Development Of DNA Compatibility Reaction Of Forming C-S/C-Se Bond By Oxidation

The C-S/C-Se bond exists in a wide range of natural products,bioactive molecules and drug molecules.The development of methods for the construction of C-S/C-Se bond is an important basis for the discovery of innovative drug seed compounds.In addition,it plays an important role in biochemistry and pharmaceutical chemistry.Therefore,it is of vital to construct C-S/C-Se bonding in a way that is efficient,mild,and broad substrate scope in the synthesis of sulfur/selenium-containing chemical libraries.Such libraries forge the basis for hit screening in pursue of innovative drugs.DNA encoded libraries(DEL)have become powerful tools for hit discovery in innovative drugs development.Compared with conventional high-throughput screening(HTS)technology,DEL featuring rapid synthesis in a limited time,affordable low cost,and huge library capacity,has been incorporated in both industrial and academia for drug R&D.Thus,to develop sulfur/selenium-containing chemical libraries covering broad chemical space and versatile structural diversity is significantly necessary.However,current DNA-compatible constructions of C-S/C-Se bonding require harsh conditions like high temperature,transition metal mediation,or specific substrates mainly aryl halides,hindering its general application in broadening substrate scope and large-scale diverse synthesis.Oxidative coupling strategy assembling simple building blocks(BBs)into complicated structural molecule via oxidations,has been applied in C-S/C-Se bond formation.Herein,in this thesis,oxidative coupling reaction has been developed to construct C-S/C-Se bonds.Firstly,the model reaction condition of DNA-compatible C-S/C-Se formation was optimized by exploration of different oxidants and additives.Drug-like substrate scope was then investigated to find that moderate-to-good conversions were obtained in a large variety of electron-rich aryl compounds such as indoles,pyrazolones,anilines,and benzoic ethers.Follow-up DNA-compatible oxidation of sulfide and selenide into corresponding sulfoxide/selenoxide expands the structural diversity in the chemical libraries.This method was then elucidated for its future application for DEL through the construction of mock library.In conclusion,the strategy,developed in this thesis,enables direct C-S/C-Se construction via oxidative coupling,taking advantages of mild condition,simple protocol,and no pre-functionalization of substrates.Therefore,our method paves the way for C-S/C-Se bond formation in pursue of DNA-compatible reaction expansion.