Umpolung Reactivity in Stereoselective Synthesis of 2-Deoxy Glycosides and Thioglycosides

2-脱氧糖苷和硫代糖苷立体选择性合成中的 Umpolung 反应性

• 批准号: 1213352
• 负责人: Jianglong Zhu
• 金额: $ 36万
• 依托单位: University of Toledo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1213352&HistoricalAwards=false
• 关键词: Umpolung; Reactivity; Stereoselective; Synthesis; Deoxy

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Jianglong Zhu of the Department of Chemistry at University of Toledo will develop umpolung reactivity-based glycosylations for stereoselective syntheses of biologically important 2-deoxy glycosides and thioglycosides. Despite recent accomplishments in the development of glycosylation methodology, stereoselective synthesis of 2-deoxy sugars remains challenging because of the lack of a directing group at the C-2 position. This project focuses on investigating reactions of stereochemically defined 2-deoxy glycosyl anions with sugar-derived peroxo and disulfide acceptors for stereoselective preparation of 2-deoxy glycosides and thioglycosides. In addition, experimental efforts will be taken to understand the mechanism of these umpolung reactivity-based glycosylations. Successful accomplishment of this project will have a significant impact on synthetic organic community, because it will provide a strategy that complements current methods in the stereoselective synthesis of structurally challenging and biologically valuable 2-deoxy glycosides and thioglycosides. This project could lead to the synthesis of a variety of sugar based therapeutic agents. In addition, it will provide excellent training for undergraduate and graduate students, K-12 science teachers, and high school students, including those from groups currently underrepresented in the chemical sciences.

在该项目中，托莱多大学化学系的朱江龙教授将开发基于umpolung反应性的糖基化反应，用于生物重要的2-脱氧糖苷和硫代糖苷的立体选择性合成。 尽管最近在糖基化方法的发展方面取得了成就，但由于在C-2位缺乏导向基团，2-脱氧糖的立体选择性合成仍然具有挑战性。 本项目的重点是研究立体化学定义的2-脱氧糖基阴离子与糖衍生的过氧和二硫键受体的反应，用于立体选择性制备2-脱氧糖苷和硫代糖苷。 此外，将采取实验努力，以了解这些umpolung反应性为基础的糖基化的机制。该项目的成功完成将对合成有机社区产生重大影响，因为它将提供一种战略，补充目前的方法，立体选择性合成的结构具有挑战性和生物价值的2-脱氧糖苷和硫代糖苷。 该项目可能导致各种糖基治疗剂的合成。 此外，它将为本科生和研究生，K-12科学教师和高中生提供出色的培训，包括那些目前在化学科学领域代表性不足的群体。