新型重氮试剂的制备、反应及其在生物偶联中的应用研究

Diazo compounds are very important class of reagents and intermediates for organic synthesis, and have been widely applied in organic synthesis, medicinal chemistry, biological chemistry as well as material sciences. Consequently, we are planning to research on the chemistry of alpha-diazo imidates and alpha-diazo imidothioates, a novel class of diazo compounds. We will focus our attentions on the preparation and transformations of these compounds, including diazo nitrogen retaining reactions, olefinations, arylations, and transition-metal-catalyzed C-H bond insertions, formal cycloadditions, the formations of Ylides, C-H bond activation/annulations as well as C-H bond functionalizations through a metal carbene intermediate, which are believed to lead to the development of novel approaches for the syntheses of diverse heterocyclic compounds (especially, the triazole-, pyrazole-, indole-, isoindole-, and isoquinoline-ring systems) and some nonnative amino acids. The new reactions between alpha-diazo imidates and primary amines are also planned to developed as a novel bioconjugation reaction for the conjugation of chemical reporter group (e.g., fluorophore tags, drugs and nitroxyl labels) with bimolecular (e.g., peptides and proteins). It is anticipated that these studies could provide a novel class of diazo reagents and methodologies for the synthetic chemistry and biological chemistry.

重氮化合物是一大类非常重要有机合成试剂和中间体, 在合成化学、药物化学、化学生物学、材料化学等领域具有广泛应用。本项目拟以alpha-重氮（硫代）酯亚胺——一类新的重氮化合物的化学为目标，系统研究其制备方法和化学转化，包括重氮保留反应，烯基化和芳基化反应，经由金属卡宾的C-H插入反应、形式环加成反应、形成叶立德的反应、C-H活化/环化反应、C-H键官能团化等，以及相关的串联反应，这些转化可望发展成为多种氮杂环化合物（如三氮唑、吡唑、吡咯、吲哚、异吲哚和异喹啉的衍生物）和一些非天然氨基酸等重要有机化合物的合成新方法。此外，本项目还计划将上述研究中的三氮唑合成新方法用作多肽和蛋白质分子与特异化学报告基团（如荧光团、亲和标记和氮氧自由基标记）的生物偶联反应，以期发展一种新的生物偶联方法。本项目的研究将有望为合成化学和化学生物学提供一类新试剂、一些新反应和新方法。