Stable and Easily Activated Thioglycosides for the Stereoselective Synthesis of Oligosaccharides

化学系的化学合成计划支持贾斯汀·雷根斯教授的项目。 Ragains教授是路易斯安那州立大学化学系的教员。 他正在研究使单糖相互结合的合成方法。 这些方法对于寡糖的合成至关重要。 寡聚核苷酸在生物学中发挥着重要作用，但大多数都知之甚少。 由于分离和纯化的困难，为生物学研究获得可用数量的寡糖需要化学合成。 寡糖的合成存在许多技术缺陷，包括化学中间体稳定性差和技术上具有挑战性的程序;这些限制正在由本项目解决。 这项工作的科学进展导致寡糖合成的改进，这反过来又促进了生物学的发现，并使寡糖疫苗和治疗剂的开发成为可能。 Ragains教授致力于在各级教育中为妇女和科学领域代表性不足的少数民族以及贫困学生提供科学培训。 公共宣传活动包括为来自贫困背景的巴吞鲁日高中学生举办夏季化学实验室活动。 该项目涉及开发4-芳基-3-丁烯基硫代糖苷（ABTG）作为一类O-糖基化亲电试剂，其将硫代糖苷的稳定性与使用催化酸直接活化糖基三氯乙酰亚胺酯联合收割机结合。 使用源自哺乳动物寡糖中常见糖的ABTG的O-糖基化方法正在研究中。 此外，正在开发利用其不寻常的激活机制的ABTG的1，2-顺式选择性糖基化。 最后，使用ABTG作为关键中间体合成人乳低聚糖乳糖-N-新四糖正在进行中。 该研究计划提供了一系列ABTG中的O-糖基化亲电试剂，可供几乎没有化学合成培训的科学家使用。 Boc-和Fmoc-保护的氨基酸的公认效用已经将多肽合成置于非专家的范围内。同样，ABTG一旦完全发展起来，就将寡糖的合成交给了需要这些化合物用于糖生物学研究的科学家。 该教育计划涉及向处境不利的高中生开展外联活动，其中许多是妇女和代表性不足的少数群体。 外联活动包括夏季化学实验室活动，面向实验室技能的发展，帮助这些学生在大学水平的实验室课程。 碳水化合物化学是这些外联活动的一个特别重点。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Justin Ragains. Professor Ragains is a faculty member in the Department of Chemistry at Louisiana State University. He is developing synthetic methods for bonding monosaccharides to each other. These methods are critical for the synthesis of oligosaccharides. Oligosaccharides, in turn, play important roles in biology, most of which are poorly understood. Because of difficulties in isolation and purification, obtaining serviceable quantities of oligosaccharides for biological studies requires chemical synthesis. The synthesis of oligosaccharides suffers from a number of technological shortcomings including poor stability of chemical intermediates and technically challenging procedures; these limitations are being addressed by the current project. Scientific advances from this work result in improved syntheses of oligosaccharides, which in turn facilitate discoveries in biology and enable the development of oligosaccharide vaccines and therapeutics. Professor Ragains is committed to the scientific training of women and underrepresented minorities in the sciences and underprivileged students at all levels of education. Public outreach activities include summer chemistry lab activities for Baton Rouge high school students from underprivileged backgrounds. This project involves the development of 4-aryl-3-butenylthioglycosides (ABTGs) as a class of O-glycosylation electrophiles that combine the stability of thioglycosides with the straightforward activation of glycosyl trichloroacetimidates using catalytic acids. O-Glycosylation methods using ABTGs derived from sugars that are commonly found in mammalian oligosaccharides are under investigation. In addition, 1,2-cis-selective glycosylations with ABTGs that exploit their unusual mechanism of activation are being developed. Finally, a synthesis of the human milk oligosaccharide lacto-N-neotetraose using ABTGs as key intermediates is underway. This research program provides a series of O-glycosylation electrophiles in ABTGs that can be utilized by scientists with little training in chemical synthesis. The well-established utility of Boc- and Fmoc-protected amino acids has placed polypeptide synthesis within the reach of non-experts. Similarly, the ABTGs saccharides, when fully developed, place the synthesis of oligosaccharides in the hands of scientists who require these compounds for the study of glycobiology. The educational plan involves outreach to underprivileged high school students, many of whom are women and underrepresented minorities. Outreach activities include summer chemistry lab activities geared toward the development of laboratory skills that assist these students in college-level laboratory courses. Carbohydrate chemistry is a particular focus of these outreach activities.