Amidoglycosylation Reactions of Glycal Metallanitrenes

描述(由申请人提供)：金属催化的分子内氮原子传递将被开发为一种合成广泛的2-氨基糖骨架的方法，包括几丁质酶抑制剂allsamidin的双糖部分。将优化条件，将甘氨酸酯转化为相应的金属酰基腈，启动氮插入到富含电子的甘氨酸烯中，然后与最少的糖基受体进行原位糖基化反应。整个氨基糖基化过程将在新的C-2-N连接以及异构体中心提供具有高立体选择性的2-氨基糖构建块。这些产品将被精制成糖基供体或低聚糖合成的受体。重复应用金属催化的氨基糖基化方法将完成合成别三聚氰胺二糖的简明路线。这种灵活的合成方案将使异丙三胺头基类似物能够在后期附着到二糖上，为研究几丁质酶的结构、机理和抑制作用提供化学探针。研究工作的一个关键要素将是巴纳德学院本科生继续参与该项目的所有方面，使学生能够贡献该领域的基础知识，同时鼓励他们从事化学和与健康相关的职业。

DESCRIPTION (provided by applicant): Metal-catalyzed intramolecular nitrogen atom delivery will be developed as a method for the synthesis of a wide range of 2-amino sugar frameworks, including the disaccharide portion of the chitinase inhibitor allosamidin. Conditions will be optimized for conversion of glycal carbamates to the corresponding metalla acyl nitrenes, initiating nitrogen insertion into the electron-rich glycal alkene, followed by in situ glycosylation with a minimum of glycosyl acceptor. The overall amidoglycosylation process will provide 2-amino sugar building blocks with high stereoselectivity in the new C-2-N connection as well as at the anomeric center. The products will be elaborated to function as either glycosyl donors or acceptors for di- and oligosaccharide synthesis. Iterative application of the metal-catalyzed amidoglycosylation methodology will allow completion of a concise synthetic route to the allosamidin disaccharide. The flexible synthesis plan will enable late-stage attachment of allosamidin head group analogues to the disaccharide, offering chemical probes for the study of chitinase structure, mechanism, and inhibition. A crucial element of the research effort will be the continuing involvement of Barnard College undergraduates in all aspects of the project, enabling students to contribute fundamental knowledge in the field while encouraging them to pursue careers in chemistry and the health-related professions.