提升药物开发效率的策略：电催化不对称苄基C-H的后期多官能团化

如何提升药物研发的效率和降低药物的成本是药企面临的主要挑战。后期官能团化（LSF）能够快速多样地衍生新先导物、大大缩短现有药物的合成路线、降低药物的生产成本、提高药物研发的效率和药物生产的绿色程度。但目前LSF的现状：对映选择性的C-H官能团化方法欠缺；现有的C-H官能团化条件不温和及环境不友好，候选药物耐受性较差，不适合药物多步合成的后期使用。.本项目针对苄基C-H键，采用过渡金属与手性配体原位生成的手性金属配合物协同电催化作为催化系统，用电替代有毒易爆的氧化剂，阳极氧化苄基化合物成为苄基自由基，在过渡金属配合物催化下实现苄基C-H不对称官能团化，阳极氧化低价金属回到高价实现催化剂循环。目的是构建操作简单、绿色和高效的苄基C-H键的不对称多官能团化LSF平台，突破药物研发效率低和绿色生产水平低的技术瓶颈，提高药物研发及生产效率，减低药物成本，为探索更广泛的LSF方法提供技术和理论储备。

How to improve the efficiency of drug research and development and reduce the cost of drug production is a major challenge for pharmaceutical companies. Late stage functionalization (LSF) can rapidly and diversely derivate new leads, significantly shorten the synthesis route of drugs, reduce the cost of drugs, improve the efficiency of drug research and development, and increase the greenness of drug production. However, the current challenges of LSF is as follows: (1) lack of enantioselective C-H functionalization methods; (2) The existing conditions of C-H functionalization are not mild and environmentally unfriendly, and the tolerance of drug candidates is poor, which is not suitable for the late use of multi-step drug synthesis. .For the benzyl C-H bond, this project utilizes electrocatalysis and chiral metal complex generated in situ by transition metal and chiral ligand as a catalytic system. Electricity is used to replace toxic and explosive oxidants, anodic oxidation of benzyl compounds generate benzyl radical, and benzyl C-H asymmetric functionalization is achieved under transition metal complexes catalysis. Then anodic oxidation of metal achieves catalyst cycle. The aim is to construct a simple, green, efficient, and asymmetric LSF platform, to break through the technical bottleneck of low efficiency of drug research and development and low green production level, to improve drug research and development and production efficiency, to reduce drug cost, and to provide technical and theoretical reserve for exploring a broader LSF method.