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）：金属催化的分子氮原子递送将作为合成各种2-氨基糖框架的方法，包括几丁质酶抑制剂同酰胺素的二糖部分。将优化条件，以将糖氨基甲酸酯转化为相应的金属酰基硝酸，从而启动氮插入到富含电子的甘氨酸烯烃中，然后以最少的糖基受体的原位糖基化。总体酰胺基化过程将在新的C-2-N连接以及异体中心提供高立体选择性的2-氨基糖构建块。这些产品将被详细阐述作为糖基供体或寡糖合成的受体。金属催化的胺糖基化方法的迭代应用将允许完成通往异胺二糖的简明合成途径。柔性合成计划将使同胺类头组类似物对二糖的后期附着，提供用于研究几丁质酶结构，机制和抑制作用的化学探针。研究工作的关键要素将是巴纳德学院大学生在项目的各个方面的持续参与，使学生能够在该领域贡献基本知识，同时鼓励他们从事化学和与健康有关的职业。