英国利物浦大学Bower, John F.团队报道了定向烯醇化策略能够在合成复杂氨基酸的过程中，无副产物地构建连续的立体中心。相关研究成果发表在2024年4月2日出版的《自然—化学》。

同手性α-氨基酸作为手性催化剂合成的关键亚基或合成生物学的构建块，在药物设计中被广泛使用。已经开发了许多合成方法，通过控制α-立体中心的安装来获得罕见或非天然的变体。相比之下，尽管它们很重要，但具有β-立体中心的α-氨基酸更难合成。

该文中，研究人员展示了一种铱催化的方案，该方案能够使简单的烯烃和甘氨酸衍生物的直接上转化，以产生具有异常水平的区域和立体控制的β-取代的α-氨基酸。该方法利用甘氨酸衍生的N–H单元的天然导向能力，来促进Ir催化的相邻羰基的烯醇化。所得的立体定义的烯醇化物与苯乙烯或α-烯烃交联，形成两个连续的立体中心。

该过程具有非常高水平的区域和立体控制，并具有完全的原子经济性。从更广泛的角度来看，该反应设计为羰基化合物的直接立体控制α-烷基化，提供了一种独特的定向基团控制策略，并为合成具有挑战性的连续立体中心提供了一个强大的方法。

附：英文原文

Title: A directed enolization strategy enables by-product-free construction of contiguous stereocentres en route to complex amino acids

Author: Hong, Fenglin, Aldhous, Timothy P., Kemmitt, Paul D., Bower, John F.

Issue&Volume: 2024-04-02

Abstract: Homochiral α-amino acids are widely used in pharmaceutical design as key subunits in chiral catalyst synthesis or as building blocks in synthetic biology. Many synthetic methods have been developed to access rare or unnatural variants by controlling the installation of the α-stereocentre. By contrast, and despite their importance, α-amino acids possessing β-stereocentres are much harder to synthesize. Here we demonstrate an iridium-catalysed protocol that allows the direct upconversion of simple alkenes and glycine derivatives to give β-substituted α-amino acids with exceptional levels of regio- and stereocontrol. Our method exploits the native directing ability of a glycine-derived N–H unit to facilitate Ir-catalysed enolization of the adjacent carbonyl. The resulting stereodefined enolate cross-couples with a styrene or α-olefin to install two contiguous stereocentres. The process offers very high levels of regio- and stereocontrol and occurs with complete atom economy. In broader terms, our reaction design offers a unique directing-group-controlled strategy for the direct stereocontrolled α-alkylation of carbonyl compounds, and provides a powerful approach for the synthesis of challenging contiguous stereocentres.

DOI: 10.1038/s41557-024-01473-5

Source: https://www.nature.com/articles/s41557-024-01473-5