New Synthetic Strategies and Technologies

该研究计划旨在开发用于构建中间体和目标分子的新合成技术和策略。一个新发现的环化-断裂级联反应序列，包括酸催化的碳-碳键形成，然后分子内诱导的碳-碳键断裂，将被优化，其范围将被扩展并应用于金丝桃素和贯叶连翘酮的合成。第二个最近发现的反应，导致取代的N-羟基吲哚，也将开发。这些杂环基序构成了生物活性天然产物如抗生素诺卡氏素A和各种药物活性剂的重要结构域。最后，将测试有关通过结构修饰增强高价碘试剂IBX化学反应性的理论预测。除了一些设计的IBX试剂外，拟议的研究将包括合成这种多功能氧化剂的手性版本，用于探索不对称合成。有了这个奖项，有机和大分子化学计划将支持Kyriacos C.斯克里普斯研究所化学系的尼古拉说。Nicolaou博士正在开发新的合成技术和策略，用于构建中间体和目标分子，以在包括医学和材料科学在内的多个领域中获得潜在应用。该项目包括三个相关的专题，每个专题的目的都是使化学合成工具更加锋利，并展示其应用及其对科学和技术以及教育和培训的广泛影响。新发现的级联反应序列将被优化并应用于合成圣约翰草的成分，圣约翰草用作神经退行性疾病的民间药物，并有可能作为治疗抑郁症和阿尔茨海默病等疾病的先导化合物。第二个最近发现的反应，导致生物活性天然产物的核心结构基序，如抗生素诺卡氏素A，也将进行探索。最后，关于化学反应性的理论预测将作为研究有机分子择形氧化的起点。这些研究中的每一项都为开发新的策略和工具提供了希望，这些策略和工具用于合成我们现代制造业和制药市场日益需求的复杂有机分子。

This research program is directed at the development of new synthetic technologies and strategies for the construction of intermediate and target molecules. A newly discovered annulation-fragmentation cascade reaction sequence involving acid-catalyzed carbon-carbon bond formation followed by an intramolecularly-induced carbon-carbon bond scission will be optimized, and its scope will be expanded and applied to the synthesis of hyperforin and perforatumone. A second recently discovered reaction, leading to substituted N-hydroxyindoles, will also be developed. These heterocyclic motifs constitute important domains of bioactive natural products like the antibiotic nocathiacin A and of a variety of medicinally active agents. Finally, a theoretical prediction will be tested regarding enhancement through structural modifications of the chemical reactivity of IBX, a hypervalent iodine reagent. In addition to a number of designed IBX reagents, the proposed research will encompass the synthesis of chiral versions of this versatile oxidizing reagent for explorations in asymmetric synthesis.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Kyriacos C. Nicolaou, of the Department of Chemistry at the Scripps Research Institute. Dr. Nicolaou is developing new synthetic technologies and strategies for the construction of intermediate and target molecules for potential applications in several areas, including medicine and materials science. The project encompasses three related topics, each aiming to sharpen the tools of chemical synthesis and demonstrate their application and broad impact on science and technology on one hand and education and training on the other. A newly discovered cascade reaction sequence will be optimized and applied to the synthesis of constituents of St. Johns Wort, used as a folk medicine for neurodegenerative disorders and having potential as lead compounds for treatment of diseases such as depression and Alzheimers disease. A second recently discovered reaction, leading to the core structural motifs of bioactive natural products like the antibiotic nocathiacin A, will also be explored. Finally, a theoretical prediction regarding chemical reactivity will serve as the starting point for a study of the shape-selective oxidation of organic molecules. Each of these studies offers promise for the development of new strategies and tools for the synthesis of the complex organic molecules increasingly demanded by our modern manufacturing and pharmaceutical markets.