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Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic Cascades **
Author(s) -
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.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103805
Subject(s) - biocatalysis , chemistry , flow chemistry , combinatorial chemistry , amination , amine gas treating , reagent , cascade reaction , imine , reductive amination , cascade , organic chemistry , reaction mechanism , catalysis , chromatography
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.