Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation.
Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation.
复制标题
DOI：
10.1038/ncomms8789
复制
发表时间：
2015-07-24
影响因子：
16.6
通讯作者：
Lewis JC
中科院分区：
文献类型：
--
作者：
Srivastava P;Yang H;Ellis-Guardiola K;Lewis JC
通过将合成金属催化剂掺入蛋白质支架中形成的人工金属酶（ArM）有可能赋予化学反应选择性，这是单独使用金属催化剂难以实现的。在这项工作中，我们将炔烃取代的二铑催化剂与含有基因编码的L-4-叠氮基苯丙氨酸残基的脯氨酰寡肽酶共价连接，以产生催化烯烃环丙烷化的ArM。然后使用支架诱变来提高该反应的对映选择性，并且一系列苯乙烯和供体-受体卡宾前体的环丙烷化被接受。 ArM 减少了副产物的形成，包括二铑卡宾中间体与水反应产生的副产物。这表明 ArM 可以提高催化剂的底物特异性，并首次提高金属催化反应的耐水性。鉴于二铑配合物催化反应的多样性，我们预计二铑ArMs将为选择性催化提供许多独特的机会。人工金属酶（ArM）具有提高复杂介质中过渡金属反应活性的潜力。在这里，作者将二铑催化剂与脯氨酰寡肽酶连接起来，创建了一种在水溶液中催化对映选择性烯烃环丙烷化的 ArM。
Artificial metalloenzymes (ArMs) formed by incorporating synthetic metal catalysts into protein scaffolds have the potential to impart to chemical reactions selectivity that would be difficult to achieve using metal catalysts alone. In this work, we covalently link an alkyne-substituted dirhodium catalyst to a prolyl oligopeptidase containing a genetically encoded L-4-azidophenylalanine residue to create an ArM that catalyses olefin cyclopropanation. Scaffold mutagenesis is then used to improve the enantioselectivity of this reaction, and cyclopropanation of a range of styrenes and donor–acceptor carbene precursors were accepted. The ArM reduces the formation of byproducts, including those resulting from the reaction of dirhodium–carbene intermediates with water. This shows that an ArM can improve the substrate specificity of a catalyst and, for the first time, the water tolerance of a metal-catalysed reaction. Given the diversity of reactions catalysed by dirhodium complexes, we anticipate that dirhodium ArMs will provide many unique opportunities for selective catalysis. Artificial metalloenzymes (ArMs) have the potential to improve transition metal reactivity in complex media. Here, the authors link a dirhodium catalyst to a prolyl oligopeptidase to create an ArM that catalyzes enantioselective olefin cyclopropanation in aqueous solution.