Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

在化学系化学合成项目的支持下，埃默里大学的戴明吉教授正在开发新的催化反应，利用廉价且可持续的一氧化碳作为一碳关键，制造复杂且具有医学重要性的分子。天然产物是现代药物化学发展不可缺少的组成部分。然而，许多有前途的天然产品的天然稀缺性和化学结构的复杂性是其扩大规模以充分探索和开发为潜在药剂的主要障碍。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物和相关分子，有助于解决这一问题。这些研究的产品也正在与合作者分享，以研究其生物学意义，包括抗癌活性。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，为这些人未来在化学科学领域的职业生涯做好准备。戴教授和他的研究团队正在研究利用过渡金属催化的创新羰基化反应，以快速构建结构复杂性。这些新方法随后被应用于针对具有医学研究所需特性的具有挑战性的天然和非天然产品的合成序列。在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来从草药中使用的植物合成复杂的多环抗癌天然产物。在该项目的一个相关但独特的部分中，努力将集中在用镍催化剂取代上述钯，以开发更经济和可持续的工艺，并使不同的羰基化内酯化反应能够合成各种内酯及其衍生物。在第三部分的计划，新的过渡金属催化羰基化大环内酯化反应正在探索合成复杂的大环内酯及其衍生物。该计划承诺开发天然产物合成和精细化的新模式，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知识价值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.