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: 2349014
• 负责人: Mingji Dai
• 金额: $ 57.5万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2349014&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 Emory University is developing new catalytic reactions to make complex and medicinally important molecules using cheap and sustainable carbon monoxide as a one-carbon linchpin. Natural products are indispensable in the development of modern medicinal chemistry. However, the natural scarcity and the complexity of the chemical structures of many promising natural products are major hurdles to their scale-up for full exploration and exploitation as potential pharmaceutical agents. The reactions that Professor Dai and his research group are investigating are helping to address this problem by providing streamlined and sustainable ways to make important natural products and related molecules. The products of these studies are also being shared with collaborators to investigate their biological significance, including anticancer activity. Professor Dai is also providing valuable training to a diverse group of postdoctoral researchers, graduate students, and undergraduate students and preparing these individuals for future careers in the chemical sciences.Professor Dai and his research team are investigating innovative carbonylation reactions with transition metal catalysis to rapidly build structural complexity. These new methodologies are then being applied in synthetic sequences targeted toward challenging natural and non-natural products with desirable characteristics for medicinal studies. In one branch of the research program, enabling palladium-catalyzed carbonylative transformations are being developed and utilized to synthesize complex and polycyclic anticancer natural products from plants used in herbal medicine. In a related but distinct part of the project, efforts will be focused on replacing the aforementioned palladium with nickel catalysis to both develop more economical and sustainable processes as well as to enable different carbonylative lactonizations to synthesize various lactones and their derivatives. In the third portion of the program, new transition metal-catalyzed carbonylative macrolactonization reactions are being explored to synthesize complex macrolides and their derivatives. The program promises to develop new modalities toward natural product synthesis and elaboration with broad potential impact in synthesis, chemical biology and medicinal chemistry.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.

在化学合成计划中的支持下，埃默里大学的Mingji Dai教授正在开发新的催化反应，以使用便宜且可持续的一氧化碳作为一碳Linchpin，从而制造复杂且具有医学上重要的分子。天然产品对于现代药物化学的发展是必不可少的。但是，许多有前途的天然产品的自然稀缺性和化学结构的复杂性是其扩大障碍的主要障碍，以全面探索和剥削作为潜在的药物。 Dai教授及其研究小组正在调查的反应正在通过提供简化且可持续的方法来制造重要的天然产品和相关分子来帮助解决这一问题。这些研究的产物也与合作者共享，以研究其生物学意义，包括抗癌活性。 Dai教授还为多样化的博士后研究人员，研究生和本科生提供了宝贵的培训，并为这些人在化学科学领域的未来职业做准备。然后以合成序列应用这些新方法，该序列针对挑战自然和非天然产物具有可取的药物研究特征。在该研究计划的一个分支中，正在开发和利用启用钯催化的羰基转化，以合成从草药中使用的植物的复合物和多晶抗癌天然产物。在该项目的相关但独特的部分中，将努力用镍催化代替上述钯，以开发更经济和可持续的过程，并能够使不同的羰基乳酸化合成各种lactones及其衍生物。在该程序的第三部分中，正在探索新的过渡金属催化的大分裂反应，以合成复杂的大花环及其衍生物。该计划有望开发出新的模式，以在合成，化学生物学和药物化学中具有广泛的潜在影响，以实现自然产品的合成和精心设计。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力优点和更广泛的影响来通过评估来支持的。