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

在化学系化学合成计划的支持下，塔夫茨大学的克莱·S·班尼特教授正在开发控制脱氧糖合成的方法。脱氧糖是许多生物活性天然产物的重要组成部分，但只有通过化学合成才能获得。班尼特教授正在开发新的化学方法来合成脱氧糖，并控制其三维结构。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，包括自然产生的脱氧糖。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极好的合成和碳水化合物化学方面的培训，并将通过推广和让高中生访问Tuft进行实验来向高中化学学生介绍有机化学。在这个奖项下，Bennett小组将扩展一种合成脱氧糖的方法，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苷(TBS糖苷)。糖基磺酸盐直接与氧亲核试剂反应生成具有高立体选择性的新的糖苷键。类似地，TBS糖苷可以被Lewis酸活化，与亲核试剂反应，得到同样具有高选择性的产品。重要的是，这两种方法是相辅相成的：糖基磺酸盐方法被用来生成特定糖苷键的一种非对映异构体，而TBS糖苷化学被用来创建另一种。Bennett研究团队将把这些反应应用于一些低聚糖的合成，以研究该方法的一般性，他们计划使用初级动力学同位素实验来探索反应的机理，着眼于建立这些反应歧管的SN1和SN2性质。这一奖项反映了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 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.