Mattey, A, Ford, G, Citoler, J, Baldwin, C, Marshall, J, Palmer, R, Thompson, M, Turner, N, Cosgrove, SC and Flitsch, S (2021) Development of continuous flow systems to access secondary amines through previously incompatible biocatalytic cascades. Angewandte Chemie International Edition. ISSN 1433-7851

[thumbnail of Mattey et al final manuscript.pdf] Text
Mattey et al final manuscript.pdf - Accepted Version
Restricted to Repository staff only
Available under License Creative Commons Attribution Non-commercial.

Download (687kB)
[thumbnail of Development of continuous flow systems to access secondary amines through previously incompatible biocatalytic cascades.pdf]
Preview
Text
Development of continuous flow systems to access secondary amines through previously incompatible biocatalytic cascades.pdf
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview

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.

Item Type: Article
Additional Information: The final version of this accepted manuscript and all relevant information related to it, including copyrights, can be found online at; https://onlinelibrary.wiley.com/doi/10.1002/anie.202103805
Uncontrolled Keywords: biocatalytic cascades; continuous flow; oxidation; reductive amination; transamination
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 30 Apr 2021 08:36
Last Modified: 15 Apr 2022 01:30
URI: https://eprints.keele.ac.uk/id/eprint/9459

Actions (login required)

View Item
View Item