Maximise Equilibrium Conversion in Biphasic Catalysed Reactions: How to Obtain Reliable Data for Equilibrium Constants?

Abstract

For the prediction and optimisation of the equilibrium conversion in biphasic catalysed reactions, the equilibrium constant of the desired reaction and the partition coefficients of all reactants have to be known. Within this contribution we have examined the alcohol dehydrogenase-catalysed reduction of several linear and aromatic ketones in biphasic reaction media with respect to equilibrium conversion. In this example, the equilibrium constant can be expressed in terms of differences in oxidation-reduction potentials DE 0 . However, for a large variety of organic compounds, these data are quite rare in the literature. To overcome this lack of data, we have utilised methods of computational chemistry to calculate data for the Gibbs free energy DG R leading to the equilibrium constants of a homologous series of linear ketones. To obtain comparable data for the reduction of substituted acetophenone derivatives, the Hammett relation leads to the necessary equilibrium constants. Furthermore, we compare the equilibrium conversions of a set of cofactor regeneration methods for the alcohol dehydrogenase-catalysed reductions. These results lead to a time-saving experimental design for the enantioselective reduction of 2-octanone to (R)-2-octanol on a preparative scale utilising biphasic reaction conditions.

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

“…One of the reasons is that in the COSMOtherm calculations the cosolvent DMF could not be considered. However, in Figure 3-7 it becomes obvious that despite the fact that their absolute values are not predicted precisely, the overall trend is verified, which is in line with previous investigations (Eckstein et al, 2006b;Spiess et al, 2008a). In future studies more solvents should be tested in order to investigate the reliability of the COSMO-RS predictions.…”

“…However, this method can only predict thermodynamic properties at equilibrium, but no kinetic behavior. Moreover, COSMO-RS predicts general trends for partition coefficients, but no absolute values (Eckstein et al, 2006b;Spiess et al, 2008a).…”

Chemoenzymatic synthesis of the chiral side-chain of statins: application of an alcohol dehydrogenase catalysed ketone reduction on a large scale

“…Application of cofactor regeneration systems that require additional enzymes are avoided, thus. The excess of 2-propanol is supposed to be the driving force of the reaction and a conversion of more than 90% is attained in this manner (Scheme 6) [29]. 4 In first preparative enzymatic reductions we noted that diketo ester 10 undergoes a pH-dependent intramolecular alkylation to give significant amounts of furanone 18 as non-enzymatic by-product.…”

Hydroxynitrile Lyase in Organic Solvent‐Free Systems to Overcome Thermodynamic Limitations

“…That such studies are indeed possible has been shown recently for the enantioselective ketone reduction using alcohol dehydrogenases. [41,42] The potential of the approach presented here was proven by synthesis of 5 mL of (S)-acetophenone cyanohydrin with an enantiomeric excess of 98.5 % ee (S). This included also a distillation step without any decomposition or racemization of the product.…”