Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines
Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines
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DOI：
10.1002/anie.201708453
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发表时间：
2017-12-04
影响因子：
16.6
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
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作者：
France, Scott P.;Aleku, Godwin A.;Turner, Nicholas J.
二苯并[c，e]氮杂环丙烷的生物催化反合成分析强调了亚胺还原酶(IRED)和欧米伽转氨酶(OMEGA-TA)生物催化剂的使用，以建立这些分子的关键立体中心。通过还原母体亚胺合成了具有良好对映体选择性的(R)-和(S)-5-甲基-6，7-二氢-5H-二苯并[c，e]氮杂卓。结晶学证据表明，红外线可能能够与亚胺底物的一个构象结合，从而在还原时直接生成主要产物构象。欧米伽-TA生物催化剂也被成功地用于生产对映体1-(2-溴苯基)乙烷-1-胺，从而使手性安装到二苯并[c，e]氮杂环己烷骨架的正交路线成为可能。
Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and omega-transaminase (omega-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. omega-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.