Enantioselective Enzymatic Reduction of Prochiral Ketones in One-Phase and Two-Phase Systems

A strategy for the enantioselective synthesis of chiral short

chain alcohols using biocatalysis is developed employing

substrate and enzyme dependent in situ cofactor

regeneration. Enzyme characterization shows strong

dependence of activity on diverse reaction parameters. The

obtained results are transferred to one-phase batch synthesis

of (R)- and (S)-2-butanol where conversion and

enantioselectivity are strongly dependend on reaction

conditions. Due to limitations like low substrate solubility the

synthesis is transferred to two-phase reaction systems where

MTBE is the solvent of choice. Conversion and selectivity are

positively influenced. The same is found for two-phase

reactions in a continuous reaction set-up. With the optimum

reaction conditions obtained from the batch experiments

conversion and selectivity are improved. ADH and cofactor

show exceptionally high stability and high TTN. Together with

further development of a work-up strategy the continuous

two-phase reaction set-up will be a strong tool to produce

enantiopure short chain alcohols on preparative relevant

scale.