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Programmable late-stage C−H bond functionalization enabled by integration of enzymes with chemocatalysis
Nature Catalysis ( IF 37.8 ) Pub Date : 2021-04-29 , DOI: 10.1038/s41929-021-00603-3
Elliott J. Craven , Jonathan Latham , Sarah A. Shepherd , Imtiaz Khan , Alba Diaz-Rodriguez , Michael F. Greaney , Jason Micklefield

New chemo- and biocatalytic methodology is important for the future sustainable synthesis of essential molecules. Transition metal catalysis enables the late-stage C−H functionalization of some complex molecular scaffolds, providing rapid routes to valuable products, although this is largely dependent on the availability of electronically or sterically predisposed C−H bonds for selective metalation, leaving certain regioselectivities inaccessible. Unlike metal chemocatalysis, enzymes can catalyse C−H bond functionalization, discriminating between near-identical, non-activated C−H bonds, delivering products with exquisite regioselectivity. However, enzymes typically provide access to fewer functionalities than more divergent chemocatalysis. Here we report programmable, regioselective C−H bond functionalization methodologies for the installation of versatile nitrile, amide and carboxylic acid moieties through integration of halogenase enzymes with palladium-catalysed cyanation and subsequent incorporation of nitrile hydratase or nitrilase enzymes. Using two- or three-component chemobiocatalytic systems, the regioselective synthesis of complex target molecules, including pharmaceuticals, can be achieved in a one-pot process operable on a gram scale.



中文翻译:

通过酶与化学催化的整合实现可编程的后期 C-H 键功能化

新的化学和生物催化方法对于未来可持续合成基本分子很重要。过渡金属催化能够实现一些复杂分子支架的后期 C-H 官能化,为有价值的产品提供快速途径,尽管这在很大程度上取决于用于选择性金属化的电子或空间预置的 C-H 键的可用性,使得某些区域选择性无法获得. 与金属化学催化不同,酶可以催化 C-H 键功能化,区分几乎相同的非活化 C-H 键,从而提供具有精细区域选择性的产品。然而,与更多不同的化学催化相比,酶通常提供更少的功能。在这里我们报告可编程,通过将卤化酶与钯催化的氰化结合并随后掺入腈水合酶或腈水解酶来安装多功能腈、酰胺和羧酸部分的区域选择性 C-H 键功能化方法。使用两组分或三组分化学生物催化系统,可以在克级可操作的一锅法中实现包括药物在内的复杂靶分子的区域选择性合成。

更新日期:2021-04-29
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