Amidoglycosylation Reactions of Glycal Metallanitrenes

糖金属氮烯的酰胺糖基化反应

• 批准号: 6919537
• 负责人: CHRISTIAN M. ROJAS
• 金额: $ 0.93万
• 依托单位: BARNARD COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6919537
• 关键词: X ray crystallography; alkenes; aminosugar; carbamates; carbohydrate biosynthesis; catalyst; chemical synthesis; chitin; disaccharides; enzyme inhibitors; free radicals; glycosylation; metals; method development; nitrene; nuclear magnetic resonance spectroscopy; stereochemistry

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.

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用于合成宽范围的2-氨基糖框架的方法，包括几丁质酶抑制剂阿洛酰胺的二糖部分。将优化条件以将糖基氨基甲酸酯转化为相应的金属酰基氮烯，引发氮插入富电子的糖基烯烃中，然后用最少的糖基受体进行原位糖基化。整个酰胺基糖基化过程将在新的C-2-N连接以及异头中心提供具有高立体选择性的2-氨基糖结构单元。产物将被精心制作，以作为二-和寡糖合成的糖基供体或受体。重复应用金属催化的酰胺基糖基化方法将允许完成一个简洁的合成路线的allosamidin二糖。灵活的合成方案将使后期连接allosamidin头基类似物的二糖，几丁质酶的结构，机制和抑制的研究提供化学探针。研究工作的一个关键因素将是巴纳德学院本科生继续参与该项目的各个方面，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健康相关专业的职业。