Supplement: Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis

项目概要/摘要 快速可靠地获取合成衍生的化学结构在许多方面都起着至关重要的作用 生物医学研究。这项建议的基本目标是提供根本性的新战略， 高选择性的键合形成，这将使得能够更快速和有效地获得生物活性化合物 有潜在的治疗价值一套新的反应将开发依赖于硼催化偶联 有机氟和有机硅烷基质。依赖于这种反应性范例的糖基化反应将 与催化剂设计、机理研究和计算评估相结合。稳健方法 其能够有效组装具有高度立体控制和宽官能团糖苷键 耐受性将允许获得任何所需的立体化学结果，同时允许迭代的平台， 复合寡糖的组装。新的后过渡金属催化方法将开发利用 使用硼助催化剂将有机氟与有机硅烷基质连接的框架。方法 其中氟的远距离络合允许离去基团按需活化， 在碳水化合物化学和碳-碳键形成方法学中应用的一般策略。 继上述重点发展新的催化方法，途径，以有效的组装 糖基化结构的研究将为获得新的化学探针提供新的方法， 潜在的治疗剂。这一部分将包括制定新的战略， 碳水化合物和肽、天然产物和复合物的立体选择性糖多样化 合成中间体用于定制复杂的天然存在和合成结构的方法将包括 现有羟基官能团的衍生化或未活化的C-H键的生物催化官能化。这些 这些能力将成为一系列广泛的合作研究的基础，包括发现新的 抗微生物和抗癌治疗剂以及新的化学探针， 生物学问题，如转录激活机制和宿主的酶降解， 膳食低聚糖开发的综合方法代表了很少合并的领域， 化学和生物学：主族元素催化，过渡金属催化，碳水化合物化学， 生物催化独特的多学科视角允许检查无法解决的战略 通过传统的方法。这使得进入生物医学重要结构成为可能， 研究将使它们的生物功能和治疗潜力得到更有效的研究。的 这项研究使生物医学重要结构的改进条目成为可能， 功能和治疗潜力进行更有效的研究。

Project Summary / Abstract Rapid and reliable access to synthetically-derived chemical structures plays an essential role in many aspects of biomedical research. The underlying objective of this proposal is to provide fundamentally new strategies for highly selective bond formations that will enable more rapid and efficient access to biologically active compounds of potential therapeutic value. A suite of new reactions will be developed that rely on the boron-catalyzed coupling of organofluorine and organosilane substrates. Glycosylation reactions that rely on this reactivity paradigm will be developed in concert with catalyst design, mechanistic study, and computational evaluation. Robust methods that enable efficient assembly of glycosidic bonds with high degrees of stereocontrol and broad functional group tolerance will allow access to any desired stereochemical outcome while allowing a platform for iterative assembly of complex oligosaccharides. New late transition metal-catalyzed processes will be developed utilizing the framework of connecting organofluorine with organosilane substrates using boron co-catalysis. Methods where remote complexation of fluorine allows leaving groups to be activated on demand will developed as a general strategy for applications in carbohydrate chemistry and in carbon-carbon bond-forming methodology. Following the above focus on the development of new catalytic methods, approaches to the efficient assembly of glycosylated structures will be pursued to provide new methods for accessing novel chemical probes and potential therapeutic agents. This component will include developing new strategies for accessing rare carbohydrates and for the stereoselective glycodiversification of peptides, natural products, and complex synthetic intermediates. Methods for tailoring complex naturally occurring and synthetic structures will include derivatization of existing hydroxyl functionality or biocatalytic functionalization of unactivated C-H bonds. These capabilities will serve as a foundation for a broad array of collaborative studies including the discovery of new antimicrobial and anticancer therapeutic agents and new chemical probes to provide insight into diverse biological questions such as mechanisms of transcriptional activation and enzymatic degradation of host and dietary oligosaccharides. The synthetic approaches developed represent a merger of rarely combined fields of chemistry and biology: main group element catalysis, transition metal catalysis, carbohydrate chemistry, and biocatalysis. The unique multidisciplinary perspective allows examination of strategies that cannot be addressed by conventional approaches. The improved entries to biomedically important structures made possible by this research will enable their biological function and therapeutic potential to be more efficiently studied. The improved entries to biomedically important structures made possible by this research will enable their biological function and therapeutic potential to be more efficiently studied.