A method is presented for predicting the reactivity of alcoholic aglycons in the -glucosidase mediated glucosylation reaction. The successful enzymatic glucosylation of an aglycon appears to be mainly dependent on the nucleophilicity of the aglycon. Vinylic and phenolic aglycons are not nucleophilic enough to be glucosylated enzymatically, although their chemical glucosylation is facile. By using PM3 and AM1 semi-empirical methods, the magnitude of this nucleophilicity can be calculated and was found to correlate with the charge on the reacting atom of the aglycon. Based on this trend, the aglycons can be classified as reacting or non-reacting. The orbital related parameters seem to have a limited influence on the reaction behaviour. In addition to these calculations, the energy of the transition state of two enzymatic reactions has been calculated using a simplified model of the enzyme active site for both an experimentally reacting and an experimentally non-reacting aglycon (cyclohexanol and phenol, respectively). The activation energy for the cyclohexanol complex was computed to be 1.3 kcal mol-1, while the calculated activation energy for the phenol complex is 15.8 kcal mol-1. This difference can indeed explain the fact that cyclohexanol is easily glucosylated while phenol is not.
|Journal||Journal of Chemical Society, Perkin Transactions|
|Publication status||Published - 2000|