Carbonylation Methodologies and Strategies for Building Complex Chemical Structures

在化学系化学合成项目的支持下，普渡大学的戴明基教授正在开发新的方法，利用一氧化碳作为单碳关键，钯催化剂形成新的键，来制造复杂的、具有重要医学意义的分子。复杂的天然产物和天然产物样分子在药物发现中是不可或缺的。然而，由于其结构复杂，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，通过提供获得这些重要目标的简化方法，有助于解决这一问题。这些研究的成果也正在与合作者分享，以调查其生物学意义。同时，这项工作也被用于教育和培训各种各样的学生和学者。戴教授和他的研究小组正在研究如何生成和拦截酰基钯，以设计快速增加结构复杂性的新反应。这种新的合成方法随后被应用于合成序列，目标是具有潜在理想特性的具有挑战性的天然和非天然产品。在该研究项目的一个分支中，正在研究钯催化的串联碳-碳键裂解和羰基化内酯化转化，以合成融合的双环内酯，包括从草药中使用的植物中分离的复杂的Stemona生物碱。在该项目的一个相关但独特的部分，钯催化羰基大内酯化正在探索合成复杂的大内酯及其衍生物。在该计划的第三部分，钯催化串联羰基环化正在探索，以合成具有共价蛋白修饰潜力的亲电基团的天然产物。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。该奖项反映了美国国家科学基金会的法定使命，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 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.