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

TY - JOUR

T1 - Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines

AU - France, Scott P.

AU - Aleku, Godwin A

AU - Sharma, Mahima

AU - Mangas-Sanchez, Juan

AU - Howard, Roger M

AU - Steflik, Jeremy

AU - Kumar, Rajesh

AU - Adams, Ralph W

AU - Slabu, Iustina

AU - Crook, Robert

AU - Grogan, Gideon

AU - Wallace, Timothy W

AU - Turner, Nicholas John

N1 - © 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2017/12/4

Y1 - 2017/12/4

N2 - 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.

AB - 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.

KW - biocatalysis

KW - heterocycles

KW - reductases

KW - synthetic methods

KW - transaminases

UR - http://www.scopus.com/inward/record.url?scp=85035104207&partnerID=8YFLogxK

U2 - 10.1002/anie.201708453

DO - 10.1002/anie.201708453

M3 - Article

C2 - 29024400

SN - 1433-7851

VL - 56

SP - 15589

EP - 15593

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 49

ER -