Selective Catalytic Strategies for Carbohydrate Synthesis

碳水化合物合成的选择性催化策略

基本信息

批准号：
10589062
负责人：
Alison Wendlandt
金额：
$ 29.27万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2026-01-31
项目状态：
未结题

项目摘要

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.

项目摘要稀有和不自然的碳水化合物在数百种生物活性的效力和选择性中起着至关重要的作用天然产品和药物化合物。这些脚手架通常具有异常的相对/绝对立体化学，吡喃糖/呋喃糖环分支，杂原子取代和不同程度的脱氧。尽管稀有糖和不自然糖具有生物学意义，但合成挑战限制了进入这些重要分子。由于其功能组密度和立体化学复杂性，电流稀有糖和不自然糖的合成需要多步化学合成，并且通常依赖于保护小组操纵以实现选择性反应结果。需要新的选择性方法吡喃糖和呋喃糖糖的权宜合成。该建议描述了选择性的发展自由基反应将未受保护和最小保护的碳水化合物转化为多样化的碳水化合物单糖和聚糖。我们专门针对表达反应和根治性重排分别获得广泛的合成访问稀有异构体和去氧糖。使用最新的合成，机械和理论工具，我们的方法涉及确定新的催化策略在复杂的聚糖背景下控制键断裂，形成键和自由基的重组步骤分子框架。预计这项拟议研究的成功发展将改变碳水化合物合成，大大减少了访问这些复杂所需的时间和资源药剂团。在实现这一目标的途中揭示了基本的机理发现将进一步预期为我们对碳水化合物反应性模式的理解做出重大贡献，并为更广泛的选择性自由基官能化反应的催化方法。