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_N1-type sialylation reactions. Other modes of participation are energetically unfavored and cannot be observed experimentally.