Stereoselective glycosylation via H-bond-mediated aglycone delivery

化学系的化学合成项目支持Alexei Demchenko教授的项目。Demchenko教授是密苏里大学圣路易斯分校化学与生物化学系的教员。德姆琴科教授的研究小组正在开发新的方法来完成将两个糖分子连接在一起的反应。这些反应被称为糖基化，本质上是为了组装在广泛的生物过程中普遍存在的碳水化合物结构类型，糖基化反应的应用范围从治疗到诊断策略。这项工作的关键是更好地理解和进一步开发Demchenko小组在上一个资助期间发现的独特反应途径。这一发现使得以高度选择性的方式在连接两个糖的键上构建成为可能。本课题处于有机化学、碳水化合物化学和机械化学的交叉点，适合各级科学家的教育。这项研究正在研究由PI小组发现的氢键介导的苷元传递（HAD）反应途径的机制和实践方面。本工作的目的是完全控制糖基化的立体选择性。考虑到这一点，目前正在研究两种现象。首先，两种先前开发的方法，溴促进的糖基化和HAD反应以一种对-和-糖基化提供更高立体选择性的方式结合在一起。在第二方面，构象开关正在开发作为手柄，以提高HAD反应的效用。这些努力通过提供新的合成能力来获得具有更好立体控制和更高收率的具有挑战性的聚糖和糖缀合物，从而战略性地推进了糖科学领域。所开发的方法有助于改进从哺乳动物聚糖和微生物聚糖中合成关键靶点的方法，具有作为治疗剂或诊断平台的潜在应用前景。这项研究的成功完成不仅推动了糖基化领域的发展，而且对化学、生物和医学科学做出了更大的贡献。这个项目的成功离不开本科生和研究生的积极参与，他们接受了扎实的研究方法训练，并致力于解决重要的综合挑战。学生们在PI的实验室中获得的有力训练和良好的发表和演讲记录，为他们在学术界和工业界的领导地位做好了准备。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Alexei Demchenko. Professor Demchenko is a faculty member in the Department of Chemistry and Biochemistry at the University of Missouri - St. Louis. Professor Demchenko's research group is developing new methods for accomplishing reactions that hook two sugar molecules together. These reactions, called glycosylations, are essentially for assembling the types of carbohydrate structures that are prevalent in a wide range of biological processes and applications of the glycolsylation reactions being developed range from therapeutic to diagnostic strategies. Key to the effort is work both better understand and further develop a unique reaction pathway that was discovered by the Demchenko group during the previous funding period. This discovery is enabling the construction on the bond connecting the two sugars in a highly selective manner. The project lies at the interface of organic, carbohydrate, and mechanistic chemistry, and it is well suited for the education of scientists at all levels. This study is investigating both mechanistic and practical aspects of the H-bond-mediated Aglycone Delivery (HAD) reaction pathway discovered by the PI's group. The goal of the work is to completely control the stereoselectivity of the glycosylation. With this in mind, two phenomena are being investigated. In the first, two previously developed methods, bromine-promoted glycosylation and HAD reaction are being combined in a manner that affords higher stereoselectivity for both alpha- and beta-glycosylation. In the second, conformational switches are being developed as handles for enhancing the utility of the HAD reaction. These endeavors are strategically advancing the field of glycosciences by offering new synthetic capabilities for obtaining challenging glycans and glycoconjugates with better stereocontrol and higher yields. The developed methods are serving to improve the synthesis of key targets from mammalian glycomes and microbial glycans with potential application as therapeutic agents or diagnostic platforms. Successful completion of the proposed research is not only advancing the field of glycosylation, but is also making contributions to the larger chemical, biological, and medical sciences. Integral to the success of this program is the active participation of undergraduate and graduate students who receive solid training in research methods and work to solve synthetic important synthetic challenges. The vigorous training and strong publication and presentation records that students are gaining in the PI's laboratory is preparing them for leading positions in academia and industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.