基于金属导向的自组装金属-酶超分子不对称催化构建C-C键及机理研究

Metal-enzyme supermolecule is a common phenomenon in nature, which is responsible for catalyzing important biological processes, such as photosynthesis, respiration, water oxidation, molecular oxygen reduction and nitrogen fixation. The research of self assembled metal-enzyme supermolecule as catalysts is at its early stage. And the construction of asymmetric C-C bond is the eternal theme of organic chemistry. The development of novel catalysts for the formation of C-C bond is still an important research topic in organic synthesis. The goal of the proposal is to develop new self assembled metal-enzyme supermolecules as catalysts for the construction of asymmetric C-C bond.The following sections are going to be discussed in this project: Choose the typical model reactions of construction of C-C bond; Self-assemble supramolecules as catalysts; High-throughput screen self-assembled metal-enzyme supramolecular catalysts using the model reactions; Select the catalysts with high reactivity and stereoselectivity for further investigation; Develop the methodology for constructing asymmetric C-C bond; Explore the catalytic mechanism of supramolecular catalysts. The aims of this project: (1)To establish the methodology of construction of asymmetric C-C bond catalyzed by self assembled metal-enzyme supramolecular catalysts; (2)To reveal the mechanisms of metal-enzyme supramolecular catalysts; (3)To expand the scope of application of enzymes and supramolecular chemistry; (4)To increase the novel types of asymmetric catalysts for organic synthesis.

金属-酶超分子是自然界的普遍现象，在生物体内负责催化重要的生物过程，如光合作用、呼吸作用、水氧化、分子氧还原和固氮作用。然而,自组装金属-酶超分子用作有机合成催化剂的研究才刚刚起步;不对称C-C键的构建是有机合成永恒的主题，发展新型的构建不对称C-C键的催化剂仍是当前有机合成的主旋律。本项目拟以不对称C-C键的构建为目标，开展金属导向的酶自组装超分子催化剂的研究。项目拟首先建立构建C-C键的模型反应，并以其作为评价超分子催化剂的标准；金属导向的酶超分子的自组装；基于评价标准的高通量筛选金属-酶超分子催化剂；催化剂的优化、结构特性及自组装机理的研究；不对称反应研究；进而探索超分子催化剂的催化机理。本项目的研究旨在建立金属导向的自组装金属-酶超分子作为催化剂构建不对称C-C键的方法学；揭示金属-酶超分子催化剂的催化机理；拓展酶的用途和超分子化学的研究范围，丰富新的不对称催化剂的种类。

本项目开展了金属/酶自组装超分子催化剂的研究以不对称构建C-C 键。项目首先确立了构建C-C 键的各类模型反应，并以其筛选金属-酶超分子催化剂对各类模型反应的催化效果，筛选出下列三类催化体系：.1.金属钌配合物Ru(bpy)3Cl2与南极假丝酵母脂肪酶B共同接力催化吲哚的胺烷基化；.2. 金属钌配合物Ru(bpy)3Cl2与南极假丝酵母脂肪酶B联合催化一锅法合成1,3-恶嗪衍生物；.3. 金属钌配合物Ru(bpy)3Cl2与小麦胚脂肪酶催化2-芳基吲哚直接对映选择性合成2,2-二取代吲哚-3-酮。.进而开展了催化剂的优化、结构特性、不对称反应及机理探索的研究。本项目报道了水解酶的非天然催化活性与可见光催化相结合用于对映选择性有机合成的第一个实例，该反应不需要任何辅因子，体系简单易行。本项目发展了金属/酶作为催化剂构建不对称C-C 键的方法学；拓展了酶的用途和超分子化学的研究范围，丰富了新的不对称催化剂的种类。.完成SCI论文35篇，其中影响因子大于5的论文10篇，包括Angewandte Chemie International Edition一篇；申请专利3件，获授权2件；期间获重庆市自然科学奖二等奖（本人排名第一）。