Synthetic tools for glycobiology research

糖生物学研究的合成工具

• 批准号: 1301330
• 负责人: David Mootoo
• 金额: $ 36万
• 依托单位: CUNY Hunter College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1301330&HistoricalAwards=false
• 关键词: Synthetic; tools; glycobiology; research

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Professor David R. Mootoo, of the Department of Chemistry at Hunter College of The City University of New York, will develop a broad-based synthesis of glycomimetics. The methodology centers on the reaction of sugar-substituted crotyl-stannanes and boronates with chiral aldehydes. A key aspect of this study will be the examination of how substrate effects, the choice of Lewis acid catalyst, and the reaction conditions can be tuned to control stereoselectivity. A major focus will be on the synthesis of two classes of glycomimetics that have attracted much attention in glycobiology research, C- and carba-,glycoside analogues of O-glycosides in which the glycoside or ring oxygen, respectively, is replaced with a carbon substituent. The proposed crotylation method promises robust syntheses of these materials and may also be appropriate for unusual O-glycosides for which conventional O-glycoside synthesis is problematic. Specific synthetic goals are analogues of inositol hexosamines that activate protein phosphatases (PPs) and the immunostimulatory glycolipid alpha-galactosylceramide, and which provide a platform for the development of the scope of the crotylation methodology. Additional studies will include investigation of the conformational and PP activating behavior of the hexosamine inositol mimetics and determination of the cytokine profiles elicited by the glycolipid analogues. Successful development of the proposed research will advance the use of carbohydrate reagents and auxiliaries in asymmetric synthesis, particularly in regard to applications in glycobiology, and provide insight on how carbohydrate ligands interact with and control the function of proteins, an important component of bioregulatory behavior. The interdisciplinary underpinnings of this research provide a framework for innovative strategies in the training of science students, from pre-undergraduate to graduate, including groups that are historically underrepresented in the sciences.

在这个项目中，由化学部化学综合计划资助，纽约市亨特学院化学系的戴维·R·穆特（David R. 该方法集中于糖取代的crotyl-stannanes和手性醛的反应。这项研究的一个关键方面是检查底物效应，刘易斯酸催化剂的选择以及可以调节反应条件以控制立体选择性的方式。主要重点将是合成两类糖基化学的糖基因研究，这些糖基因糖苷的糖苷和糖苷类似物分别以糖苷或环氧的形式，用碳取代代替糖苷或环氧。所提出的附带方法有望对这些材料的鲁棒合成，也可能适用于常规O-糖苷合成的异常O-糖苷，这是有问题的。特定的合成目标是肌醇六糖的类似物，这些乙酰六胺激活蛋白质磷酸酶（PPS）和免疫刺激性糖脂α-半乳糖基酰胺，并为开发链依基方法范围提供了一个平台。 其他研究将包括研究己糖胺肌醇模拟物的构象和PP激活行为，并测定糖脂类似物引起的细胞因子谱。 拟议研究的成功开发将推动碳水化合物试剂和辅助剂在不对称合成中的使用，尤其是在糖生物学中的应用方面，并提供有关碳水化合物配体如何与碳水化合物相互作用并控制蛋白质功能的洞察力，这是蛋白质的功能，蛋白质的功能，是生物测量行为的重要成分。这项研究的跨学科基础为科学学生培训的创新策略提供了一个框架，从不前专业到研究生，包括科学中人数不足的群体。