Bioorthogonal chemistry is widely used in biological systems and has been trialed in patients, attracting a lot of attention in this century. Tetrazine-based bioorthogonal reactions are essential in chemical biology applications, including cellular labeling, live-cell imaging, diagnosis, drug release, and oncotherapy, due to their tunable rapid reaction kinetics and unique fluorogenic characteristics. However, the scope of de novo tetrazine synthesis is restricted due to the limited supply of commercial starting materials. Therefore, derivatization based on tetrazine scaffolds has been used to synthesize various tetrazine derivatives to enhance the applications of tetrazine bioorthogonal reactions. Herein, the recent advances in tetrazine scaffold-based derivatizations, including tetrazine skeletons, aromatic substituents and alkyl substituents of tetrazines, have been summarized. The advantages and limitations of the derivatization methods and applications of the developed tetrazine derivatives in bioorthogonal chemistry have also been highlighted.

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基于四嗪支架的衍生化：四嗪衍生物的合成及其生物医学应用

生物正交化学广泛应用于生物系统，并已在患者身上进行试验，在本世纪引起了广泛关注。基于四嗪的生物正交反应在化学生物学应用中至关重要，包括细胞标记、活细胞成像、诊断、药物释放和肿瘤治疗，因为它们具有可调的快速反应动力学和独特的荧光特性。但是，从头的范围由于商业原料供应有限，四嗪合成受到限制。因此，基于四嗪支架的衍生化已被用于合成各种四嗪衍生物，以增强四嗪生物正交反应的应用。在此，总结了基于四嗪支架的衍生化的最新进展，包括四嗪骨架、芳族取代基和四嗪的烷基取代基。开发的四嗪衍生物在生物正交化学中的衍生方法和应用的优点和局限性也得到了强调。