Cuvillier
Enantioselective enzymatic reduction of prochiral ketones in one-phase and two-phase systems
Abstract
dc:descriptionWithin this thesis a strategy for the enantioselective synthesis of chiral short chain alcohols using biocatalysis is developed. This is realized in close collaboration with an industrial partner. The biocatalysts used are alcohol dehydrogenases (ADH) which need nicotinamide cofactors (NAD+/NADH and NADP+/NADPH) as redox equivalents. The regeneration of the cofactors is done substrate dependent by addition of 2-propanol which is oxidized by the ADH while the cofactor is reduced, and enzyme dependent. Here, a malate dehydrogenase(MDH) as second enzyme and L-malic acid as specific substrate are used for in situ cofactor reduction. The kinetic characterization of the different ADH preparations and of a NAD- and a NADP-dependent MDH shows strong dependence of activity on the substrate, on reaction parameters like concentrations of buffer, substrate, and cofactor, on the type of ADH and on the kind of preparation, i.e. lyophilized or purified. The obtained results are transferred to one-phase batch synthesis of (R)- and (S)-2-butanol. Conversion and enantioselectivity (ee) are dependent on reaction conditions, i.e. 2-propanol and substrate concentration. Generally it is possible to synthesis both enantiomers of 2-butanol in the one-phase system. Due to limitations like low conversion, low selectivity, and low substrate solubility the synthesis of (R)-2-butanol is transferred to two-phase reaction systems using methyl-tert-butyl ether(MTBE) and the tailor-made ionic liquid (IL) as non-reactive phase. MTBE turns out to be the solvent of choice. Depending on substrate and co-substrate concentration conversion and ee can be positively influenced. The same is found for two-phase reactions with MTBE in a continuous reaction set-up. With the optimum reaction conditions obtained from the batch experiments conversion and ee are improved. Another influencing factor in the continuous reaction is the flow rate. 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 alcohols on preparative relevant scale.
Degree
thesis:*- Grantor dc:publisher
- Cuvillier
- Year dc:date
- 2010
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Müller, Pia
- Contributors dc:contributor
-
- Leitner, Walter
Subjects
dc:subject × 9Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- eng