Consecutive and Cascade One-Pot Reductions

Thanks to the availability of highly regio- and enantioselective reductive enzymes, namely, NADPH-dependent ketoreductases (KREDs), it has been recently demonstrated that consecutive reductions of substrates bearing two or more keto groups can be easily carried out in the same reaction vessel and without the isolation of the intermediates. 

Single diastereomers of the diol products were obtained by a two-step process after careful selection of the biocatalysts. In the first reduction step, the starting substrate was completely converted into the corresponding P-hydroxy ketone by the first KRED enzyme without any further reduction to the 1,3-diol. Reduction reactions were coupled with the glucose/glucose dehydrogenase (GDH) system for the in situ regeneration of the reduced cofactor. The second KRED enzyme was then added to 

As both HLADH show an almost absolute chemoselectivity in favor of the saturated aldehydes and OYE3 (or OYE2) is not able to reduce the C=C double bond of the unsaturated alcohol for the lack of a suitable electron-withdrawing group, the cascade process can only proceed through the intermediate saturated aldehyde. 

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