Amidoglycosylation Reactions of Glycal Metallanitrenes

描述（由申请人提供）：金属催化的分子内氮原子递送将被开发为一种合成多种2-氨基糖框架的方法，包括几丁质酶抑制剂allosamidin的双糖部分。优化氨基甲酸乙二醇酯转化为相应的金属酰基亚硝基的条件，首先将氮插入富电子的乙二醇烯烃中，然后用最少的糖基受体进行原位糖基化。整个氨基糖基化过程将提供在新的C-2-N连接以及在端粒中心具有高立体选择性的2-氨基糖构建块。产物将被阐述为二糖和低聚糖合成的糖基供体或受体。金属催化氨基糖基化方法的迭代应用将允许完成一个简洁的合成路线到异胺嘧啶二糖。灵活的合成计划将使异氨嘧啶头基类似物后期附着在双糖上，为研究几丁质酶的结构、机制和抑制作用提供化学探针。研究工作的一个关键因素将是巴纳德学院的本科生继续参与项目的各个方面，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.