可见光/酶双催化体系催化的烯酮不对称环加成反应及机理研究

Chemistry brings all sorts of convenience to us, but at the meantime it also causes pollution and the huge consumption of energy and raw materials. Thus, nowadays, looking for clean and sustainable energy has become the most important and the most urgent problem. After millions of years of evolution, photosynthesis, especially, its electron or energy transfer path way and method, provides a model for scientists to learn and mimic the nature, and it also becomes a source of inspiration for human to develop and utilize the solar energy. In view of above points, we innovatively propose the study of combining enzymatic catalysis with photoredox catalysis. (1) Design: Using photosensitizer to activate reaction substrates under visible light irradiation; at the same time, using enzyme to control the stereoselectivity of the reaction through asymmetric environment of enzyme active site. (2) Aim: To develop new asymmetric synthesis method. (3) Research contents: Using ketene cycloaddition as a model, to screen and find out the dual catalysis system of enzymatic catalysis and photoredox catalysis with high reactivity and stereoselectivity; furthermore, to apply the developed mothed in the synthesis of a natural product; to explore the catalytic mechanism of the dual catalytic system. (4) Significance: The project, if successfully implemented, would be able to expand the research and application of the enzyme and light catalysis respectively and enrich the types of asymmetric catalysts, organic catalytic models and approaches.

化学给人类带来各种便利的同时也带来了严重的环境污染、巨大的能源和原材料消耗。寻找可持续的洁净能源是当前最重要和最紧迫的科学问题。经过千万年进化几近完美的光合作用，其电子或能量转移的路径和方法为人类学习和模仿自然以开发利用太阳能提供了借鉴。本申请模仿光合作用，创新性地开展可见光催化结合酶催化的双催化体系的研究。（1）设想：光敏剂在可见光激发下活化反应底物，酶在协同催化的同时通过其活性位点的不对称环境控制反应的立体选择性，促使反应高效进行。（2）目标： 发展新的不对称合成方法。（3）研究内容：以烯酮的环加成反应作为模型反应；筛选高反应活性和立体选择性的可见光/酶双催化体系；发展新的不对称合成方法学并应用于天然产物的合成；探索双催化体系的催化机理。（4）意义：本项目的成功实施，将拓展酶催化和光催化各自的研究和应用范围；丰富不对称催化剂的种类和不对称催化反应的类型；发现新的催化模式和新的反应途径。

化学给人类带来各种便利的同时也带来了严重的环境污染、巨大的能源和原材料消耗。寻找可持续的洁净能源是当前最重要和最紧迫的科学问题。经过千万年进化几近完美的光合作用，其电子或能量转移的路径和方法为人类学习和模仿自然以开发利用太阳能提供了借鉴。本申请模仿光合作用，创新性地开展可见光催化结合酶催化的双催化体系的研究。通过四年的研究，我们完成了：1. 首次实现了水解酶的非天然催化活性与可见光催化相结合，并用于对映选择性有机合成，发展了可见光催化/酶催化从2-芳基吲哚直接不对称一锅法合成2,2-二取代吲哚-3-酮的方法，并将此方法应用于天然产物Incargranine B的骨架构建；2. 可见光和酶接力催化策略：通过酶缓慢水解氨基酸酯，达到调控可见光催化脱羧的速率，实现可见光/酶催化的吲哚氨烷基化；3. 酶和光接力催化合成1,3-恶嗪衍生物，通过酶催化的水解反应开启可见光催化脱羧/Mannich/加成/分子内环化反应，发展了一锅化合成1,3-恶嗪衍生物等重要合成方法。