Direct Experimental Characterization of a Sialyl Cation
Sialic acids are monosaccharide residues involved in several biological processes. Controlling the stereoselectivity of sialylation reactions is challenging and mechanistic studies on the structure of its intermediate, the sialyl cation, are scarce. Here it is shown that a sialyl cation can be generated and isolated from an ionized sialic acid precursor. This short-lived species is structurally characterized for the first time using cryogenic infrared spectroscopy. In combination with quantum chemical calculations, the results reveal that the positive charge at the anomeric carbon of the sialyl cation is stabilized by remote participation of the C5-NHAc group leading to the formation of a bridged structure. In this structure, the β-side is shielded from nucleophilic attack, potentially explaining the α-selectivity of this building block in S<sub>N</sub>1-type sialylation reactions. Other modes of participation are energetically unfavored and cannot be observed experimentally.
Authors
- Kevin Pagel (ORCID: https://orcid.org/0000-0001-8054-4718)
- Kim Greis (ORCID: https://orcid.org/0000-0002-9107-2282)
- Mark W. Peczuh (ORCID: https://orcid.org/0000-0002-3028-6551)
- Caleb E. Griesbach (ORCID: https://orcid.org/0000-0002-6969-4851)
- Gert von Helden (ORCID: https://orcid.org/0000-0001-7611-8740)
- América Y. Torres‐Boy (ORCID: https://orcid.org/0009-0002-8364-2668)
- Franziska Dahlmann (ORCID: https://orcid.org/0000-0003-2898-7460)
Institutions
- University of Connecticut (US)
- University of Toronto (CA)
- Universität Innsbruck (AT)
- Board of the Swiss Federal Institutes of Technology (CH)
- Fritz Haber Institute of the Max Planck Society (DE)
- Yale University (US)
- ETH Zurich (CH)
- Freie Universität Berlin (DE)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1002/chem.202403724
- Citations
- 5
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.25
Funders
- National Science Foundation
- Fulbright Association
- Stiftelsen för Strategisk Forskning
- Fonds National de la Recherche Luxembourg
- Austrian Science Fund
- Air Force Office of Scientific Research
- H2020 European Research Council