Electroenzymatic Asymmetric Reduction of rac‐3‐Methylcyclohexanone to (1S,3S)‐3‐Methylcyclohexanol in Organic/Aqueous Media Catalyzed by a Thermophilic Alcohol Dehydrogenase

Abstract

Electrochemical regeneration of nicotinamide cofactors has been discussed as a promising, clean, and sustainable technology since the 1980s. However, most concepts for the coupling of this technology to enzymes suffer from low productivities, insufficient stabilities, or are difficult to scale up. We have developed an electrochemical cell for the efficient regeneration of NAD(P)H, which can be coupled to a reduction reaction catalyzed by the thermophilic alcohol dehydrogenase from Thermus sp. Octane, as second organic phase avoided product inhibition and allowed for the production of (1S,3S)-3-methylcyclohexanol at a diastereomeric excess of 96 % from the corresponding racemic ketone with a productivity of 0.13 g L À1 h À1 and a current efficiency of 85 %. After 10 h, the experiment was actively terminated and the final product concentration reached was 1.32 g L À1. In our opinion this concept defines a new state of the art in electroenzymology and provides a strong basis for applications in organic synthesis.

Enzymatic production of 2-amino-2,3-dimethylbutyramide by cyanide-resistant nitrile hydratase

“…A biphasic approach using water-immiscible organic solvent has been extensively employed in the biotransformation, for the sake of minimizing the inhibition of substrate and/or product [7,13]. In this study, n-hexane was found to be favorable for the NHase-catalyzed hydration of ADBN and selected as co-solvent to set up a biphasic system.…”

“…As a result, reduction of NHase inhibition by cyanide or screening of NHase tolerant to cyanide is crucial for the industrial bioproduction of -aminoamides. Another approach is to use water-immiscible organic solvent to establish a biphasic system, which can minimize inhibition of substrate and/or product [7,13]. Although biphasic system has been well established in many biocatalytic processes, its application in NHase-mediated bioconversion is rarely reported.…”

Asymmetric Electrochemical Catalysis

“…Later, Schmid and co‐workers reported the use of Rh complex 21 b as a NADPH‐recycle mediator. In this reaction system, thermophilic NAD‐dependent alcohol dehydrogenase (TADH) was used as a biocatalyst to promote the hydrogenation of cyclohexanone 21 a but the enantioselectivity was not reported in this study (Scheme ) …”

“…In this reaction system, thermophilic NAD-dependent alcohol dehydrogenase( TADH) was used as ab iocatalyst to promote the hydrogenation of cyclohexanone 21 a but the enantioselectivity was not reportedi n this study (Scheme 21). [44] Electrochemical processes have also been appliedi n enzyme-mediated oxidation reactions. StyA is an FADH 2 -dependent oxygenase belonging to the styrene monooxygenase (StyAB) family for specific S-selective epoxidation of styrenes.…”

Novel Developments Employing Redox Enzymes: Old Enzymes in New Clothes

“…Furthermore, electrochemical methods have been realized for recycling of the cofactor. All these approaches have recently been reviewed [13,14,[63][64][65][66][67][68][69][70]. Obviously, the simplest method is the coupledsubstrate approach [71].…”