Development of continuous flow systems to access secondary amines through previously incompatible biocatalytic cascades.

Mattey, Ashley P.; Ford, Grayson J.; Citoler, Joan; Baldwin, Christopher; Marshall, James R.; Palmer, Ryan B.; Thompson, Matthew; Turner, Nicholas J.; Cosgrove, Sebastian C.; Flitsch, Sabine L.

Abstract

A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out multistep cascades in a controlled and selective way. As biocatalytic cascades get more complex, reactions become unattainable under typical batch conditions. Here a number of continuous flow systems were used to overcome batch incompatibility, thus allowing for successful biocatalytic cascades. As proof-of-principle, reactive carbonyl intermediates were generated in situ using alcohol oxidases, then passed directly to a series of packed-bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade via an oxidase/transaminase/imine reductase sequence, introducing different amine reagents at each step without cross reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product 4O-methylnorbelladine. The flow biocatalysis platform shown here significantly increases the scope of novel biocatalytic cascades, removing previous limitations due to reaction and reagent batch incompatibility.

Citation

Mattey, A. P., Ford, G. J., Citoler, J., Baldwin, C., Marshall, J. R., Palmer, R. B., …Flitsch, S. L. (2021). Development of continuous flow systems to access secondary amines through previously incompatible biocatalytic cascades. Angewandte Chemie International Edition, 60(34), 18660-18665. https://doi.org/10.1002/anie.202103805

• Journal Article Type: Article
• Acceptance Date: Apr 15, 2021
• Online Publication Date: May 19, 2021
• Publication Date: Aug 16, 2021
• Publicly Available Date: Jun 26, 2023
• Journal: Angewandte Chemie International Edition
• Print ISSN: 1433-7851
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 60
• Issue: 34
• Pages: 18660-18665
• DOI: https://doi.org/10.1002/anie.202103805
• Keywords: General Chemistry, Catalysis
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/anie.202103805