Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

构建复杂化学结构的羰基化方法和策略

• 批准号: 2102022
• 负责人: Mingji Dai
• 金额: $ 50万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102022&HistoricalAwards=false
• 关键词: Carbonylation; Methodologies; Strategies; Building; Complex

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Mingji Dai of Purdue University is developing new ways to make complex and medicinally important molecules using carbon monoxide as a one-carbon linchpin and a palladium catalyst to form new bonds. Complex natural products and natural product-like molecules are indispensable in drug discovery. However, their structural complexity necessitates the development of new catalytic synthetic methods for their synthesis. The reactions that Professor Dai and his research group are investigating are helping to address this problem by providing streamlined methods to access these important targets. The products of these studies are also being shared with collaborators to investigate their biological significance. Simultaneously, this work is being used for the education and training of a diverse group of students and scholars.Professor Dai and his research team are investigating how to generate and intercept acyl-palladium species to design new reactions that rapidly increase structural complexity. This new synthetic methodology is then being applied in synthetic sequences that target challenging natural and non-natural products with potentially desirable characteristics for medicinal studies. In one branch of the research program, transformations involving palladium-catalyzed tandem carbon-carbon bond cleavage and carbonylative lactonization are being studied to synthesize fused bicyclic lactones including complex Stemona alkaloids isolated from plants used in herbal medicine. In a related but distinct part of the project, palladium-catalyzed carbonylative macrolactonization is being explored to synthesize complex macrolides and their derivatives. In the third portion of the program, palladium-catalyzed tandem, carbonylative cyclization is being explored to synthesize natural products that feature electrophilic moieties with the potential for covalent protein modification. Professor Dai is also providing valuable training to postdoctoral researchers, graduate students, and undergraduate students and preparing these individuals for future careers in the chemical sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学合成项目的支持下，普渡大学的戴明吉教授正在开发新的方法，利用一氧化碳作为一个碳的关键和钯催化剂形成新的键，来制造复杂的和医学上重要的分子。复杂天然产物和类天然产物分子是药物发现中不可缺少的组成部分。然而，它们的结构复杂性需要开发新的催化合成方法来合成它们。戴教授和他的研究小组正在研究的反应通过提供简化的方法来访问这些重要目标，有助于解决这个问题。这些研究的成果也正在与合作者分享，以研究其生物学意义。同时，这项工作也被用于教育和培训不同的学生和学者。戴教授和他的研究团队正在研究如何生成和拦截酰基钯物种，以设计新的反应，迅速增加结构的复杂性。然后，这种新的合成方法被应用于合成序列中，这些合成序列针对具有潜在理想特性的具有挑战性的天然和非天然产品进行药物研究。在研究计划的一个分支中，正在研究涉及钯催化的串联碳-碳键断裂和羰基化内酯化的转化以合成稠合双环内酯，包括从草药中使用的植物中分离的复杂的百部生物碱。在该项目的一个相关但不同的部分中，正在探索钯催化的羰基化大环内酯化来合成复杂的大环内酯及其衍生物。在该计划的第三部分，钯催化的串联，羰基环化正在探索合成天然产物，功能亲电部分与共价蛋白质修饰的潜力。戴教授还为博士后研究人员、研究生和本科生提供有价值的培训，并为这些人未来在化学科学领域的职业生涯做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Flow Chemistry-Enabled Divergent and Enantioselective Total Syntheses of Massarinolin A, Purpurolides B, D, E, 2,3-Deoxypurpurolide C, and Structural Revision of Massarinolin A.

• DOI: 10.1002/anie.202109625
• 发表时间: 2021-11-15
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Wang YC;Cui C;Dai M
• 通讯作者: Dai M