Zhang Fa-Guang, Chen Zhen, Tang Xiaodong, Ma Jun-An
Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Frontiers Science Center for Synthetic Biology (Ministry of Education), and Tianjin Collaborative Innovation Center of Chemical Science & Engineering, Tianjin University, Tianjin 300072, P. R. China.
Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, P. R. China.
Chem Rev. 2021 Dec 8;121(23):14555-14593. doi: 10.1021/acs.chemrev.1c00611. Epub 2021 Sep 29.
Triazines are an important class of six-membered aromatic heterocycles possessing three nitrogen atoms, resulting in three types of regio-isomers: 1,2,4-triazines (-triazines), 1,2,3-triazines (-triazines), and 1,3,5-triazines (-triazines). Notably, the application of triazines as cyclic aza-dienes in inverse electron-demand Diels-Alder (IEDDA) cycloaddition reactions has been established as a unique and powerful method in -heterocycle synthesis, natural product preparation, and bioorthogonal chemistry. In this review, we comprehensively summarize the advances in the construction of these triazines via annulation and ring-expansion reactions, especially emphasizing recent developments and challenges. The synthetic transformations of triazines are focused on IEDDA cycloaddition reactions, which have allowed access to a wide scope of heterocycles, including pyridines, carbolines, azepines, pyridazines, pyrazines, and pyrimidines. The utilization of triazine IEDDA reactions as key steps in natural product synthesis is also discussed. More importantly, a particular attention is paid on the bioorthogonal application of triazines in fast click ligation with various strained alkenes and alkynes, which opens a new opportunity for studying biomolecules in chemical biology.
三嗪是一类重要的含三个氮原子的六元芳香杂环化合物，由此产生三种类型的区域异构体：1,2,4-三嗪（-三嗪）、1,2,3-三嗪（-三嗪）和1,3,5-三嗪（-三嗪）。值得注意的是，三嗪作为环状氮杂二烯在逆电子需求狄尔斯-阿尔德（IEDDA）环加成反应中的应用，已成为-杂环合成、天然产物制备和生物正交化学中一种独特而强大的方法。在本综述中，我们全面总结了通过环化和扩环反应构建这些三嗪的研究进展，特别强调了近期的发展和挑战。三嗪的合成转化主要集中在IEDDA环加成反应上，该反应可用于合成多种杂环化合物，包括吡啶、咔啉、氮杂卓、哒嗪、吡嗪和嘧啶。还讨论了三嗪IEDDA反应在天然产物合成中作为关键步骤的应用。更重要的是，特别关注了三嗪在与各种张力烯烃和炔烃的快速点击连接中的生物正交应用，这为化学生物学中生物分子的研究开辟了新的机会。
