Enantioselective Synthesis of N–N Indole-Pyrrole Atropisomers via Palladium/Chiral Phosphonic Acid Relay Catalysis

IF 13.1 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2025-07-09 DOI:10.1021/acscatal.5c02849

Dayuan Wang, Jiayi Zong, Boxuan Zhang, Jiahao Wang, Bowen Wang, Huri Piao, Dang Cheng, Jinfei Lin, Zhiran Ju, Miaolin Ke, Fener Chen

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引用次数: 0

Abstract

N–N atropisomers have emerged as indispensable structural motifs in natural products, medicinal chemistry, and asymmetric catalysis due to their unique stereochemical properties. Herein, we introduce an innovative synthetic methodology for the enantioselective construction of N–N indole-pyrrole atropisomers through palladium/chiral phosphonic acid (CPA) relay catalysis. This process involves allylic alkylation, condensation, and dehydration between vinyl methylene cyclic carbonates and N-amino-indoles, enabling the efficient synthesis of structurally diverse N–N atropisomers with excellent yields (up to 92%) and exceptional enantiocontrol (up to 99% ee). Furthermore, biological evaluation revealed that compounds 3ta, 3sa, 3ca, 3bd, and 3bi demonstrate potent anti-inflammatory activity, significantly inhibiting nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages.

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钯/手性膦酸接力催化对映选择性合成N-N吲哚-吡咯二聚体

由于其独特的立体化学性质，N-N对映体已成为天然产物、药物化学和不对称催化中不可缺少的结构基序。本文介绍了一种新颖的钯/手性膦酸（CPA）接力催化对映选择性构建N-N吲哚-吡咯二聚体的合成方法。该工艺包括乙烯基亚甲基环碳酸酯和n -氨基吲哚之间的烯丙基烷基化，缩合和脱水，从而有效合成具有优异收率（高达92%）和优异的对映体控制（高达99% ee）的结构多样的N-N反旋体。此外，生物学评价显示化合物3ta、3sa、3ca、3bd和3bi具有有效的抗炎活性，显著抑制lps刺激的RAW264.7巨噬细胞中一氧化氮（NO）的产生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.