Biocatalytic Routes to Enantiomerically Enriched Dibenz[ c , e ]azepines
Biocatalytic Routes to Enantiomerically Enriched Dibenz[ c , e ]azepines
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富含对映体的二苯并[c,e]氮杂卓类化合物的生物催化路线
DOI：
10.1002/ange.201708453
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发表时间：
2017
影响因子：
--
通讯作者：
France S
中科院分区：
文献类型：
--
作者：
France S
二苯并[c，e]氮杂卓的生物催化逆合成分析强调了亚胺还原酶（IRED）和ω-转氨酶（ω-TA）生物催化剂的使用，以建立这些分子的关键立体中心。通过还原母体亚胺，确定了几种对映互补的IRED用于合成（R）-和（S）-5-甲基-6，7-二氢-5H-二苯并[c，e]氮杂卓，具有良好的对映选择性。晶体学证据表明，IRED可能能够结合亚胺底物的一种构象异构体，使得在还原时直接生成主要产物构象异构体。ω-TA生物催化剂也被成功地用于生产对映体纯的1-（2-溴苯基）乙烷-1-胺，从而实现了将手性安装到二苯并[c，e]氮杂卓框架中的正交路线。
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.