Hyperconjugation-Driven Isodesmic Reaction of Indoles and Anilines: Reaction Discovery, Mechanism Study, and Antitumor Application.

Autor: Xiao YQ; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China., Fang KX; State Key Laboratory of Chemical Oncogenomics, Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China., Zhang Z; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China., Zhang C; State Key Laboratory of Chemical Oncogenomics, Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China., Li YJ; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China., Wang BC; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China., Zhang BJ; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China., Jiang YQ; State Key Laboratory of Chemical Oncogenomics, Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China., Zhang M; State Key Laboratory of Chemical Oncogenomics, Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China., Tan Y; State Key Laboratory of Chemical Oncogenomics, Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China., Xiao WJ; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China.; Wuhan Institute of Photochemistry and Technology, 430082, Wuhan, Hubei, P. R. China., Lu LQ; Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, 430079, Wuhan, Hubei, China.; Wuhan Institute of Photochemistry and Technology, 430082, Wuhan, Hubei, P. R. China.; State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, 730000, Lanzhou, P. R. China.; School of Chemistry and Chemical Engineering, Henan Normal University, 453007, Xinxiang, Henan, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Aug 23, pp. e202408426. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1002/anie.202408426
Abstrakt: Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: