Reagent Controlled Selective Dehydrative Glycosylation Reactions

在这个由化学部门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、有效的化学方法，将单糖分子结合成被称为低聚糖的糖链。低聚糖存在于细胞表面，在介导免疫系统反应中起着重要作用。目前正在开发用于构建定义明确的低聚糖的试剂，其速度比目前可能的要快得多，并且产生的废物也更少。这项研究计划影响了利用低聚糖的科学和技术，包括农业、生物技术和制药科学。班尼特教授的小组一直致力于培养本科生和研究生的化学研究方法。他们还通过向马萨诸塞州萨默维尔市的高中生介绍有机化学以及如何使用有机化学来创建生物相关分子，参与了向他们的推广工作。萨默维尔的社区是多元化的，所以这个项目覆盖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，这包括用磺酰氯激活半缩醛，而α连接的脱氧糖可以用环丙烯阳离子促进糖基化从半缩醛合成。目前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相容性来检查这种化学的普遍性。2)研究该化学在天然产物线性和收敛合成五糖和六糖中的应用。3)研究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，目前无法通过单一化学转化直接合成。总之，这些研究可能导致难以接近的糖苷键的可靠立体选择性构建方法。从这些研究中获得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低聚糖和糖缀合物库。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.