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Biocatalytic routes to enantiomerically enriched dibenz[c,e]azepines
Authors:
Scott P.
France
(University of Manchester)
,
Godwin A.
Aleku
(University of Manchester)
,
Mahima
Sharma
(University of York)
,
Juan
Mangas-Sanchez
(University of Manchester)
,
Roger M.
Howard
(Pfizer Worldwide Research and Development)
,
Jeremy
Steflik
(Pfizer Worldwide Research and Development)
,
Rajesh
Kumar
(Pfizer Worldwide Research and Development)
,
Ralph W.
Adams
(University of Manchester)
,
Iustina
Slabu
(University of Manchester)
,
Robert
Crook
(Pfizer Worldwide Research and Development)
,
Gideon
Grogan
(University of York)
,
Timothy W.
Wallace
(University of Manchester)
,
Nicholas J.
Turner
(University of Manchester)
Co-authored by industrial partner:
Yes
Type:
Journal Paper
Journal:
Angewandte Chemie International Edition
, VOL 56
, PAGES 15589 - 15593
State:
Published (Approved)
Published:
November 2017
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.
Journal Keywords: biocatalysis; heterocycles; reductases; synthetic methods; transaminases
Diamond Keywords: Enzymes
Subject Areas:
Chemistry,
Biology and Bio-materials
Instruments:
I04-1-Macromolecular Crystallography (fixed wavelength)
Added On:
30/05/2018 10:02
Discipline Tags:
Biochemistry
Catalysis
Chemistry
Structural biology
Organic Chemistry
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)