Hydrolyses of Ketosides

1 Hydrolysis of Sialic Acid (Neuraminic Acid) Derivatives 

Aryl N-acetyl a-neuraminides (a-NeuNAcOAr)(natural stereochemistry) 

Both a- and p-NeuNAcOPNP hydrolyse through four processes the spontaneous departure of the phenolate from the substrate anion, an acid-catalysed process of the neutral molecule, a base-catalysed process of the anion and an apparently spontaneous process of the neutral molecule. This last process was shown to be the kinetically equivalent acid-catalysed hydrolysis of the anion of p-NeuNAcOAr by a jSig value of 0.14, and of the anion of a-NeuNAcOAr by a jSig value of 0.00 and a solvent deuterium kinetic isotope effect of 0.96, when any intramolecular general acid catalysis would give rise to negative jSig values and direct solvent isotope effects. 

The measurement of individual proS and proR p-deuterium effects for a-NeuNAcOPNP, and also the inductive effect of deuterium substitution at position 4, enabled eqn (3.12) to be solved for the acid-catalysed hydrolysis of the neutral molecule, the acid-catalysed hydrolysis of the anion and the spontaneous reaction. An isotope effect kn/ko of 1.000 for the proS and position 4 hydrons for the spontaneous and acid-catalysed reactions of the anion indicated the inductive correction in eqn (3.12) was zero. TheproR effects of 1.075 and l.OSg then lead immediately to a value of the proR hydron breaking C-O bond dihedral angle (6) of 30° and values of (kH/kD)max of 1.09g and 1.115 for the spontaneous and acid-catalysed processes of the anion, respectively. The acid-catalysed hydrolysis of neutral a-NeuNAcOPNP, by contrast, has a proS effect of 1.02s and a proR effect of 1.06g, indicating a less flattened transition state in which 6 30°, The value of 0.97g for the effect at C4 is too high to be wholly inductive [implausible values of (kH/kD)max result if ln(kH/kD)i is set equal to 31n0.976], but even in the absence of any inductive correction a (kH/kD)max of 1.19 results, indicating a much more electron-deficient reaction centre. 

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