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基团 操作以实现选择性反应结果。需要新的、有选择性的方法， 吡喃糖和呋喃糖的合成。该提案描述了选择性自由基的发展 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，C-C键形成反应， 自由基重排，以实现糖异构体、支链糖的广泛合成， 脱氧糖，分别。使用最先进的合成，机械和理论工具，我们的 方法包括识别新的催化策略，以控制键断裂，键形成， 在复杂聚糖分子框架内的自由基重组步骤。成功 这项研究的进展预计将改变碳水化合物的合成， 获取这些复杂药效团所需的时间和资源。基本机制发现 在实现这一目标的过程中发现的，预计将进一步有助于我们对 碳水化合物的反应模式和奠定基础的催化方法，选择性自由基 更广泛地说，功能化反应。

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, the synthesis of rare and unnatural sugars requires multistep chemical synthesis, and commonly relies 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, C-C bond forming reactions, and radical rearrangements to achieve broad synthetic access to sugar isomers, branched-chain sugars, 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.