Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades**

Cosgrove, Sebastian C.

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.

Citation

Cosgrove, S. C., Mattey, A. P., Ford, G. J., Citoler, J., Baldwin, C., Marshall, J. R., …Flitsch, S. L. (2021). Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades**. Angewandte Chemie, 133(34), 18808-18813. https://doi.org/10.1002/ange.202103805

• Journal Article Type: Article
• Acceptance Date: Apr 15, 2021
• Online Publication Date: Apr 15, 2021
• Publication Date: Aug 16, 2021
• Journal: Angewandte Chemie
• Print ISSN: 0044-8249
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 133
• Issue: 34
• Pages: 18808-18813
• DOI: https://doi.org/10.1002/ange.202103805
• Keywords: General Medicine
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/ange.202103805