Promiscuous Substrate Binding Explains the Enzymatic Stereo- and Regiocontrolled Synthesis of Enantiopure Hydroxy Ketones and Diols

Regio‐ and stereoselective reductions of several diketones to afford enantiopure hydroxy ketones or diols were accomplished using isolated alcohol dehydrogenases (ADHs). Results could be rationalised taking into account different (promiscuous) substrate‐binding modes in the active site of the enzyme. Furthermore, interesting natural cyclic diketones were also reduced with high regio‐ and stereoselectivity. Some of the 1,2‐ and 1,3‐diketones used in this study were reduced by employing a low excess of the hydrogen donor (2‐propanol) due to the quasi‐irreversibility of these ADH‐catalysed processes. Thus, using lower quantities of co‐substrate, scale‐up could be easily achieved.