Stable and Easily Activated Thioglycosides for the Stereoselective Synthesis of Oligosaccharides

化学部化学合成项目支持Justin Ragains教授的项目。Ragains教授是路易斯安那州立大学化学系的教员。他正在开发单糖相互结合的合成方法。这些方法对低聚糖的合成至关重要。低聚糖，反过来，在生物学中发挥重要作用，其中大部分是知之甚少。由于分离和纯化困难，获得生物学研究所需数量的低聚糖需要化学合成。低聚糖的合成存在许多技术缺陷，包括化学中间体的稳定性差和技术上具有挑战性的程序；当前的项目正在解决这些限制。这项工作带来的科学进步改善了低聚糖的合成，这反过来又促进了生物学的发现，并使低聚糖疫苗和治疗方法得以发展。Ragains教授致力于对妇女和在科学领域代表性不足的少数群体以及各级教育中地位低下的学生进行科学培训。公共推广活动包括巴吞鲁日高中贫困家庭学生的暑期化学实验室活动。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，将硫代糖苷的稳定性与使用催化酸直接激活三氯乙酸糖基酸结合起来。使用从哺乳动物低聚糖中常见的糖衍生的abtg的o糖基化方法正在研究中。此外，1,2-顺式选择性糖基化与abtg利用其不寻常的激活机制正在开发。最后，以abtg为主要中间体合成母乳低聚糖乳酸-n -新四糖的研究正在进行中。这个研究项目提供了一系列abtg中的o -糖基化亲电试剂，这些试剂可以被很少接受化学合成训练的科学家利用。Boc-和fmoc保护氨基酸的成熟应用使多肽合成在非专家的范围内。同样，当abtg糖完全发育后，低聚糖的合成就交给了需要这些化合物来研究糖生物学的科学家。这项教育计划涉及向贫困的高中生伸出援手，其中许多是妇女和代表性不足的少数民族。拓展活动包括暑期化学实验活动，旨在培养学生的实验技能，帮助他们完成大学水平的实验课程。碳水化合物化学是这些拓展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.