Some Recent Developments Regarding the Mechanism of Glycoside Hydrolysis

4 Some Recent Developments Regarding the Mechanism of Glycoside Hydrolysis 

In 1980, van Eikeren [45] undertook a study of acid-catalyzed hydrolysis of conformationally rigid methyl acetals 61 and 62 (Fig. 3.16), arguing that the rates of anomer hydrolysis may be affected by the conformation of a glycoside. 

From the composition of the equilibrium mixture obtained after the acid-catalyzed equilibration of 61 and 62 (68 1 % of axial 61 and 32 1 % of equatorial 62 anomer), it was calculated that the axial a-anomer 61a is more stable than p-anomer 62(1 by 0.45 kcal/mol which was in full agreement with the concept of the anomeric effect. On the other hand, in contrast to the results for alkyl glycosides, a comparison of the second-order rate constants showed that the axial anomer hydrolyzes 1.51 0.22 times faster than the equatorial anomer, indicating that the TS energy of the transition state in the hydrolysis of 61 is lower by 0.25 kcal/mol than the TS energy of the transition state in the hydrolysis of 62. Thus, the difference in energy between the TS of 61a and 62 is 0.7 kcal/mol (Fig. 3.17). 

The acid-catalyzed hydrolyses of the axial and equatorial anomers 61 and 62 were studied in aqueous HCI/acetone solvent mixtures maintained at constant temperature in a water bath. The dependence of on acid concentration and temperature was measured because the conclusions are justified mily if the anomers show similar variations in rate with changes in the catalyzing acid and temperature. 

The examination of activation parameters for the hydrolysis of 61 and 62 (Table 3.9) shows that both anomers exhibit positive enthalpies and entropies of activation as what would be expected for a dissociative mechanism. The observation that the axial anomer exhibits both a larger positive enthalpy and entropy of activation than the equatorial anomer suggests that the rate-determining transition state of the axial anomer involves more extensive C-O bond cleavage. 

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