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不对称铜催化的有机金属试剂共轭加成在天然产物和药物合成中的应用。

Asymmetric copper-catalyzed conjugate additions of organometallic reagents in the syntheses of natural compounds and pharmaceuticals.

机构信息

Comenius University in Bratislava, Faculty of Natural Sciences, Department of Organic Chemistry, Mlynská dolina, Ilkovičova 6, SK-84215, Bratislava, Slovakia.

出版信息

Org Biomol Chem. 2020 May 27;18(20):3780-3796. doi: 10.1039/d0ob00278j.

Abstract

Access to enantiopure complex molecular structures is crucial for the development of new drugs as well as agents used in crop-protection. In this regard, numerous asymmetric methods have been established. Copper-catalyzed 1,4-additions of organometallic reagents are robust C-C bond formation strategies applicable in a wide range of circumstances. This review analyses the syntheses of natural products and pharmaceutical agents, which rely on the application of asymmetric Cu-catalyzed conjugate additions of various organometallic reagents. A wide range of available organometallics, e.g. dialkylzinc, trialkylaluminum, Grignard, and organozirconium, can now be used in conjugate additions to address various synthetic challenges present in targeted natural compounds. Furthermore, efficient catalysts allow high levels of stereofidelity over a diverse array of starting Michael acceptors.

摘要

获得对映纯复杂分子结构对于开发新药以及用于作物保护的试剂至关重要。在这方面,已经建立了许多不对称方法。铜催化的有机金属试剂的 1,4-加成是适用于广泛情况的稳健的 C-C 键形成策略。这篇综述分析了依赖于各种有机金属试剂的不对称 Cu 催化共轭加成的天然产物和药物试剂的合成。现在可以使用广泛的有机金属试剂,例如二烷基锌、三烷基铝、格氏试剂和有机锆,来进行共轭加成,以解决目标天然化合物中存在的各种合成挑战。此外,高效的催化剂允许在各种起始迈克尔受体上实现高水平的立体保真度。

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