Catalytic Methods for Stereoselective 1,2-Cis Glycosylation

项目摘要 在过去的几十年里，糖科学领域蓬勃发展， 鉴定了许多可能在生物学中发挥关键作用的低聚糖和糖缀合物 广泛的生物过程。对生物体功能的认识的快速增长 碳水化合物引起了越来越多的生物学、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- 确定的生物活性碳水化合物。这促使了合成兴趣的复苏， 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道， 连接，α-和β-寡糖和糖缀合物的催化立体选择性合成 这仍然具有挑战性，只能在有限的条件下实现。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 寻求通过制定一系列可预测的和 通过光氧化还原催化合并的立体选择性α-和β-1，2-顺式糖基化反应 镍催化剂。在每个特定目标中，不同类型的导向基团和配体 将采用附着在镍催化剂上的催化剂，并且将采用一种根本不同的策略。 研究以控制异头选择性。因此，所提出的方法将提供各种 构建具有挑战性的α-和β-1，2-顺式糖苷键的新策略。 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在生物活性寡糖中广泛存在， 糖缀合物所提出的反应是可预测的和立体选择性的， 在温和和操作简单的条件下，无需高级培训。重要的是， 这些新方法具有转变为自动化合成的潜力。

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.