Reagent Controlled Selective Glycosylation Reactions with Deoxy-Sugar Donors

在这个由化学部门化学合成计划资助的项目中，塔夫茨大学化学系的Clay S. Bennett教授将研究利用货架稳定糖基供体立体选择性构建脱氧糖键的方法。虽然脱氧糖结构的方法确实存在，但它们经常依赖于使用临时定向基团来控制选择性。这在它们的合成中引入了多个附加步骤。拟议的研究将包括开发一套试剂来激活脱氧糖供体，使其经历sn2样反应，从而消除对指导基团的需要。通过适当选择试剂，可以从同一糖基供体开始选择性地合成脱氧糖的非对映体。还将进行核磁共振波谱研究，以了解这些反应的机理。提出的研究可能导致创建一组模块化的试剂组合，以便与广泛的底物轻松构建立体定义的糖苷键。通过精简寡糖结构，该化学将消除因临时假体基的多次液相操作和难以纯化非对映体而产生的化学浪费。因此，它也将为这些分子提供一种更环保的方法。重要的是，从机制研究中获得的见解将指导这些方法在其他类别单糖中的应用。该方法的成功开发将影响需要碳水化合物合成的所有活动领域，包括制药、化学、农业工业以及生物和化学研究界。该项目还将为从本科预科到研究生提供培训，包括来自历史上在科学领域代表性不足的群体的学生。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Clay S. Bennett of the Department of Chemistry at Tufts University will examine the development of methods for the stereoselective construction of deoxy-sugar linkages using shelf stable glycosyl donors. While approaches to deoxy-sugar construction do exist, they frequently rely on the use of temporary directing groups to control selectivity. This introduces multiple additional steps in their synthesis. The proposed research will involve developing a set of reagents to activate deoxy-sugar donors in such a fashion that they undergo SN2-like reactions, thereby eliminating the need for directing groups. Through proper choice of reagent it will be possible to selectively synthesize either diastereomer of a deoxy-sugar starting from the same glycosyl donor. Nuclear magnetic resonance spectroscopy studies directed at understanding the mechanism of these reactions will also be undertaken. The proposed research could lead to the creation of a modular set of reagent combinations for the facile construction of stereodefined glycosidic linkages with a broad set of substrates. By streamlining oligosaccharide construction, this chemistry will eliminate chemical waste arising from multiple solution-phase manipulations of temporary prosthetic groups and difficult purifications of diastereomers. Thus, it will also provide a more environmentally benign approach to these molecules. Importantly, the insights gained from mechanistic studies will guide the application of these methods to other classes of monosaccharides. Successful development of the methodology will impact all areas of activity that requires carbohydrate synthesis, including the pharmaceutical, chemical, agricultural industries, and the biological and chemical research communities. This project will also provide training for pre-undergraduate through graduate students, including students from groups that are historically underrepresented in the sciences.