Substrate-coupled biocatalytic reduction

Table 8.5 Representative examples of substrate-coupled biocatalytic reduction reactions.

Scheme 8.8 The substrate-coupled regeneration of NAD(P) H as the biocatalytic variant of the Meerwein-Ponndorf-Verley (MPV) reduction.

The use of organic solvents as reaction media for biocatalytic reactions can not only overcome the substrate solubility issue, but also facilitate the recovery of products and biocatalysts as well. This technique has been widely employed in the case of lipases, but scarcely applied for biocatalytic reduction processes, due to the rapid inactivation and poor stability of redox enzymes in organic solvents. Furthermore, all the advantages for nonaqueous biocatalysis can take effect only if the problem of cofactor dependence is also solved. Thus, bioreductions in micro- or nonaqueous organic media are generally restricted to those with substrate-coupled cofactor regeneration. 

Figure 9.4 Biocatalytic reduction of acetophenone and 3-butyn-2-one using lyophilized coli cells with overexpressed carbonyl reductase in neat substrates with isopropanol-coupled cofactor regeneration.

Another potential bottleneck to be overcome is the inherent equilibrium problem associated with the coupled substrate approach to biocatalytic carbonyl reduction and in situ product removal allowed the isolation of the pure (S)-2-bromo-2-cyclohexen-l-ol in 88% yield and with 99.8% enantiomeric excess [135]. 

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