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.

本研究由化学系化学合成项目资助，大卫R.纽约亨特学院化学系的Mootoo将开发一种基础广泛的糖模拟物合成方法。 该方法集中在糖取代的巴豆基锡烷和硼酸酯与手性醛的反应。本研究的一个关键方面将是如何检查底物的影响，选择的刘易斯酸催化剂，和反应条件可以调整，以控制立体选择性。一个主要的重点将是在糖生物学研究，C-和碳-，O-糖苷的糖苷类似物，其中的糖苷或环氧，分别被取代的碳取代基的糖模拟物的两个类别的合成。建议的巴豆酰化方法承诺稳健的合成这些材料，也可能是适当的不寻常的O-糖苷，传统的O-糖苷合成是有问题的。具体的合成目标是激活蛋白磷酸酶（PP）和免疫刺激性糖脂α-半乳糖神经酰胺的肌醇己糖胺类似物，并为巴豆酰化方法的范围的发展提供了一个平台。 其他研究将包括调查的构象和PP激活行为的己糖胺肌醇模拟物和确定的细胞因子的档案引起的糖脂类似物。 拟议研究的成功开发将促进碳水化合物试剂和助剂在不对称合成中的使用，特别是在糖生物学中的应用，并提供有关碳水化合物配体如何与蛋白质相互作用和控制蛋白质功能的见解，蛋白质是生物调节行为的重要组成部分。这项研究的跨学科基础提供了一个框架，创新战略的科学学生的培训，从大学预科到研究生，包括历史上在科学中代表性不足的群体。