most cases, the mechanism of the glycosylation reaction is believed to involve the oxocarbenium ion. Understanding the structure, conformation, reactivity, and interactions of this glycosyl cation is essential to predict the outcome of the reaction. In this Account, building on our contributions on this topic, we discuss the theoretical and experimental approaches that have been employed to decipher the key features of glycosyl cations, from their structures to their interactions and reactivity. We also highlight that, from a chemical perspective, the glycosylation reaction can be described as a continuum, from unimolecular S(N)1 with naked oxocarbenium cations as intermediates to bimolecular S(N)2-type mechanisms, which involve the key role of counterions and donors. All these factors should be considered and are discussed herein. The importance of dissociative mechanisms (involving contact ion pairs, solvent-separated ion pairs, solvent-equilibrated ion pairs) with bimolecular features in most reactions is also highlighted. The role of theoretical calculations to predict the conformation, dynamics, and reactivity of the oxocarbenium ion is also discussed, highlighting the advances in this field that now allow access to the conformational preferences of a variety of oxocarbenium ions and their reactivities under S(N)1-like conditions. Specifically, the ground-breaking use of superacids to generate these cations is emphasized, since it has permitted characterization of the structure and conformation of a variety of glycosyl oxocarbenium ions in superacid solution by NMR spectroscopy. We also pay special attention to the reactivity of these glycosyl ions, which depends on the conditions, including the counterions, the possible intra- or intermolecular participation of functional groups that may stabilize the cation and the chemical nature of the acceptor, either weak or strong nucleophile. We discuss recent investigations from different experimental perspectives, which identified the involved ionic intermediates, estimating their lifetimes and reactivities and studying their interactions with other molecules. In this context, we also emphasize the relationship between the chemical methods that can be employed to modulate the sensitivity of glycosyl cations and the way in which glycosyl modifying enzymes (glycosyl hydrolases and transferases) build and cleave glycosidic linkages in nature. This comparison provides inspiration on the use of molecules that regulate the stability and reactivity of glycosyl cations.
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spelling pubmed-81736062021-06-04 Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions Franconetti, Antonio Ardá, Ana Asensio, Juan Luis Blériot, Yves Thibaudeau, Sébastien Jiménez-Barbero, Jesús Acc Chem Res [Image: see text] Carbohydrates (glycans, saccharides, and sugars) are essential molecules in all domains of life. Research on glycoscience spans from chemistry to biomedicine, including material science and biotechnology. Access to pure and well-defined complex glycans using synthetic methods depends on the success of the employed glycosylation reaction. In most cases, the mechanism of the glycosylation reaction is believed to involve the oxocarbenium ion. Understanding the structure, conformation, reactivity, and interactions of this glycosyl cation is essential to predict the outcome of the reaction. In this Account, building on our contributions on this topic, we discuss the theoretical and experimental approaches that have been employed to decipher the key features of glycosyl cations, from their structures to their interactions and reactivity. We also highlight that, from a chemical perspective, the glycosylation reaction can be described as a continuum, from unimolecular S(N)1 with naked oxocarbenium cations as intermediates to bimolecular S(N)2-type mechanisms, which involve the key role of counterions and donors. All these factors should be considered and are discussed herein. The importance of dissociative mechanisms (involving contact ion pairs, solvent-separated ion pairs, solvent-equilibrated ion pairs) with bimolecular features in most reactions is also highlighted. The role of theoretical calculations to predict the conformation, dynamics, and reactivity of the oxocarbenium ion is also discussed, highlighting the advances in this field that now allow access to the conformational preferences of a variety of oxocarbenium ions and their reactivities under S(N)1-like conditions. Specifically, the ground-breaking use of superacids to generate these cations is emphasized, since it has permitted characterization of the structure and conformation of a variety of glycosyl oxocarbenium ions in superacid solution by NMR spectroscopy. We also pay special attention to the reactivity of these glycosyl ions, which depends on the conditions, including the counterions, the possible intra- or intermolecular participation of functional groups that may stabilize the cation and the chemical nature of the acceptor, either weak or strong nucleophile. We discuss recent investigations from different experimental perspectives, which identified the involved ionic intermediates, estimating their lifetimes and reactivities and studying their interactions with other molecules. In this context, we also emphasize the relationship between the chemical methods that can be employed to modulate the sensitivity of glycosyl cations and the way in which glycosyl modifying enzymes (glycosyl hydrolases and transferases) build and cleave glycosidic linkages in nature. This comparison provides inspiration on the use of molecules that regulate the stability and reactivity of glycosyl cations. American Chemical Society 2021-04-30 2021-06-01 /pmc/articles/PMC8173606/ /pubmed/33930267 http://dx.doi.org/10.1021/acs.accounts.1c00021 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Franconetti, Antonio
Ardá, Ana
Asensio, Juan Luis
Blériot, Yves
Thibaudeau, Sébastien
Jiménez-Barbero, Jesús
Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title_full Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title_fullStr Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title_full_unstemmed Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title_short Glycosyl Oxocarbenium Ions: Structure, Conformation, Reactivity, and Interactions
title_sort glycosyl oxocarbenium ions: structure, conformation, reactivity, and interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173606/
https://www.ncbi.nlm.nih.gov/pubmed/33930267
http://dx.doi.org/10.1021/acs.accounts.1c00021
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