Abstract：
Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage is of great importance for expanding the click chemistry toolbox. We report the first selenium-nitrogen exchange (SeNEx) click reaction between benzoselenazolones and terminal alkynes (Se-N to Se-C), which is inspired by the biochemical SeNEx between Ebselen and cysteine (Cys) residue (Se-N to Se-S). The formed selenoalkyne connection is readily elaborated, thus endowing this chemistry with multidimensional molecular diversity. Besides, this reaction is modular, predictable, and high-yielding, features fast kinetics (k2≥14.43 M-1 s-1), excellent functional group compatibility, and works well at miniaturization (nanomole-scale), opening up many interesting opportunities for organo-Se synthesis and bioconjugation, as exemplified by sequential click chemistry (coupled with ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) and sulfur-fluoride exchange (SuFEx)), selenomacrocycle synthesis, nanomole-scale synthesis of Se-containing natural product library and DNA-encoded library (DEL), late-stage peptide modification and ligation, and multiple functionalization of proteins. These results indicated that SeNEx is a useful strategy for new click chemistry developments, and the established SeNEx chemistry will serve as a transformative platform in multidisciplinary fields such as synthetic chemistry, material science, chemical biology, medical chemistry, and drug discovery.
摘要：
点击化学是快速发现功能的强大分子组装策略。具有新的连接链接的点击反应的开发对于扩展点击化学工具箱非常重要。我们报告了苯并硒唑酮与末端炔烃（Se-N至Se-C）之间的第一个硒氮交换（SeNex）点击反应，其灵感来自Ebselen和半胱氨酸（Cys）残基（Se-N至Se-S）之间的生化SeNex。形成的硒炔烃连接很容易阐述，从而赋予这种化学多维分子多样性。此外,这种反应是模块化的，可预测的,和高产，具有快速动力学(k2≥14.43M-1s-1)，优异的官能团相容性，并且在小型化（纳摩尔尺度）方面效果很好，为有机硒合成和生物缀合开辟了许多有趣的机会，如顺序点击化学（与钌催化的叠氮化物-炔环加成（RuAAC）和硫-氟化物交换（SuFEx）偶联）硒代碳氢合成，含硒天然产物库和DNA编码库(DEL)的纳米摩尔尺度合成,晚期肽修饰和连接，和蛋白质的多重功能化。这些结果表明，SeNEx是新的点击化学开发的有用策略，建立的SeNEx化学将成为合成化学等多学科领域的变革性平台，材料科学,化学生物学,医学化学,和药物发现。
