Application L2001 Cover OPRD, Volume 23, 2019

Using SpinChem rotating bed reactor technology for immobilized enzymatic reactions: A case study

Subhash Pithani, Staffan Karlsson, Hans Emtenäs, and Christopher T. Öberg

Org. Process Res. Dev., 2019, 23(9), pp. 1926-1931.

“The practically and financially viable use of immobilized enzymes in the production of pharmaceutical and bulk chemicals requires highly catalytically active enzymes and efficient mass transfer of substrate to the active site. The substantial cost of immobilized enzymes further mandates extended reuse of the enzymes to keep operating expenditures down. The extent of reuse of immobilized enzymes depends on parameters such as enzyme long-term stability under process conditions, carrier integrity and attrition due to mechanical stress, and ease of workup and recovery on scale. Herein, we report on the use of a SpinChem rotating bed reactor (RBR) for the Novozyme 435 mediated kinetic resolution of (cis)-isopropyl 3-aminocyclohexanecarboxylate as an alternative to the traditional reaction using free-flowing immobilized lipases in an ordinary batch reactor. Reusability was studied in addition to other parameters such as type of immobilized enzyme, loading, rate of agitation, temperature, and scalability. By using SpiChem RBR technology, we found that recycling of the immobilized enzyme was easy with preserved enantioselectivity and catalytic activity. The final optimized process was successfully demonstrated on a 1 kg scale with 39% isolated yield and 98.8% enantiomeric purity.”

 

Highlights:

  • "By using SpinChem RBR technology, we found that recycling of the immobilized enzyme was easy with preserved enantioselectivity and catalytic activity. The final optimized process was successfully demonstrated on a 1 kg scale with 39% isolated yield and 98.8% enantiomeric purity.”
  • "We found that the immobilized enzyme was surprisingly stable under these conditions and we could run 10 consecutive recycling experiments with preserved rate of reaction and enantioselectivity of the enzyme (∼90% ee [of crude])”

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