Reduction enzyme-mediated asymmetric

The catalytic, asymmetric hydrogenations of alkenes, ketones and imines are important transformations for the synthesis of chiral substrates. Organic dihydropyridine cofactors such as dihydronicotinamide adenine dinucleotide (NADH) are responsible for the enzyme-mediated asymmetric reductions of imines in living systems [86]. A biomimetic alternative to NADH is the Hantzsch dihydropyridine, 97. This simple compound has been an effective hydrogen source for the reductions of ketones and alkenes. A suitable catalyst is required to activate the substrate to hydride addition [87-89]. Recently, two groups have reported, independently, the use of 97 in the presence of a chiral phosphoric acid (68 or 98) catalyst for the asymmetric transfer hydrogenation of imines. 

Unless specified otherwise, all reductions included in this chapter gave good yields of >90% enantiomeric excess (ee) products. Not all products of enzyme-catalyzed reactions meet the minimum % ee levels normally required for asymmetric synthetic applications. However, protocols exist for improving ee s of imperfectly specific enzyme-mediated transformations. 

R and Moran, P.J.S. (2004) Baker s yeast mediated asymmetric reduction of cinnamaldehyde derivatives./. Mol. Catal. B Enzym., 29,41 5. 

Recently, Stewart and coworkers developed the alkene reductase-mediated asymmetric reduction of citral to produce both enantiomers of citronellal on gram-scale where a strategy of biphasic conditions (1 1 hexanes and phosphate buffer) was adopted to protect enzymes from deactivation by the citral feedstock (Figure 9.3). High conversions of >95% were achieved, yielding (R)- and (S)-citronellal with excellent enantioselectivity of >98%, thus opening the possibility of employing alkene reductases in preparative-scale reactions [28]. 

For the asymmetric reduction of ketone and aldehyde derivates, two electrochemical reduction systems using ADH as catalyst were examined (Fig. 22) [108]. In system A, the reduced coenzymes are regenerated using either FNR for NADPH or DP for NADH. Methyl viologen serves as electron mediator between the electrode and FNR/DP. System B contains ADH as sole enzyme, which catalyzes both reduction of substrates and regeneration of cofactors. Phenylethanol is oxidized by ADH accompanied by reduction of NADP+ to NADPH and its oxidation product acetophenone is reduced electrochemically at a glassy carbon cathode. 

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