Reagent Controlled Selective Dehydrative Glycosylation Reactions

在这项由化学系化学合成计划资助的项目中，塔夫茨大学化学系的克莱·S·班尼特教授正在开发新的、高效的化学方法，将单糖分子结合成称为低聚糖的糖链。低聚糖存在于细胞表面，在调节免疫系统反应中起着重要作用。正在开发试剂盒，以便以比目前可能的速度更快、产生更少废物的方式构建定义明确的低聚糖。这项研究计划影响利用低聚糖的科学和技术，包括农业、生物技术和制药科学。班尼特教授的团队一直致力于对本科生和研究生进行化学研究方法的培训。他们还通过向马萨诸塞州萨默维尔的高中生提供有机化学的介绍，以及如何利用有机化学来创造与生物相关的分子，参与了对他们的外联活动。萨默维尔的社区是多样化的，所以这个项目接触到了许多来自STEM领域历史上代表性不足的群体的学生。班尼特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，这涉及到用磺酰氯激活半缩醛，而用环丙烯阳离子促进的糖基化可以从半缩醛合成α-连接的脱氧糖。正在进行三个方面的研究：1)通过探索其与一系列脱氧糖偶联伙伴的兼容性来检查这种化学的一般性。2)该化学在天然产物线性聚合合成五糖和六糖中的应用研究。3)研究以确定这种化学是否可以用于构建β-鼠李糖苷，这是一类重要的碳水化合物连接，目前不能在单一的化学转化中直接合成。总之，这些研究可能会导致可靠的立体选择性构建难以进入的糖苷键的方法。从这些研究中吸取的经验教训也可能允许将这种化学应用于其他类型的糖苷，甚至寡糖和糖共轭物库。这样的文库将为药物发现开辟新的途径，并加快糖生物学领域的研究步伐。

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.