Enzymes in organic synthesis. Influence of substrate structure on rates of horse liver alcohol dehydrogenase-catalysed oxidoreductions
Abstract
Detailed rate studies on horse liver alcohol dehydrogenase (HLADH)-catalysed oxidoreductions of a broad structural range of aliphatic alcohol and carbonyl substrates of organic chemical interest have been carried out in order to identify kinetic factors which remain significant in preparative-scale asymmetric synthetic applications of the enzyme. The data are consistent with an ordered Theorell–Chance mechanism for all the substrates examined. Coenzyme dissociation is largely rate-determining for primary alcohol and aldehyde oxidoreductions, but not for secondary alcohols or ketones. To a considerable extent hydrophobic binding of a substrate at the active site can be correlated with its relative reactivity. The preparative-scale implications of these results are discussed. One of the more important conclusions is that the degree of enantioselectivity achieable during HLADH-mediated transformations of racemates can be manipulated in some cases by varying the substrate concentration.