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

Cosgrove, Sebastian C.

doi:10.1002/ange.202103805

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

Cosgrove, Sebastian C.

Authors

Sebastian Cosgrove s.cosgrove@keele.ac.uk

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.

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