发展高效的合成方法是现代有机合成化学研究的重要任务之一。本申请拟通过酰硅化合物的布鲁克（Brook）重排介导的连续反应，实现对官能化的β-氨基-α-季碳羟基酯结构的高效合成；并探索将该合成方法学应用于天然产物pactamycin的合成中。通过各种官能化的金属试剂作为亲核试剂，对α-酰硅酯加成引发Brook重排，再以各种官能团取代的叔丁基亚磺酰（tBS）亚胺对重排所得的活泼中间体进行捕捉，构筑手性β-氨基-α-季碳羟基酯。通过上述研究，明确不同金属试剂对反应的化学选择性和立体选择性的影响规律，进而指导对反应产出的控制。在此基础上，选择合适的金属试剂和叔丁基亚磺酰亚胺，以上述反应方法学构建pactamycin中的β-氨基-α-季碳羟基结构片段，并最终实现该天然产物的化学全合成。pactamycin作为已知的官能团密集程度最高的氨基环戊醇结构的天然产物，其全合成研究具有重要的学术价值。

Development of efficient synthetic methods is one of the main tasks for modern organic synthetic chemistry. This proposal focuses on the efficient synthesis of chiral multi-functionalized β-amino-α-tertiary hydroxyl esters via Brook rearrangement-mediated cascade reactions of acylsilanes and its application in the total synthesis of natural product of pactamycin. The nucleophilic attack of organometallic reagents to silyl glyoxylates triggers Brook rearrangement, followed by in-situ trapping of the reactive intermediates generated from the rearrangement by N-tert-butanesulfinyl (tBS) imines, resulting in the construction of chiral β-amino-α-tertiary hydroxyl esters. Through the studies on this topic we anticipate clarifying the effects of organometallic reagents (with different metal counterions) on the chemoselectivity and stereoselectivity of this cascade transformation, which will serve as a useful guide for controling the reaction outcomes. Base on the studies mentioned above, suitable substrates of organometallic reagents and N-tert-butanesulfinyl imines will be subjected to the cascade reaction to construct the β-amino-α-tertiary hydroxyl skeleton of pactamycin, and subsequent transformations will furnish its total synthesis. Pactamycin is the most densely functionalized naturally occurring aminocyclopentitol and the studies toward its total synthesis have great academic values. Meanwhile, the development of the cascade methodology will undoubtedly enrich the synthetic toolbox of chiral β-amino-α-tertiary hydroxyl esters.