Reaction Engineering of Biocatalytic Enantioselective Reduction: A Case for Aliphatic Ketones

S. Leuchs, J. Lima-Ramos, L. Greiner, N. Al-Haque, P. Tufvesson, J. Woodley

Org. Process Res. Dev., 17/8 (2013), 1027-1035, doi: 10.1021/op400117t


Previously, it could be demonstrated, that the monophasic, enzymatic reduction of aliphatic 2-ketones into the corresponding (R)-2-alcohols is an adequate and viable method as carried out in a cascade of two enzyme–membrane reactors (Leuchs, S.; Na’amnieh, S. N.; Greiner, L. Green Chemistry 2013, 15, 167–176.). In the present work, the process metrics of the ketone reduction were calculated. A cost analysis revealed that the enzyme costs are negligible, but the cost for nicotinamide cofactor NADP+ is dominating the overall cost of the chemical raw material followed by the ionic liquid (TEGO IL K5) used as solubiliser and the buffer. The overall cost of chemicals was €148/kgproduct. To assess the environmental impact of the process, the E-factor (kgwaste/kgproduct) 132 and the process mass intensity 133 (PMI, kgsubstrate/kgproduct) were calculated. A process model based on initial rate experiments was elaborated and used to improve the process under cost and environmental aspects. Applying several measures to enhance the cofactor utilisation, the cost base could be reduced by 65% and the E-factor (PMI) to 17 (18).

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