Production of High Value Amine Intermediates via Biocatalytic Cascades in Continuous Flow

Baldwin, C; Thompson, MP; Turner, N; Pamer, R; Ford, G; Citoler, J; Mattey, AP; Marshall, J; Flitsch, S; Cosgrove, S

Abstract

<jats:p>A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out compartmentalized multistep cascades in a controlled and selective way. As biocatalytic cascades get longer and more complex, reactions become unattainable under typical batch conditions. Here a continuous flow multipoint injection reactor was combined with switching valves to overcome batch incompatibility, thus allowing for successful biocatalytic reaction cascades. As proof-of-principle, several reactive carbonyl intermediates were generated <jats:italic>in situ </jats:italic>using galactose oxidase and engineered choline 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 <jats:italic>via </jats:italic>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 alkaloid precursor 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.</jats:p>

Citation

Baldwin, C., Thompson, M., Turner, N., Pamer, R., Ford, G., Citoler, J., Mattey, A., Marshall, J., Flitsch, S., & Cosgrove, S. (2021). Production of High Value Amine Intermediates via Biocatalytic Cascades in Continuous Flow. ChemRxiv, https://doi.org/10.26434/chemrxiv.14039141.v1

• Acceptance Date: Feb 17, 2021
• Online Publication Date: Feb 17, 2021
• Publication Date: Feb 17, 2021
• Journal: Organic Chemistry
• Print ISSN: 2573-2293
• Publisher: Cambridge University Press
• Peer Reviewed: Not Peer Reviewed
• DOI: https://doi.org/10.26434/chemrxiv.14039141.v1
• Public URL: https://keele-repository.worktribe.com/output/421397
• Publisher URL: https://chemrxiv.org/engage/chemrxiv/article-details/60c75511842e659747db429a
• Related Public URLs: https://chemrxiv.org/engage/chemrxiv/article-details/60c75511842e659747db429a