Toward a Better Understanding of Factors Controlling Selectivity in Deoxy Sugar Oligosaccharide Synthesis

在化学系化学合成项目的支持下，塔夫茨大学的Clay S. Bennett教授正在开发控制脱氧糖合成的方法。脱氧糖是许多具有生物活性的天然产物的重要组成部分，但只能通过化学合成获得。班尼特教授正在开发一种新的化学方法来合成脱氧糖并控制它们的三维结构。他的实验室正在研究正在开发的转化机制，以便这些反应可以更广泛地应用于合成其他类别的化合物，包括天然存在的脱氧糖。这项研究有可能影响许多学术和工业实验室，包括农业、化学和制药行业的实验室。该项目将为本科生和研究生提供合成和碳水化合物化学方面的优秀培训，并将通过外展和让高中生参观塔夫茨大学并进行实验，向高中化学学生介绍有机化学。根据该奖项，Bennett小组将扩展脱氧糖的合成方法，该方法包括激活糖半缩醛作为糖基磺酸盐或叔丁基二甲基硅基糖苷（TBS糖苷）。糖基磺酸盐与氧亲核试剂直接反应生成具有高立体选择性的新糖苷键。同样，TBS糖苷可以被路易斯酸激活，与亲核试剂反应，产生同样具有高选择性的产物。重要的是，这两种方法是相互补充的：糖基磺酸盐方法用于创建特定糖苷键的一种非对映体，而TBS糖苷化学方法用于创建另一种非对映体。Bennett研究小组将把这些反应应用于合成一些低聚糖，以研究该方法的普遍性，并计划利用初级动力学同位素实验来探索反应的机理，以建立这些反应流形的SN1和SN2性质。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。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Clay S. Bennett of Tufts University is developing methods for controlling the synthesis of deoxy sugars. Deoxy sugars are an important component of many biologically active natural products but are only available through their chemical synthesis. Professor Bennett is developing new chemistry to synthesize deoxy sugars with control over their three-dimensional structure. His lab is studying the mechanisms of the transformations being developed, so that the reactions can be more generally applied to the synthesis of other classes of compounds including naturally occurring deoxy sugars. This research has the potential to impact a number of academic and industrial laboratories including those in the agricultural, chemical, and pharmaceutical industries. The project will provide excellent training in synthetic and carbohydrate chemistry for undergraduate and graduate students, and will also be used to introduce high school chemistry students to organic chemistry through outreach and by having high school students visit and run experiments at Tufts.Under this award, the Bennett group will expand upon an approach to the synthesis of deoxysugars that involves activating sugar hemiacetals as either glycosyl sulfonates or tert-butyldimethylsilyl glycosides (TBS glycosides). The glycosyl sulfonates react directly with oxygen nucleophiles to generate new glycosidic linkages with high levels of stereoselectivity. Similarly, the TBS glycosides can be activated with Lewis Acids to react with nucleophiles to afford products also with high levels of selectivity. Importantly, these two methods are complementary to one another: the glycosyl sulfonate approach is being used to create one diastereomer of a particular glycosidic linkage, while the TBS glycoside chemistry is being used to create the other. The Bennett research team will apply these reactions to the synthesis of a number of oligosaccharides to investigate the generality of the method, and they plan to explore the mechanism of the reactions using primary kinetic isotope experiments with eye toward establishing the SN1 vs. SN2 nature of these reaction manifolds.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.