Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

在化学系化学合成计划的支持下，埃默里大学戴明基教授正在开发新的催化反应，利用廉价和可持续的一氧化碳作为一碳关键，制造复杂的和医学上重要的分子。天然产物是现代药物化学发展中不可缺少的物质。然而，天然稀缺性和许多有希望的天然产物的化学结构的复杂性是其作为潜在的药物制剂进行充分探索和开发的主要障碍。戴教授和他的研究小组正在研究的反应，通过提供简化和可持续的方法来制造重要的天然产品和相关分子，正在帮助解决这个问题。这些研究的产品也与合作者分享，以调查它们的生物学意义，包括抗癌活性。戴教授还为不同的博士后研究人员、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准备。戴教授和他的研究团队正在研究过渡金属催化的创新羰化反应，以快速建立结构复杂性。然后，这些新的方法被应用于合成序列，目标是挑战具有理想特征的天然和非天然产品，用于医学研究。在该研究计划的一个分支中，正在开发和利用钯催化的羰基化转化，以从草药中使用的植物合成复杂的多环抗癌天然产品。在该项目的一个相关但不同的部分，努力将重点放在用镍催化取代上述钯，以开发更经济和可持续的工艺，以及使不同的羰基化内酯能够合成各种内酯及其衍生物。在该计划的第三部分，正在探索新的过渡金属催化的碳化大内酯反应，以合成复杂的大环内酯类化合物及其衍生物。该计划承诺开发天然产物合成和精制的新模式，在合成、化学生物学和药物化学方面具有广泛的潜在影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.