Synthetic tools for glycobiology research

在这个由化学系化学合成项目资助的项目中，纽约城市大学亨特学院化学系的David R. Mootoo教授将开发一种基础广泛的糖仿生学合成方法。该方法以糖取代丁基锡烷和硼酸盐与手性醛的反应为中心。本研究的一个关键方面将是检查底物效应、刘易斯酸催化剂的选择和反应条件如何调整以控制立体选择性。主要的焦点将集中在糖生物学研究中备受关注的两类糖拟物的合成，C-和碳-，o -糖苷的糖苷类似物，其中糖苷或环氧分别被碳取代基取代。所提出的丁基化方法保证了这些材料的稳定合成，也可能适用于非常规的o -糖苷，而传统的o -糖苷合成是有问题的。特定的合成目标是肌醇己糖胺的类似物，可以激活蛋白磷酸酶（PPs）和免疫刺激糖脂α -半乳糖神经酰胺，并为克丁基化方法的范围的发展提供了一个平台。其他研究将包括己糖胺肌醇模拟物的构象和PP激活行为的调查，以及糖脂类似物引发的细胞因子谱的测定。该研究的成功发展将促进碳水化合物试剂和助剂在不对称合成中的应用，特别是在糖生物学方面的应用，并为碳水化合物配体如何与生物调节行为的重要组成部分蛋白质相互作用和控制功能提供见解。本研究的跨学科基础为培养从本科预科到研究生的理科生提供了一个创新策略框架，包括历史上在科学领域代表性不足的群体。

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.