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Catching elusive glycosyl cations in a condensed phase with HF/SbF5 superacid

Nature Chemistry volume 8, pages 186–191 (2016)Cite this article

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Abstract

Glycosyl cations are universally accepted key ionic intermediates in the mechanism of glycosylation, the reaction that covalently links carbohydrates to other molecules. These ions have remained hypothetical species so far because of their extremely short life in organic media as a consequence of their very high reactivity. Here, we report the use of liquid hydrofluoric acid–antimony pentafluoride (HF/SbF5) superacid to generate and stabilize the glycosyl cations derived from peracetylated 2-deoxy and 2-bromoglucopyranose in a condensed phase. Their persistence in this superacid medium allows their three-dimensional structure to be studied by NMR, aided by complementary computations. Their deuteration further confirms the impact of the structure of the glycosyl cation on the stereochemical outcome of its trapping.

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Figure 1: Prototype of the glycosylation mechanism and ionic species observed by NMR.
Figure 2: Generation and NMR spectra of 2-deoxyglucosyl oxocarbenium ion 6 in HF/SbF5 at −40 °C.
Figure 3: Conformational preferences of 2-deoxy- and 2-bromo-glucosyl oxocarbenium ions 6 and 7 in HF/SbF5 superacid.
Figure 4: Monitoring of the chemical stability of 2-deoxyglucosyl oxocarbenium ion 6 in HF/SbF5 by 1H-NMR.
Figure 5: Generation of 2-deoxy- and 2-bromo-glucosyl oxocarbenium ions 6 and 7 in HF/SbF5 followed by their trapping with methanol (40 equiv.) or cyclohexane-d12 (2 equiv.).

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Acknowledgements

A.M. acknowledges the Agence Nationale de la Recherche (ANR) for a PhD grant (project ANR-12-BS07-0003-01). N.P. acknowledges the Foundation for the Development of the Chemistry of Natural Products of the French Academy of Sciences for a post-doctoral fellowship. J.D., A.M.-M., S.T. and Y.B. acknowledge the French Centre National de la Recherche Scientifique, (PICS program), the ANR (project ANR-12-BS07-0003-01), the Regional Council Poitou-Charentes and the University of Poitiers for financial support. A.A. and J.J.-B. acknowledge the Centro de Supercomputación de Galicia (CESGA) for computational resources and the Ministery of Economy and Competitiveness of Spain for funding (project CTQ2012-32025).

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Authors and Affiliations

  1. Université de Poitiers, UMR-CNRS 7285, IC2MP, Equipe ‘Synthèse organique’, 4 rue Michel Brunet, TSA 51106, Poitiers Cedex 9, 86073, France

    A. Martin, J. Désiré, A. Martin-Mingot, N. Probst, S. Thibaudeau & Y. Blériot

  2. CIC bioGUNE, Parque Tecnológico de Bizkaia, Edif. 801A-1°, Derio-Bizkaia 48160, and Ikerbasque, Basque Foundation for Science, Maria López de Haro 3, 48013 Bilbao, Spain

    A. Arda & J. Jiménez-Barbero

  3. Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8232, IPCM, LabEx MiChem, F-75005 Paris, France

    P. Sinaÿ

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  1. A. Martin
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Contributions

Y.B. and P.S. initiated the study. Y.B. and S.T. designed the study. A.M., N.P. and J.D. synthesized the sugar precursors. A.M., A.M.M. and N.P. performed the superacid experiments. A.M., A.M.M., J.D., S.T., Y.B., J.J.-B. and A.A. analysed the NMR spectra. J.J.-B. and A.A. performed the computation. Y.B., J.J.B. and S.T. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to J. Jiménez-Barbero, S. Thibaudeau or Y. Blériot.

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Martin, A., Arda, A., Désiré, J. et al. Catching elusive glycosyl cations in a condensed phase with HF/SbF5 superacid. Nature Chem 8, 186–191 (2016). https://doi.org/10.1038/nchem.2399

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