手性物质的 “精准、高效”获得已制约着手性科学的快速发展，为解决目前的难题，本项目拟先设计和合成多个系列具有我国自主知识产权的氮杂螺环骨架衍生的有机小分子催化剂和手性配体，探索它们在新颖的不对称反应中的催化作用和机制，获取不同结构、功能迥异的手性产物；在此基础上，运用上述发展的新不对称反应作为关键步骤，实现两个临床手性药物ET-743和羟可待酮及一些具有生物活性的天然产物的高效不对称全合成，为这些药物、天然产物及其类似物的高效获得增添新合成策略和方法。.该项目充分体现了“新型手性催化剂与配体的设计合成和反应研究”与“天然产物不对称全合成”的高度融合。项目的实施将对新型手性催化剂的设计、合成及新不对称催化反应的发现，丰富和促进不对称合成及手性化学研究具有重要的学术意义；同时，为临床药物和天然产物的高效精准合成、生物活性及构效关系研究、新的先导手性化合物的发现奠定一定的科学和物质基础。

Access to chiral compounds in a highly efficient and precise manner plays a central role in the development of science of chirality. With an aim to tackle the state-of-the-art challenges, this project is designed to synthesize a range of spiropyrrolidine-derived organocatalysts and ligands with indigenous innovation, explore the catalytic capability of these catalysts in asymmetric reactions, prepare structurally-diverse enantiopure compounds, and investigate the mechanism of these catalytic reactions. Moreover, application of these asymmetric transformations as key steps for the total synthesis of ET-743, oxycodone, and other biologically active natural products would enable the preparation of these pharmaceuticals and active molecules or their derivatives with novel strategies. .The combination of “synthetic methodology development based on the design of novel catalysts and ligands” and “total synthesis of natural product” is highly appreciated in this project, which will have profound academic value in novel chiral catalyst design, development of enantioselective reactions, asymmetric synthesis, and chemistry of chirality. Additionally, the highly efficient total synthesis of related natural molecules and pharmaceuticals will provide a material basis for relevant studies on biological activity and structure-activity relationship.