Kinetics of enzyme-catalysed de-symmetrisation of prochiral substrates : product enantiomeric excess is not always constant

Halling, Peter J (2021) Kinetics of enzyme-catalysed de-symmetrisation of prochiral substrates : product enantiomeric excess is not always constant. Beilstein Journal of Organic Chemistry, 17. pp. 873-884. ISSN 1860-5397 (https://doi.org/10.3762/bjoc.17.73)

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Abstract

The kinetics of enzymatic desymmetrisation were analysed for the most common kinetic mechanisms: ternary complex ordered (prochiral ketone reduction); ping-pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the reaction proceeds to high conversion. For example, an ee of 0.95 at the start of the reaction can decline to less than 0.5 at 95% of equilibrium conversion, but for different enzyme properties it will remain almost unchanged. For most mechanisms a single function of multiple enzyme rate constants (which can be termed ee decline parameter, eeDP) accounts for the major effect on the tendency for the ee to decline. For some mechanisms, the concentrations or ratios of the starting materials have an important influence on the fall in ee. For the application of enzymatic desymmetrisation it is important to study if and how the product ee declines at high conversion.

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