The N-Acetyl Neuraminyl Oxecarbenium Ion Is an Intermediate in the Presence of Anionic Nucleophiles

Solvolysis of CMP N-acetyl neuraminate (CMP-NeuAc) in 1.8 M acetate buffer at pH 5 containing 0.9 M azide results in the formation of both anomers of 2-deoxy-2-azido N-acetyl neuraminic acid in addition to N-acetyl neuraminic acid as determined by 1H-NMR product analysis. A rate dependence on [azide] was observed with an apparent bimolecular rate constant of (2.1 ± 0.3) × 10-3 M-l min-l which could only account for half of the azido-NeuAc formed. Comparison of rate, product ratio, and stereochemical data indicate that concurrent pathways for formation of N3-NeuAc are operative, with 17% of product forming from reaction of azide and the tight ion pair, 12% via the solvent separated ion pair, and 6% from the free NeuAc oxocarbenium ion. From the corrected product ratio data, the lifetime of the oxocarbenium ion was estimated to be ≥3 × 10-11 s. Solvolysis of CMP-NeuAc at pL = 5.0 afforded an observed solvent deuterium isotope effect (SDIE) kH2O/kD2O = 0.45, consistent with specific acid catalysis of glycosi...