Stereoselective glycosylation via H-bond-mediated aglycone delivery

通过氢键介导的糖苷配基递送进行立体选择性糖基化

• 批准号: 1800350
• 负责人: Alexei Demchenko
• 金额: $ 45万
• 依托单位: University of Missouri-Saint Louis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800350&HistoricalAwards=false
• 关键词: Stereoselective; glycosylation; via; bond; mediated

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.

化学系化学合成项目支持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。 Demchenko 教授的研究小组正在开发新方法来完成将两个糖分子连接在一起的反应。这些称为糖基化的反应本质上是用于组装广泛的生物过程中普遍存在的碳水化合物结构类型，并且正在开发的糖基化反应的应用范围从治疗策略到诊断策略。这项工作的关键是更好地理解并进一步开发 Demchenko 小组在上一个资助期间发现的独特反应途径。 这一发现使得能够以高度选择性的方式构建连接两种糖的键。该项目位于有机化学、碳水化合物化学和机械化学的交叉点，非常适合各级科学家的教育。本研究正在研究 PI 小组发现的氢键介导的糖苷配基传递 (HAD) 反应途径的机制和实践方面。这项工作的目标是完全控制糖基化的立体选择性。考虑到这一点，正在研究两种现象。第一种方法是两种先前开发的方法，溴促进的糖基化和 HAD 反应以一种为 α-和 β-糖基化提供更高立体选择性的方式组合。第二，构象开关正在被开发作为增强 HAD 反应实用性的手柄。这些努力通过提供新的合成能力来战略性地推进糖科学领域的发展，以获得具有更好立体控制和更高产量的具有挑战性的聚糖和糖复合物。所开发的方法有助于改善哺乳动物糖组和微生物聚糖关键靶标的合成，具有作为治疗剂或诊断平台的潜在应用。拟议研究的成功完成不仅推动了糖基化领域的发展，而且还为更广泛的化学、生物和医学科学做出了贡献。该计划成功的一个重要因素是本科生和研究生的积极参与，他们在研究方法方面接受了扎实的培训，并致力于解决重要的综合挑战。学生在 PI 实验室中获得的积极培训以及强大的出版和演示记录正在为他们在学术界和工业界的领导地位做好准备。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Carbohydrate Experiments in the Organic Laboratory: A Robust Synthesis and Modification of Thioglycosides

• DOI: 10.1021/acs.jchemed.9b00446
• 发表时间: 2019-10-01
• 期刊: JOURNAL OF CHEMICAL EDUCATION
• 影响因子: 3
• 作者: Mannino, Michael P.;Dunteman, Ariel P.;Demchenko, Alexei, V
• 通讯作者: Demchenko, Alexei, V

Palladium(II)-assisted activation of thioglycosides.

• DOI: 10.1039/d1ob00004g
• 发表时间: 2021-03-11
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Escopy S;Singh Y;Demchenko AV
• 通讯作者: Demchenko AV

Defining the Scope of the Acid-Catalyzed Glycosidation of Glycosyl Bromides.

• DOI: 10.1002/chem.201904185
• 发表时间: 2020-01-22
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Singh Y;Demchenko AV
• 通讯作者: Demchenko AV

Bismuth(iii) triflate as a novel and efficient activator for glycosyl halides.

• DOI: 10.1039/d1ob00093d
• 发表时间: 2021-04-14
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: Steber HB;Singh Y;Demchenko AV
• 通讯作者: Demchenko AV

A Highly Efficient Glycosidation of Glycosyl Chlorides by Using Cooperative Silver(I) Oxide-Triflic Acid Catalysis.

• DOI: 10.1002/chem.201905576
• 发表时间: 2020-06-26
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Geringer SA;Singh Y;Hoard DJ;Demchenko AV
• 通讯作者: Demchenko AV