催化串联反应高效构筑天然产物与药物分子骨架

紫杉醇、青蒿素等天然产物作为药物分子的例子不胜枚举，但很多复杂天然产物合成的路线长，不易规模化生产；为获得这些化合物，有些仍需大面积种植而占用耕地，有的植物因过度采伐而濒临灭绝。发展更加简洁高效、可放大生产的天然药物分子合成路线成为目前研究的当务之急。另外，在有机合成中使用保护与脱保护，除步骤不经济外，易造成环境负担，发展更加绿色、简洁的合成方法迫在眉睫。天然产物和药物分子骨架的构筑是其合成的核心和关键步骤。本项目拟从三个方面开展研究：（1）设计和发展新的涉及金属、有机小分子和可见光催化串联反应策略，发展一批新的串联反应，将其应用到构筑天然产物和药物分子关键骨架中。（2）以构筑天然产物或药物分子骨架为导向，设计和合成新的手性光催化剂，发展不对称可见光催化的新反应和新方法。（3）设计新的过渡金属串联反应将其应用到异吲哚酮和异喹啉酮，发展2-甲叉基苯并氮杂环丁烷为合成子的化学并应用于杂环合成。

Examples that paclitaxel, artemisinin and other natural products are used as drug molecules are too numerous to mention, but the synthesis route of many complex natural product is long, and not easy to large-scale produce. In order to obtain these compounds, some of them still need to occupy cultivated land for widespread planting, and some are on the verge of extinction due to over harvesting. To develop more compact and efficient synthesis route that is befitting for production scale has become an urgent affairs of current research. In addition, the use of protection and deprotection in organic synthesis is not economic in steps and easy to cause the much burden on the environment. Therefore, it is extremely urgent to develop more green and concise synthesis method. The construction of natural products and drug molecular skeleton is the core of synthesis and the key step of synthesis of these compounds. This project intends to carry out this study from the following three aspects: (1) we image to design new strategy of tandem reactions involving transition-metal catalysis, organocatalysis and visible-light photocatalysis, develop a number of new asymmetric cascade reactions, and build key skeleton of natural products and drug molecules with those reactions. (2) To construct key skeleton of natural products and drug molecules, we expect to design and synthesize a series of new chiral photocatalysts, and apply them to some asymmetric photocatalytic reactions. (3) We plan to design kinds of transition-metal catalytic cascade reactions and apply them to the synthesis of isoindolone and isoquinolone derivatives, and develop 2-methylene phenyl azetidine for synthon and apply it to synthesis of heterocyclic compounds.