Catalytic Methods for Stereoselective 1,2-Cis Glycosylation

项目总结 糖科学领域在过去的几十年里蓬勃发展，导致了 鉴定了许多低聚糖和糖共轭化合物，它们可能在 广泛的生物过程。关于细胞因子功能的知识的快速增长 碳水化合物越来越受到生物学、药理学和医药学的关注。 研究人员。满足他们的研究需求需要获得大量的油井- 定义生物活性碳水化合物。这促使合成兴趣卷土重来， 特别关注糖苷键的新方法。 即使有大量关于立体选择性结构的优雅报告 α-和β-寡糖及其糖偶联物的连接、催化立体选择性合成 仍然具有挑战性，只有在有限的条件下才能实现。一 历史上证明具有挑战性的糖苷键是β-甘露糖苷键。这项建议 寻求通过开发一系列可预测和 光氧化还原催化的立体选择性α-和β-1，2-顺式糖基化反应 以镍为催化剂。在每个特定的目标中，不同类型的导向基团和配体 将使用附着式镍催化剂，并将采用一种根本不同的策略 研究以控制异构体的选择性。因此，拟议的方法将提供各种 构建具有挑战性的α-和β-1，2-顺式糖苷键的新策略。 所提出的双催化立体选择性糖基化反应具有重要意义。 因为这些类型的糖苷键广泛存在于生物活性寡糖和 糖偶联物。建议的反应是可预测的、立体选择性的和进行的。 在温和和操作简单的条件下，不需要高级培训。重要的是 新方法有可能转变为自动合成。

PROJECT SUMMARY The field of glycoscience has burgeoned in the last several decades, leading to the identification of many oligosaccharides and glycoconjugates which could serve critical roles in a wide range of biological processes. This rapid growth of knowledge about the function of carbohydrates has attracted increasing attention from biological, pharmacological, and medicinal researchers. Meeting their research demands require access to significant quantities of well- defined bioactive carbohydrates. This has prompted resurgence in synthetic interest, with a particular focus on new approaches to the glycosidic bond. Even with the abundance of elegant reports for stereoselective construction glycosidic linkages, catalytic stereoselective synthesis of α- and β-oligosaccharides and glycoconjugates remains challenging and can only be achieved in the context of a limited set of conditions. One of glycosidic bonds that has historically proven challenging is β-mannosidic bond. This proposal seeks to address this unmet need through the development of a series of predictable and stereoselective α- and β-1,2-cis glycosylation reactions via the merger of photoredox catalysis with nickel catalysis. In each Specific Aim, a different type of directing groups and ligands attached to nickel catalyst will be employed, and a fundamentally different strategy will be investigated to control anomeric selectivity. As such, the proposed methods will provide a variety of new strategies for the construction of challenging α- and β-1,2-cis glycosidic bonds. The proposed stereoselective glycosylation reactions via dual catalysis are significant because these type of glycosidic bonds are widely prevalent in bioactive oligosaccharides and glycoconjugates. The proposed reactions are predictable and stereoselective and conducted under mild and operationally simple conditions without requiring advanced training. Importantly, the new methods have the potential for transforming into automated synthesis.