Catalytic Methods for Stereoselective 1,2-Cis Glycosylation

项目概要 糖科学领域在过去几十年中蓬勃发展，导致 鉴定许多寡糖和糖复合物，它们可以在 广泛的生物过程。关于功能的知识的快速增长 碳水化合物越来越受到生物学、药理学和医学的关注 研究人员。满足他们的研究需求需要获得大量的良好资源 定义的生物活性碳水化合物。这促使人们对合成兴趣的复兴， 特别关注糖苷键的新方法。 即使有大量关于立体选择性构建糖苷的优雅报告 α-和β-低聚糖和复合糖的连接、催化立体选择性合成 仍然具有挑战性，并且只有在有限的条件下才能实现。一 历史上被证明具有挑战性的糖苷键是β-甘露糖苷键。这个提议 力求通过开发一系列可预测和可满足的需求来解决这一未满足的需求 通过光氧化还原催化的合并进行立体选择性α-和β-1,2-顺式糖基化反应 用镍催化。在每个具体目标中，不同类型的导向基团和配体 将采用附着在镍催化剂上的方法，并且将采用根本不同的策略 研究控制异头选择性。因此，所提出的方法将提供多种 构建具有挑战性的α-和β-1,2-顺式糖苷键的新策略。 所提出的通过双重催化的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在生物活性寡糖中广泛存在，并且 糖复合物。所提出的反应是可预测的、立体选择性的并进行 在温和且操作简单的条件下进行，无需高级培训。重要的是， 新方法有可能转化为自动化合成。

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.