CuBr-promoted domino Biginelli reaction for the diastereoselective synthesis of bridged polyheterocycles:Mechanism studies and in vitro anti-tumor activities

作     者：Mengting Zeng Ying Xue Yunan Qin Fen Peng Quan Li Ming-Hua Zeng Mengting Zeng;Ying Xue;Yunan Qin;Fen Peng;Quan Li;Ming-Hua Zeng

作者机构：Hubei Collaborative Innovation Center for Advanced Organic Chemical MaterialsMinistry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional MoleculesCollege of Chemistry and Chemical EngineeringHubei UniversityWuhan 430062China Sichuan Center for Disease Control and PreventionChengdu 610041China Key Laboratory for the Chemistry and Molecular Engineering of Medicinal ResourcesSchool of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541004China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2022年第33卷第11期

页      面：4891-4895页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.21901067,22171075) Starting Grant from the Ministry of Human Resource and Social Security of China(Q.L.) the NSFC of Guangxi Province(Nos.91122032,2017GXNSFDA198040) the BAGUI talent program(No.2019AC26001) 

主　　题：Multicomponent reaction Domino reaction Biginelli reaction Bridged polyheterocycles Reaction mechanism Anti-tumor activities 

摘      要：The low-cost CuBr-promoted domino Biginelli reaction among readily available ketones,salicylaldehyde derivatives and 3-amino-1,2,4-triazole was studied under solvothermal conditions,giving the novel bridged polyheterocycles bearing two or three stereocenters depending on the starting *** multicomponent reaction proceeded with high diastereoselectivity(dr20:1)based on a combined~1 H NMR,crystallographic and supercritical fluid chromatographic(SFC)analysis of the ***-dependent high-resolution mass spectrometry(HRMS)was performed to track the reaction process,and several key intermediates were identified,leading to the drawing of a plausible reaction *** functional theory(DFT)calculation was supplemented,and two reaction pathways were ***,in vitro antitumor activity was evaluated using HeLa and HepG2 cell lines,and two of these polyheterocycles demonstrated promising activities against HepG2 cells with EC50 down to 10μmol/***,ESI-MS/MS studies on all the polyheterocycles suggest a common fragmentation pathway(loss of one molecule of amino-triazole)they shared,providing the first-hand fragmentation rules for future rapid structural identification of *** multicomponent domino reaction presented here may offer prospects for future design of more efficient strategies to access medicinally important bridged polyheterocycles.