Stereoselective Construction of Difficult Glycosidic Linkages

在本项目中，托莱多大学化学与生物化学系的朱江龙教授和迪尔伯恩大学自然科学系的李晓华教授正在合作开发立体选择性构建困难糖苷键的新方法。本研究通过研究结构上具有挑战性和生物学价值的糖苷键的立体选择性合成的新方法，在碳水化合物的合成中具有潜力。通过实施这一项目，PI将为高中生、K-12科学教师、本科生和研究生以及访问助理教授提供教育和培训机会。PI正在招募女性、化学科学领域代表性不足的群体以及来自经济困难家庭的人参与这项研究。此外，PI正在参与各种外展活动，以促进化学科学的教学，培训和学习。该研究的目标是构建困难的糖苷键，如β-吡喃甘露糖苷和α-硫代糖苷。具体地，β-吡喃甘露糖苷的立体选择性合成是通过动力学异头和螯合作用的双重控制下的异头O-烷基化来实现的。这种聚乙二醇型β-甘露糖基化被用于合成N-连接聚糖。S-连接的-硫代糖苷的立体选择性合成使用通过轴向糖基锂物质的亚磺酰化的非极性S-糖基化。总的来说，这些合成方法有可能为制备糖苷的现有方法增加一个重要的新维度。

AbstractIn this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Jianglong Zhu of the Department of Chemistry and Biochemistry at University of Toledo and Professor Xiaohua Li of the Department of Natural Sciences at University of Michigan-Dearborn are collaborating to develop novel approaches for stereoselective construction of difficult glycosidic linkages. This research has potential in the synthesis of carbohydrates by investigating new approaches to the stereoselective synthesis of structurally challenging and biologically valuable glycosidic linkages. By carrying out this project, the PIs will provide education and training opportunities for high school students, K-12 science teachers, undergraduate and graduate students, as well as visiting assistant professors. The PIs are recruiting women, groups underrepresented in the chemical sciences, and those from financially disadvantaged families to participate in this research. In addition, The PIs are participating in various outreach activities to promote teaching, training, and learning in chemical sciences. The research is targeting the construction of difficult glycosidic linkages such as beta-mannopyranosides and alpha-thioglycosides. Specifically, stereoselective synthesis of beta-mannopyranosides is targeted via anomeric O-alkylation under dual control of kinetic anomeric and chelation effects. This umpolung-type beta-mannosylation is being used to synthesize N-linked glycans. The stereoselective synthesis of S-linked-thioglycosides uses umpolung S-glycosylation through sulfenylation of the axial glycosyl lithium species. Collectively, these synthetic approaches have the potential to add a significant new dimension to the set of available methodologies to make glycosides.