生物活性分子导向的手性氮杂环骨架的立体选择性合成

本课题着眼于发展新的立体选择性方法，高效构建广泛存在于生物活性分子中的氮杂环骨架。将详细研究新的手性催化剂体系和不对称反应，主要包括设计和合成一系列手性双磷酸催化剂，通过调节连结体的类型改变分子内氢键的强度，实现双磷酸催化活性的调控，并研究其催化的1,3-偶极环加成反应、Povarov反应和Pictet-Spengler反应；设计和合成手性双内盐碱催化剂，研究其催化的3-取代吲哚参与的不对称加成反应；设计过渡金属/手性磷酸和Lewis酸/手性磷酸联合催化剂体系，研究它们协同和接力催化的不对称多组分和串联反应，用于简洁构建结构复杂的手性含氮杂环。利用发展的高效构建杂环骨架的新方法，研究简洁合成生物碱如Spirotryprostatin、(+)-Pumiliotoxin C、Flustramine B、Gliocladin C等的新路线。

The project will be focused on the development of new stereoselective methods to efficiently build up chiral nitrogeneous heterocyclic skeletons that are prevalently present in bioactive molecules. New chiral catalyst systems and asymmetric transformations will be intensely investigated. As such, a variety of bis-phosphoric acids bearing different linkers will be synthesized. By tuning the linker, the catalytic efficiency and stereocontrolling ability will be modulated for a number of asymmetric transformations, including 1,3-dipolar cycloaddition, Povarov reaction, and Pictect-Spengler reaction as well. New chiral bis-betaine bases will be designed and prepared for nucleophilic addition reactions of 3-substituted oxindoles. Transition metal/Bronsted acid and Lewis acid/Bronsted acid binary systems will be designed for either cooperative or relay catalytic cascade reactions. On the basis of the synthetic methods developed, the concise total synthesis of various bioactive alkaloids such as Spirotryprostatin, (+)-Pumiliotoxin C, Flustramine B,Gliocladin C, and Communesin will be accomplished.