Acid-catalyzed hydrolysis of 5-enolpyruvylshikimate 3-phosphate (EPSP) and some simple models of its vinyl ether functional group

Article abstract of DOI:10.1021/ja00033a039

Rates of hydrolysis of the vinyl ether functional groups of 5-enolpyruvylshikimate 3-phosphate (EPSP), α-methoxyacrylic acid, and methyl α-methoxyacrylate were measured in concentrated and dilute mineral acid solutions and carboxylic acid buffers, and rate profiles were constructed from the data so obtained. The results for methyl α-methoxyacrylate show a monotonic decrease in reaction rate with decreasing solvent acidity, culminating in a first-order dependence on [H⁺] in dilute acids; this and solvent isotope effects on this reaction indicate that this process occurs by the conventional mechanism for vinyl ether hydrolysis involving rate-determining proton transfer from hydronium ion to the substrate. The rate profiles for EPSP and α-methoxyacrylic acid are similar to that of methyl α-methoxyacrylate in concentrated acids, but they show uncatalyzed plateaus in the region pC_H+ = 1-3 that then give way to renewed acid catalysis beyond pC_H = 4. Solvent isotope effects suggest that these plateaus represent reaction via ionization of the carboxylic acid groups of these substrates followed by conventional hydrolysis of the vinyl ether groups of the carboxylate ions. Analysis of the data gives pK_a = 3.77 for EPSP and pK_a = 3.46 for α-methoxyacrylic acid and provides rate constants which show rate-retarding substituent effects on vinyl ether hydrolysis of 16 for α-CO₂^-, 20 000 for α-CO₂H, and 81 000 for α-CO₂Me.