1. Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines
- Author
-
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, and Nicholas J. Turner
- Subjects
reductases ,biocatalysis ,Stereochemistry ,Imine ,010402 general chemistry ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,Molecule ,Azepine ,Retrosynthetic analysis ,Conformational isomerism ,Transaminases ,transaminases ,Oxidoreductases Acting on CH-NH Group Donors ,heterocycles ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Stereoisomerism ,Azepines ,General Medicine ,General Chemistry ,0104 chemical sciences ,3. Good health ,Enantiopure drug ,Biocatalysis ,synthetic methods ,Chirality (chemistry) - 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.
- Published
- 2017