文献类型：期刊文献

英文题名：Experimental and Computational Study on the Intramolecular Hydrogen Atom Transfer Reactions of Maleimide-Based Enediynes After Cycloaromatization

作者：Zhang, Mengsi[1];Lu, Haotian[1];Li, Baojun[1];Ma, Hailong[1];Wang, Wenbo[1];Cheng, Xiaoyu[1];Ding, Yun[1];Hu, Aiguo[1]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai Key Lab Adv Polymer Mat, Shanghai 200237, Peoples R China

年份：2021

卷号：86

期号：2

起止页码：1549

外文期刊名：JOURNAL OF ORGANIC CHEMISTRY

收录：;EI(收录号：20210209762998);WOS:【SCI-EXPANDED(收录号:WOS:000643595200020)】；

基金：Dedicated to the 100th anniversary of Chemistry at Nankai University. The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (21871080 and 21503078), the Fundamental Research Funds for the Central Universities (22221818014), and Shanghai Leading Academic Discipline Project (B502). A.H. thanks the "Eastern Scholar Professorship" support from Shanghai local government.

语种：英文

外文关键词：Chemical bonds - Hydrogen - Reaction intermediates - Bioactivity - Cyclization - Abstracting - Atoms - Spectroscopic analysis - Computation theory - Hydrocarbons

摘要：The follow-up reaction pathways of the diradical species formed from cycloaromatization of enediynes or enyne-allenes determine their ability of H-abstraction from DNA, significantly affecting their biological activity performance. To gain a deeper understanding of subsequent reaction pathways of the diradical intermediates formed from acyclic enediynes based on maleimide-assisted rearrangement and cycloaromatization (MARACA), a maleimide-based enediyne featuring methylene groups adjacent to the propargyl sites of the terminal alkynes was synthesized through the Sonogashira coupling reaction. Three thermal cyclization products after intramolecular hydrogen atom transfer (HAT) were obtained from the thermolysis experiment and their structures were confirmed by 1D and 2D nuclear magnetic resonance spectroscopic analysis. Density functional theory was employed to analyze the important elementary steps including rearrangement, cycloaromatization, and intramolecular HAT processes toward the formation of the cyclized products, where the low-energy barriers of HAT pathways relative to the formation of diradicals from cycloaromatization were successfully identified. Overall, the HAT processes to consume diradicals intramolecularly have become competitive with that of intermolecular H-abstraction, implying that the DNA-cleavage ability of enediynes can be further boosted once the HAT processes are halted. This study offers a promising direction for designing novel and potent acyclic enediynes for antitumor applications.