Reduction electroenzymatic

The successful synthetic application of this electroenzymatic system has first been shown for the in-situ electroenzymatic reduction of pyruvate to D-lactate using the NADH-dependent D-lactate dehydrogenase. Electrolysis at — 0.6 V vs a Ag/AgCl-reference electrode of 50 mL of a 0.1 M tris-HCL buffer of pH 7.5 containing pentamethylcyclopentadienyl-2,2 -bipyridinechloro-rhodium(III) (1 x 10 3 M), NAD+ (2 x 10 3 M), pyruvate (2 x 10 2 M), 1300 units D-lactate dehydrogenase (divided cell, carbon foil electrode) after 3 h resulted in the formation of D-lactate (1.4 x 10 2 M) with an enantiomeric excess of 93.5%. This means that the reaction occurred at a rate of 5 turnovers per hour with respect to the mediator with a 70% turnover of the starting material. The current efficiency was 67% [67],... 

Fig. 17. Electroenzymatic reduction of 4-phenyI-2-butanone catalyzed by HLADH with in-situ indirect electrochemical regeneration of NADH using a Cp (2,2 -bipyridyl)aquo rhodium(III) complex as mediator...

The same authors proposed a complex system for the electrochemically driven enzymatic reduction of carbon dioxide to form methanol. In this case, methyl viologen or the cofactor PQQ were used as mediators for the electroenzymatic reduction of carbon dioxide to formic acid catalyzed by formate dehydrogenase followed by the electrochemically driven enzymatic reduction of formate to methanol catalyzed by a PQQ-dependent alcohol dehydrogenase. With methyl viologen as mediator, the reaction goes through the intermediate formation of formaldehyde while with PQQ, methanol is formed directly [77],... 

Simon H, Bader J, Gunther H, Neumann S, Thanos J (1984) Biohydrogenation and elec-tromicrobial and electroenzymatic reduction methods for the preparation of chiral compounds, Ann NY Acad Sci 434 171, and refs therein... 

Scheme 32 Electroenzymatic reduction of ketones with alcohol dehydrogenase Rh aryl, R alkyl, CHO, CO2H, yields 92-100%, 0 - 100% ee.

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

This system has been successfully applied to the in-situ electroenzymatic reduction of pyruvate to D-lactate using the NADH-dependent D-lactate dehydrogenase or the reduction of 4-phenyl-2-butanone to (5)-4-phenyl-2-butanol using the NADH-dependent horse liver alcohol dehydrogenase (HLADH) with high enantioselectivity (Fig. 22.4) [65]. 

Simon and collaborators have described a novel stereoselective electroenzymatic reduction of alkenes of type 23 (equation 12)28. The enzyme enoate reductase is the reductant... 

Ruinatscha R, Hollrigl V et al (2006) Productivity of selective electroenzymatic reduction and oxidation reactions theoretical and practical considerations. Adv Synth Catal 348 2015-2026... 

Robert, M. and Saveant, l.-M. (2005) Electroenzymatic reactions. Investigation of a reductive dehalogenase by means of electrogenerated redox cosubstrates. 1. Am. Chem. Soc. 127, 13583-13588. 

This system has been efficiently applied in the in situ electroenzymatic reduction of pyruvate to D-lactate by means of the NADH-dependent D-lactate dehydrogenase (Fig. 23). Using pentamethylcyclopentadienyl-2-2 -bipyridinechloro-rhodium(III) ([Cp Rh(bpy)Cl]Cl) as redox catalyst, D-lactate was formed with an ee value of 93.5% after 3 h at a rate of five turnovers per hour [112]. 

The electroenzymatic reduction of NAD+ was successfully coupled with a synthesis reaction [122]. Hydrogenase from A. eutrophus was applied to regenerate NADH electrochemically during the transformation of a-ketoglutarate into L-glutamate catalyzed by an L-glutamate dehydrogenase (Fig. 27). 

Figure 8. Methyl viologen-mediated electroenzymatic reduction of pyruvate to o-lactate using lipoamide dehydrogenase (LiDH) and cross-linked enzyme crystals of o-lactate dehydrogenase [49],...

Figure 9. Acetophenone-mediated electroenzymatic reduction of l-phenoxy-2-propanone to (5 )-1 -phenoxy-2-propanol using lipoamide dehydrogenase (LiDH) or ferredoxin-NADP reductase (FNR) and an alcohol dehydrogenase [46].

Similarly, the pyruvate (oxidase) dehydrogenase complex (PYOX) can be activated directly by electrogenerated methyl viologen radical cations (MV" ) as mediator. Thus, the naturally PYOX-catalyzed oxidative decarboxylation of pyruvic acid in the presence of coenzyme A (HSCoA) to give acetylcoenzyme A (acetyl-SCoA) (see section on oxidases) can be reversed. In this way, electroenzymatic reductive carboxylation of acetyl-SCoA is made possible (Fig. 15). 

Figure 15. Electroenzymatic reductive carboxylation of acetyl-SCoA to give pyruvate.

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