Enzymatic enantioselective decarboxylative protonation of heteroaryl malonates.
Enzymatic enantioselective decarboxylative protonation of heteroaryl malonates.
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DOI：
10.1002/chem.201406014
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发表时间：
2015-04-20
期刊：
影响因子：
--
通讯作者：
Micklefield J
中科院分区：
文献类型：
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作者：
Lewin R;Goodall M;Thompson ML;Leigh J;Breuer M;Baldenius K;Micklefield J
芳基/烯基丙二酸脱羧酶（AMDase）催化一系列二取代丙二酸的对映选择性脱羧质子化（EDP），以产生作为有价值的合成中间体的纯手性羧酸。AMDase与迄今为止开发的非酶促EDP方法相比具有许多优点，包括更高的对映体选择性和更环保的反应条件。在本报告中，AMDase和工程变体已用于从容易获得的α-羟基丙二酸酯生产一系列对映体富集的杂芳族α-羟基羧酸，包括药物前体。本文所述的酶促方法代表了对已用于生产类似化合物的现有合成化学方法的改进。这些新的底物的结构特征和动力学与它们的酶促脱羧的关系进行了探索，这提供了进一步的了解AMDase的机制。
The enzyme aryl/alkenyl malonate decarboxylase (AMDase) catalyses the enantioselective decarboxylative protonation (EDP) of a range of disubstituted malonic acids to give homochiral carboxylic acids that are valuable synthetic intermediates. AMDase exhibits a number of advantages over the non-enzymatic EDP methods developed to date including higher enantioselectivity and more environmentally benign reaction conditions. In this report, AMDase and engineered variants have been used to produce a range of enantioenriched heteroaromatic α-hydroxycarboxylic acids, including pharmaceutical precursors, from readily accessible α-hydroxymalonates. The enzymatic method described here represents an improvement upon existing synthetic chemistry methods that have been used to produce similar compounds. The relationship between the structural features of these new substrates and the kinetics associated with their enzymatic decarboxylation is explored, which offers further insight into the mechanism of AMDase.