Biocatalytic Approaches to the Synthesis of Enantiomerically Pure Chiral Amines
Biocatalytic Approaches to the Synthesis of Enantiomerically Pure Chiral Amines
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DOI：
10.1007/s11244-013-0184-1
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发表时间：
2014-03-01
影响因子：
3.6
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
Ghislieri, Diego;Turner, Nicholas J.
对映体纯的手性胺是合成药物和农用化学品的有价值的结构单元。实际上，据估计，目前40%的药物在其结构中含有手性胺组分。手性胺也被广泛用作非对映体盐结晶的拆分剂。制备对映体纯形式的手性胺的挑战之一是开发能够满足对整个范围的伯胺、仲胺和叔胺的需求的具有成本效益和可持续的催化方法。在这篇综述中，我们强调了各种生物催化策略，已开发，特别是那些基于不对称合成或其等效物，因此（即动态动力学拆分，去消旋），其中收率和对映体过量接近100%，可以达到。特别注意的是使用单胺氧化酶（MAO-N）从尼日尔曲霉已被改造的定向进化，以提供一个工具箱的变体，可以产生对映体纯的伯，仲和叔胺。这些MAO-N变体在去外消旋化过程中与非选择性化学还原剂组合。
Enantiomerically pure chiral amines are valuable building blocks for the synthesis of pharmaceutical drugs and agrochemicals. Indeed it is estimated that currently 40 % of pharmaceuticals contain a chiral amine component in their structure. Chiral amines are also widely used as resolving agents for diastereomeric salt crystallization. One of the challenges of preparing chiral amines in enantiomerically pure form is the development of cost-effective and sustainable catalytic methods that are able to address the requirement for the entire range of primary, secondary and tertiary amines. In this review we highlight various biocatalytic strategies that have been developed, particularly those based upon asymmetric synthesis or their equivalent therefore (i.e. dynamic kinetic resolution, deracemisation) in which yields and enantiomeric excesses approaching 100 % can be attained. Particular attention is given to the use of monoamine oxidase (MAO-N) from Aspergillus niger which has been engineered by directed evolution to provide a tool-box of variants which can generate enantiomerically pure primary, secondary and tertiary amines. These MAO-N variants are combined with non-selective chemical reducing agents in deracemisation processes.