CAREER: Carbonylation Methodologies and Strategies for Complex Natural Product Synthesis

在这个由化学系化学合成计划资助的职业项目中，普渡大学化学系戴明基教授正在开发用于合成生物活性天然产物的钯催化羰化反应的新方法和策略。本研究的目的是以廉价、丰富的一氧化碳为原料，借助少量的钯催化剂，制备出更先进、更复杂的分子结构。这些新开发的方法和战略简化了重要天然产品的合成，这些产品要么是有机杀虫剂，要么是有希望用于药物发现的先导化合物。这项工作有望推进制备复杂分子结构的科学。该项目以钯催化的使用为中心，并将已知的方法扩展到复杂的天然产物合成。除了培训博士后研究人员、研究生和本科生外，该教育计划还包括向印第安纳州高中科学教师和学生宣传催化和天然产物，以及它们对我们日常生活的影响。烷基钯物种很容易与一氧化碳反应生成反应性的酰基钯物种。在这个项目中，开发了新的反应模式来捕获这些原位生成的酰基-钯物种，以构建复杂而重要的结构，否则很难获得这些结构。具体地说，戴教授正在开发(I)钯催化的串联烷氧酮基化大内酯合成具有抗癌活性的四氢吡喃/四氢呋喃桥联大环内酯，(Ii)钯催化的羰基化Heck大内酯合成具有杀虫活性的稠合大环内酯，以及(Iii)钯催化的C-C键裂解羰基化内酯合成具有抗耐药细菌活性的草内酯。这些综合应用对防治人类疾病和提高农业粮食产量具有潜在的影响。这项研究非常适合对不同群体的学生和学者进行教育和培训。

In this CAREER project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Mingji Dai of the Department of Chemistry at Purdue University is developing new palladium-catalyzed carbonylation methodologies and strategies for the syntheses of bioactive natural products. The goal of this research is to use cheap and abundant carbon monoxide as the starting material to made more advanced and complicated molecular structures with the aid of a small amount of palladium catalyst. These newly developed methodologies and strategies streamline the syntheses of important natural products, which are either organic insecticides or promising lead compounds for drug discovery. This work is expected to advance the science of preparing complicated molecular structures. The project centers on the use of palladium catalysis and extends known methods to complex natural product syntheses. In addition to training postdoctoral researchers, graduate students, and undergraduate students, the educational plan includes outreach to educate Indiana high school science teachers and students about catalysis and natural products, as well as their impact of our everyday lives. Alkyl-palladium species react readily with carbon monoxide to generate reactive acyl-palladium species. In this project, novel reaction modes are developed to trap these in situ generated acyl-palladium species to construct complex and important structures that are otherwise difficult to access. Specifically, Professor Dai is developing (i) palladium-catalyzed tandem alkoxycarbonylative macrolactonization to synthesize tetrahydropyran/tetrahydrofuran-containing bridged macrolides with anticancer activity, (ii) palladium-catalyzed carbonylative Heck macrolactonization to synthesize fused macrolides with insecticidal activity, and (iii) palladium-catalyzed C-C bond cleavage carbonylative lactonizations to synthesize oxaspirolactones with potent activity against drug resistant bacteria. The synthetic applications have the potential impact to combat human diseases and improve agricultural food production. The research is well suited to the education and training of a diverse group of students and scholars.