Stereoselective synthesis of vicinal diols with enzymatic cascade reactions

Alcohol dehydrogenases are of high interest for the stereoselective synthesis of building blocks with multi-chiral centres. They are implemented for single enzymatic reduction or oxidation steps or be part of synthetic enzymatic multi-step cascades for the production of industrially relevant chiral synthons. Although biotransformations with alcohol dehydrogenases are widespread, enzymes, which accept sterically demanding substrates, especially α-hydroxy ketones, are not common in nature. Therefore chemical methods for the synthesis of chiral 1,2-diols are still first choice. As a drawback, alcohol dehydrogenases require expensive nicotinamide cofactors such as NAD(H) or NADP(H) for their activity. Prices of these cofactors prevent their application in stoichiometric amounts and therefore regeneration of nicotinamide cofactors is an essential issue for biotechnological purposes. Therefore a co-substrate is required that is transformed to the respective co-product in equimolar amounts relative to the product. This co-product has to be separated from the product or must be removed in situ, which decreases atom- and process economy. In this work the carboligation of two inexpensive aldehydes catalysed by ThDPdependent enzymes is combined with a subsequent reduction of the intermediately formed α-hydroxy ketone by alcohol dehydrogenases. Therefore, a suitable cofactor regeneration system with smart in situ co-product removal had to be developed in order to gain high eco-efficiency of the synthetic enzyme cascade. To achieve the aim, the following work packages were addressed: ...