Selective Catalytic Strategies for Carbohydrate Synthesis

项目摘要 稀有和非天然碳水化合物在数百种生物活性物质的效力和选择性中起着至关重要的作用。 天然产物和药物化合物。这些支架通常具有不寻常的相对/绝对 立体化学、吡喃糖/呋喃糖环支化、杂原子取代和不同程度的 脱氧尽管稀有和非天然糖具有生物学意义，但合成挑战限制了获取 这些重要的分子。由于它们的官能团密度和立体化学复杂性， 稀有和非天然糖的合成需要多步化学合成，并且通常依赖于保护 群体操作以实现选择性反应结果。需要新的、有选择性的方法， 吡喃糖和呋喃糖的适宜合成。该提案描述了选择性的发展 将未保护的和最低限度保护的碳水化合物转化为二硫键官能化的 单糖和聚糖。我们专门针对差向异构化反应和自由基重排， 分别实现了对稀有异构体和脱氧糖的广泛合成。使用最先进的 合成，机械和理论工具，我们的方法涉及新的催化策略的识别 控制复合聚糖中的键断裂、键形成和自由基重组步骤 分子框架这项拟议研究的成功开发预计将改变 碳水化合物的合成，大大减少了时间和资源所需的访问这些复杂的 药效团在实现这一目标的过程中发现的基本机制研究结果， 大大有助于我们理解碳水化合物的反应模式，并奠定了基础， 更广泛地说，是选择性自由基官能化反应的催化方法。

Project Summary Rare and unnatural carbohydrates play an essential role in the potency and selectivity of hundreds of bioactive natural products and pharmaceutical compounds. These scaffolds often feature unusual relative/absolute stereochemistry, pyranose/furanose ring branching, heteroatom substitutions, and varying degrees of deoxygenation. Despite the biological significance of rare and unnatural sugars, synthetic challenges limit access to these important molecules. Due to their functional group density and stereochemical complexity, current syntheses of rare and unnatural sugars require multistep chemical synthesis, and commonly rely on protecting group manipulations to achieve selective reaction outcomes. New, selective methods are needed for the expedient synthesis of pyranose and furanose sugars. This proposal describes the development of selective radical reactions to transform unprotected and minimally protected carbohydrates into diversely functionalized monosaccharides and glycans. We specifically target epimerization reactions and radical rearrangements to achieve broad synthetic access to rare isomeric and deoxygenated sugars, respectively. Using state-of-the-art synthetic, mechanistic and theoretical tools, our approach involves the identification of new catalytic strategies to control bond breaking, bond forming, and radical reorganization steps within the context of complex glycan molecular frameworks. The successful development of this proposed research is anticipated to transform carbohydrate synthesis, dramatically reducing the time and resources necessary to access these complex pharmacophores. Fundamental mechanistic findings revealed en route to this goal are further anticipated to contribute significantly to our understanding of carbohydrate reactivity patterns and to lay the groundwork for catalytic approaches to selective radical functionalization reactions, more broadly.