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dc.contributor.authorAleku, Godwin A
dc.contributor.authorTitchiner, Gabriel R
dc.contributor.authorRoberts, George W
dc.contributor.authorDerrington, Sasha R
dc.contributor.authorMarshall, James R
dc.contributor.authorHollfelder, Florian
dc.contributor.authorTurner, Nicholas J
dc.contributor.authorLeys, David
dc.date.accessioned2022-07-02T01:08:55Z
dc.date.available2022-07-02T01:08:55Z
dc.date.issued2022-05-23
dc.identifier.issn2168-0485
dc.identifier.otherPMC9131517
dc.identifier.other35634269
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338703
dc.description.abstractAllylic amines are a versatile class of synthetic precursors of many valuable nitrogen-containing organic compounds, including pharmaceuticals. Enzymatic allylic amination methods provide a sustainable route to these compounds but are often restricted to allylic primary amines. We report a biocatalytic system for the reductive N-allylation of primary and secondary amines, using biomass-derivable cinnamic acids. The two-step one-pot system comprises an initial carboxylate reduction step catalyzed by a carboxylic acid reductase to generate the corresponding α,β-unsaturated aldehyde in situ. This is followed by reductive amination of the aldehyde catalyzed by a bacterial reductive aminase pIR23 or BacRedAm to yield the corresponding allylic amine. We exploited pIR23, a prototype bacterial reductive aminase, self-sufficient in catalyzing formal reductive amination of α,β-unsaturated aldehydes with various amines, generating a broad range of secondary and tertiary amines accessed in up to 94% conversion under mild reaction conditions. Analysis of products isolated from preparative reactions demonstrated that only selective hydrogenation of the C=N bond had occurred, preserving the adjacent alkene moiety. This process represents an environmentally benign and sustainable approach for the synthesis of secondary and tertiary allylic amine frameworks, using renewable allylating reagents and avoiding harsh reaction conditions. The selectivity of the system ensures that bis-allylation of the alkylamines and (over)reduction of the alkene moiety are avoided.
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2168-0485
dc.sourcenlmid: 101608852
dc.titleEnzymatic N-Allylation of Primary and Secondary Amines Using Renewable Cinnamic Acids Enabled by Bacterial Reductive Aminases.
dc.typeArticle
dc.date.updated2022-07-02T01:08:54Z
prism.endingPage6806
prism.issueIdentifier20
prism.publicationNameACS Sustain Chem Eng
prism.startingPage6794
prism.volume10
dc.identifier.doi10.17863/CAM.86116
rioxxterms.versionofrecord10.1021/acssuschemeng.2c01180
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidAleku, Godwin A [0000-0003-0969-5526]
dc.contributor.orcidHollfelder, Florian [0000-0002-1367-6312]
dc.contributor.orcidTurner, Nicholas J [0000-0002-8708-0781]
dc.contributor.orcidLeys, David [0000-0003-4845-8443]
dc.identifier.eissn2168-0485
pubs.funder-project-idEuropean Research Council (695669, 695013)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P000622/1)
cam.issuedOnline2022-05-06


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International