Reagent Controlled Selective Dehydrative Glycosylation Reactions

试剂控制的选择性脱水糖基化反应

• 批准号: 1566233
• 负责人: Clay Bennett
• 金额: $ 43.33万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1566233&HistoricalAwards=false
• 关键词: Reagent; Controlled; Selective; Dehydrative; Glycosylation

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Professor Clay S. Bennett of the Department of Chemistry at Tufts University is developing new, efficient chemical approaches to combine single sugar molecules into chains of sugars called oligosaccharides. Oligosaccharides are found on the surfaces of cells and are important in mediating immune system responses. Reagent kits are being developed for the general construction of well-defined oligosaccharides much faster than is currently possible and with the production of less waste. This research program impacts science and technologies that utlize oligosaccharides, including agriculture, biotechnology and pharmaceutical science. Professor Bennett's group has an ongoing commitment to training undergraduate and graduate students in chemistry research methods. They are also involved in outreach to Somerville, MA high school students by providing them with an introduction to organic chemistry and how it can be used to create biologically relevant molecules. The community of Somerville is diverse, so this program reaches many students from groups that are historically underrepresented in STEM fields.Prof. Bennett is studying how to place the stereochemical outcome of a glycosylation reaction entirely under control of the promoter. For beta-selective glycosylations this involves activating hemiacetals with sulfonyl chlorides, while alpha-linked deoxy-sugars can be synthesized from hemiacetals using cyclopropenium cation promoted glycosylations. Three areas of investigation are being pursued: 1) an examination of the generality of this chemistry by exploring its compatibility with an array of deoxy-sugar coupling partners. 2) A study of the utility of this chemistry in the linear and convergent synthesis of penta- and hexasaccharides from natural products. 3) Studies to determine if this chemistry can be applied to the construction of beta-rhamnosides, an important class of carbohydrate linkages that currently cannot be synthesized directly in a single chemical transformation. Together, these studies may result in methods for the reliable stereoselective construction of difficult to access glycosidic linkages. Lessons learned from these studies also may permit the application of this chemistry to other classes of glycosides or even oligosaccharide and glycoconjugate libraries. Such libraries would open up new avenues for drug discovery and accelerate the pace of research in the field of glycobiology.

在这个由化学系化学合成项目资助的项目中，塔夫茨大学化学系的 Clay S. Bennett 教授正在开发新的、高效的化学方法，将单个糖分子结合成称为寡糖的糖链。 低聚糖存在于细胞表面，对于介导免疫系统反应很重要。 正在开发用于构建明确寡糖的试剂盒，其速度比目前快得多，并且产生的废物更少。该研究计划影响利用寡糖的科学和技术，包括农业、生物技术和制药科学。贝内特教授的团队一直致力于培养本科生和研究生的化学研究方法。 他们还参与了对马萨诸塞州萨默维尔高中生的宣传活动，向他们介绍有机化学以及如何使用它来创建生物学相关的分子。 萨默维尔的社区是多元化的，因此该计划吸引了许多来自历史上在 STEM 领域代表性不足的群体的学生。 Bennett 正在研究如何将糖基化反应的立体化学结果完全置于启动子的控制之下。 对于β-选择性糖基化，这涉及用磺酰氯激活半缩醛，而α-连接的脱氧糖可以使用环丙烯鎓阳离子促进的糖基化从半缩醛合成。 正在进行三个研究领域：1）通过探索其与一系列脱氧糖偶联伙伴的兼容性来检查该化学的普遍性。 2) 研究该化学在天然产物五糖和六糖的线性聚合合成中的应用。 3）研究以确定这种化学是否可以应用于β-鼠李糖苷的构建，β-鼠李糖苷是一类重要的碳水化合物键，目前无法在单一化学转化中直接合成。 总之，这些研究可能会产生可靠的立体选择性构建难以接近的糖苷键的方法。从这些研究中汲取的经验教训也可能允许将这种化学应用于其他类别的糖苷，甚至寡糖和糖复合物库。这些图书馆将为药物发现开辟新途径，并加快糖生物学领域的研究步伐。