Reaction engineering for biocatalytic reduction processes

The analysis of reaction enantioselectivity for asymmetric reductions is key for the process development and an interesting combined use of high-performance liquid chromatography and circular dichroism has led to an efficient procedure for alcohol dehydrogenase-catalyzed asymmetric reduction of l-phenyl-2-propyn-3-trimethyl-silyl-l-on [133]. 

The bottleneck of substrate and product toxidty to the microbial cells used for the reduction has been overcome by the use of a polymeric resin to both supply substrate to and remove the product from the reaction mixture and therefore the microbial cells in the biocatalytic reduction of 3,4-methylene-dioxyphenyl acetone by Zygosacchar-omyces rouxii to the corresponding (S)-3,4-methylene-dioxyphenyl isopropanol in 95% isolated yield and with 99.9% enantiomeric excess [134]. This substrate feed and product recovery (SFPR) design made it possible to increase concentration from 6 to 40 g/1 and to achieve the reaction, product isolation, and resin recycling within a single piece of equipment at an overall reactor productivity of 75 g/l/day. 

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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