New Synthetic Strategies and Technologies

新的合成策略和技术

• 批准号: 0603217
• 负责人: Kyriacos C. Nicolaou
• 金额: --
• 依托单位: The Scripps Research Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0603217&HistoricalAwards=false
• 关键词: New; Synthetic; Strategies; Technologies

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.

该研究项目旨在开发新的合成技术和策略，以构建中间分子和目标分子。优化新发现的酸催化碳-碳键形成和分子内诱导碳-碳键断裂的环裂级联反应序列，并将其应用于超穿孔素和穿孔素的合成。第二种最近发现的反应，导致取代的n -羟基吲哚，也将发展。这些杂环基序构成了生物活性天然产物的重要结构域，如抗生素诺卡那星A和各种药物活性药物。最后，将测试关于通过结构修饰提高IBX（一种高价碘试剂）化学反应性的理论预测。除了一些设计的IBX试剂外，拟议的研究将包括手性版本的这种多功能氧化试剂的合成，以探索不对称合成。通过这个奖项，有机和大分子化学项目支持了Scripps研究所化学系的Kyriacos C. Nicolaou博士的研究。Nicolaou博士正在开发新的合成技术和策略，用于构建中间分子和目标分子，用于包括医学和材料科学在内的几个领域的潜在应用。该项目包括三个相关的主题，每个主题都旨在提高化学合成的工具，并展示其应用和对科学和技术的广泛影响，以及对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圣约翰草成分的合成，圣约翰草被用作治疗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，如抗生素诺卡那星A，也将被探索。最后，关于化学反应性的理论预测将作为有机分子形状选择性氧化研究的起点。这些研究中的每一项都为现代制造业和制药市场日益需要的复杂有机分子的合成提供了新的策略和工具的发展希望。