engleski

Multi-enzyme cascade reaction for the synthesis of statin sidechain precursors

Statins are a class of medicine that lower the level of low-density lipoprotein (LDL) cholesterol in blood. The modern requirements for stereochemical purity (ee > 99.5%, de > 99%) have created new challenges for industrial preparation of statins. One of the ways to achieve the required enantio- and diastereopurities is the use of biocatalysis [1]. In this work, a cascade reaction with three enzymes was investigated for the synthesis of statin side-chain precursors (Figure 1). The first reaction in this cascade is the oxidation of an alcohol to aldehyde catalyzed by an alcohol dehydrogenase. The second enzyme was NADH oxidase which was used for coenzyme regeneration. The final product of this reaction is a lactol which is formed in the aldol addition of acetaldehyde and the corresponding aldehyde catalyzed by deoxyribose-phosphate aldolase. Acetaldehyde has a negative influence on enzyme activity in high concentrations, so for this reaction a fed-batch reactor was chosen as the best reactor type and this cascade reaction was carried out with acetaldehyde feed.

biocatalysis, cascade reaction, statin-side chain, fed-batch reactor

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