Enzymatic N-Allylation of Primary and Secondary Amines Using Renewable Cinnamic Acids Enabled by Bacterial Reductive Aminases.
Enzymatic N-Allylation of Primary and Secondary Amines Using Renewable Cinnamic Acids Enabled by Bacterial Reductive Aminases.
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DOI：
10.1021/acssuschemeng.2c01180
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发表时间：
2022-05-23
影响因子：
8.4
通讯作者：
Leys, David
中科院分区：
文献类型：
--
作者：
Aleku, Godwin A.;Titchiner, Gabriel R.;Roberts, George W.;Derrington, Sasha R.;Marshall, James R.;Hollfelder, Florian;Turner, Nicholas J.;Leys, David
关键词：
烯丙基胺是合成许多有价值的含氮有机化合物（包括药物）的通用类前体。酶促烯丙基胺化方法为这些化合物提供了可持续的途径，但通常限于烯丙基伯胺。我们报告了一个生物催化系统的还原N-烯丙基化的伯胺和仲胺，使用生物质衍生肉桂酸。两步一锅法系统包括由羧酸还原酶催化的初始羧酸盐还原步骤，以原位产生相应的α，β-不饱和醛。随后通过细菌还原性氨酶pIR 23或BacRedAm催化醛的还原性胺化以产生相应的烯丙基胺。我们开发了pIR 23，一种原型细菌还原性氨酶，其在催化α，β-不饱和醛与各种胺的形式还原胺化中自给自足，在温和的反应条件下以高达94%的转化率产生广泛的仲胺和叔胺。从制备反应中分离的产物的分析表明，仅发生C=N键的选择性氢化，保留相邻的烯烃部分。该方法代表了用于合成仲烯丙基胺和叔烯丙基胺框架的环境友好和可持续的方法，使用可再生的烯丙基化试剂并避免苛刻的反应条件。系统的选择性确保避免了烷基胺的双烯丙基化和烯烃部分的（过度）还原。开发了一种利用可再生肉桂酸进行伯胺和仲胺N-烯丙基化的生物催化路线。
Allylic amines are a versatile class of synthetic precursors of many valuable nitrogen-containing organic compounds, including pharmaceuticals. Enzymatic allylic amination methods provide a sustainable route to these compounds but are often restricted to allylic primary amines. We report a biocatalytic system for the reductive N-allylation of primary and secondary amines, using biomass-derivable cinnamic acids. The two-step one-pot system comprises an initial carboxylate reduction step catalyzed by a carboxylic acid reductase to generate the corresponding α,β-unsaturated aldehyde in situ. This is followed by reductive amination of the aldehyde catalyzed by a bacterial reductive aminase pIR23 or BacRedAm to yield the corresponding allylic amine. We exploited pIR23, a prototype bacterial reductive aminase, self-sufficient in catalyzing formal reductive amination of α,β-unsaturated aldehydes with various amines, generating a broad range of secondary and tertiary amines accessed in up to 94% conversion under mild reaction conditions. Analysis of products isolated from preparative reactions demonstrated that only selective hydrogenation of the C=N bond had occurred, preserving the adjacent alkene moiety. This process represents an environmentally benign and sustainable approach for the synthesis of secondary and tertiary allylic amine frameworks, using renewable allylating reagents and avoiding harsh reaction conditions. The selectivity of the system ensures that bis-allylation of the alkylamines and (over)reduction of the alkene moiety are avoided. A biocatalytic route for the N-allylation of primary and secondary amines using renewable cinnamic acids has been developed.
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影响因子：
8.4
作者：
Aleku GA;Roberts GW;Titchiner GR;Leys D
通讯作者：
Leys D
影响因子：
4.1
作者：
Gahloth, Deepankar;Aleku, Godwin A.;Leys, David
通讯作者：
Leys, David
影响因子：
5
作者：
AMERY, WK
通讯作者：
AMERY, WK
DOI：
10.1016/0190-9622(90)70288-s
发表时间：
1990-10-01
影响因子：
13.8
作者：
BIRNBAUM, JE
通讯作者：
BIRNBAUM, JE
影响因子：
15
作者：
Evans, PA;Robinson, JE;Nelson, JD
通讯作者：
Nelson, JD