Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines

Scott P. France, Godwin A. Aleku, Mahima Sharma, Juan Mangas-Sanchez, Roger M. Howard, Jeremy Steflik, Rajesh Kumar, Ralph W. Adams, Iustina Slabu, Robert Crook, Gideon Grogan, Timothy W. Wallace, Nicholas J. Turner

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    Abstract

    Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and ω-transaminase (ω-TA) biocatalysts to establish the key stereocentres of these molecules. Several enantiocomplementary IREDs were identified for the synthesis of (R)- and (S)-5-methyl-6,7-dihydro-5H-dibenz[c,e]azepine with excellent enantioselectivity, by reduction of the parent imines. Crystallographic evidence suggests that IREDs may be able to bind one conformer of the imine substrate such that, upon reduction, the major product conformer is generated directly. ω-TA biocatalysts were also successfully employed for the production of enantiopure 1-(2-bromophenyl)ethan-1-amine, thus enabling an orthogonal route for the installation of chirality into dibenz[c,e]azepine framework.

    Original languageEnglish
    Pages (from-to)15589-15593
    Number of pages5
    JournalAngewandte Chemie - International Edition
    Volume56
    Issue number49
    Early online date12 Oct 2017
    DOIs
    Publication statusPublished - 2017

    Keywords

    • biocatalysis
    • heterocycles
    • reductases
    • synthetic methods
    • transaminases

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