BioChem - DOS

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

Angewandte Chemie. international edition

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

<P><B>Abstract</B></P><P>Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and &omega;&#8208;transaminase (&omega;&#8208;TA) biocatalysts to establish the key stereocentres of these molecules. Several enantiocomplementary IREDs were identified for the synthesis of (<I>R</I>)&#8208; and (<I>S</I>)&#8208;5&#8208;methyl&#8208;6,7&#8208;dihydro&#8208;5<I>H</I>&#8208;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. &omega;&#8208;TA biocatalysts were also successfully employed for the production of enantiopure 1&#8208;(2&#8208;bromophenyl)ethan&#8208;1&#8208;amine, thus enabling an orthogonal route for the installation of chirality into dibenz[c,e]azepine framework.</P>

2017

1433-7851

1521-3773

56

49

pp.15589-15593

10.1002/anie.201708453

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART79143035

biocatalysis; heterocycles; reductases; synthetic methods; transaminases