Application L1703 Cover React. Chem. Eng. Issue 4, 2017

Reaction engineering of biocatalytic (S)-naproxen synthesis integrating in-line process monitoring by Raman spectroscopy

M. Aßmann, A. Stöbener, C. Mügge, S. K. Gaßmeyer, L. Hilterhaus, R. Kourist, A. Liese, and S. Kara

React. Chem. Eng., 2017, 2(4), pp. 531-540.

“Biocatalytic (S)-naproxen synthesis using an (S)-selective arylmalonate decarboxylase mutant (AMDase G74C/M159L/C188G/V43I/A125P/V156L, AMDase-CLGIPL) exposes a promising environmentally friendly alternative to conventional chemical synthesis strategies. The reaction progress of naproxen synthesis catalyzed by AMDase-CLGIPL covalently immobilized onto a robust acrylate carrier was investigated with respect to reaction engineering. Kinetic characterization of the immobilized enzyme reveals a K_M value of 22.1 ± 0.1 mM in the naproxen malonate conversion and an inhibiting effect of the produced naproxen with a K_i of 26.3 ± 1.4 mM. However, an effective process can be realized without in situ product removal yielding (S)-naproxen with an ee of 99%. By optimizing the product work-up, an isolated yield of 92% was achieved with total turnover numbers between 83,000 and 107,000 in five repetitive batches. Furthermore, process monitoring with in-line Raman spectroscopy was successfully applied to analyze the reaction progress with a root mean square error of prediction of 0.8 mM (corresponding to 4%).”




  • A traditional stirred tank reactor setup was compared to a rotating bed reactor (RBR) for the biocatalytic synthesis of the anti-inflammatory drug (S)-naproxen. Both setups performed well during five repetitive bathes giving an enantiomeric excess of 99% and an isolated yield of 92%, but the RBR was easier to handle and the authors concluded that “[…] the rotating bed reactor concept can be regarded as a promising option for industrial applications”.

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