Glycosyl Sulfonates for the Construction of Difficult Glycosidic Linkages

通过这一奖项，美国国家科学基金会化学部的化学合成计划支持塔夫茨大学的Clay Bennett教授的研究，他正在开发一种方法，使糖分子在特定位置相互附着，而不形成产品混合物。能够控制糖分子的附着是很重要的，因为它影响这些化合物在不同系统中的反应活性。糖分子链被称为低聚糖，存在于细胞表面，是植物的结构成分，通常控制着生物过程。班尼特教授和他的研究小组将确定糖分子的哪些成分与一种试剂最匹配，以帮助形成所需的连接。然后，他们将通过制造一种已知的抗生素化合物来测试他们从这些研究中学到的东西。确定如何使糖分子在特定位置连接在一起，将提高低聚糖合成的效率，并减少与分离产品混合物相关的浪费。这项研究的结果影响到所有需要碳水化合物合成的活动领域，包括农业、化工和制药行业。该项目还包括向高中化学学生推广介绍糖分子化学的活动。班尼特实验室正在使用磺酰氯促进剂来控制脱氧糖糖基化反应的立体化学结果。由于缺乏导向基团，这些反应很难控制，因此找到实现这种选择性的方法很重要。正在进行三个具体的研究领域：1)监测不同脱氧糖和磺酰氯的反应活性，以创建一个数据库，编目哪种糖最适合哪种糖，2)确定控制这些转化的化学相互作用，以及3)展示该方法在合成糖霉素B方面的实用性。从这些研究中吸取的经验教训可能允许合成具有挑战性的寡糖，而不需要浪费的分离程序。该计划将为不同的研究生、本科生和高中生提供一个极好的培训环境。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemical Synthesis Program of the NSF Chemistry Division is supporting the research of Professor Clay Bennett of Tufts University who is developing ways to make sugar molecules attach to each other at specific locations without forming mixtures of products. Being able to control the attachment of sugar molecules is important because it influences the reactivity of these compounds in different systems. Chains of sugar molecules are called oligosaccharides and are found on the surfaces of cells, are structural components of plants, and often control biological processes. Professor Bennett and his research group will determine which components of sugar molecules match best with a reagent to help form the desired connections. They will then test what they learn from these studies by making a known antibiotic compound. Determining how to make sugar molecules link together at specific locations will increase efficiency in oligosaccharide synthesis and decrease waste associated with separating mixtures of products. The results of this research impact all areas of activity that require carbohydrate synthesis, including agricultural, chemical, and pharmaceutical industries. This project also involves outreach activities to high school chemistry students to introduce the chemistry of sugar molecules.The Bennett lab is using sulfonyl chloride promoters to control the stereochemical outcome of glycosylation reactions of deoxysugars. These reactions are difficult to control due to the lack of a directing group so finding ways to achieve this selectivity is important. Three specific areas of investigation are being pursued: 1) monitoring the reactivity of different deoxy sugars and sulfonyl chlorides to create a database cataloging which promoter is best for which sugar, 2) determining the chemical interactions that control these transformations, and 3) demonstrating the utility of the method with the synthesis of saccharomicin B. Lessons learned from these studies may allow for the synthesis of challenging oligosaccharides without the need for wasteful separation procedures. This program will provide an excellent training environment for a diverse group of graduate, undergraduate, and high school students.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.