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

Research output: Contribution to journalArticle

  • External authors:
  • Scott P. France
  • Godwin A. Aleku
  • Mahima Sharma
  • Juan Mangas-Sanchez
  • Roger M. Howard
  • Jeremy Steflik
  • Rajesh Kumar
  • Iustina Slabu
  • Robert Crook
  • Gideon Grogan

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.

Bibliographical metadata

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

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