CAREER: Carbonylation Methodologies and Strategies for Complex Natural Product Synthesis

职业：复杂天然产物合成的羰基化方法和策略

• 批准号: 1553820
• 负责人: Mingji Dai
• 金额: $ 65万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553820&HistoricalAwards=false
• 关键词: CAREER; Carbonylation; Methodologies; Strategies; Complex

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.

普渡大学化学系的戴明吉教授在化学部化学合成项目资助的CAREER项目中，正在开发新的钯催化羰基化方法和合成生物活性天然产物的策略。 本研究的目的是以廉价、丰富的一氧化碳为起始原料，在少量钯催化剂的辅助下，制备出更高级、更复杂的分子结构。 这些新开发的方法和策略简化了重要天然产物的合成，这些天然产物是有机杀虫剂或有前途的药物发现先导化合物。 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，教育计划包括外展教育印第安纳州高中科学教师和学生关于催化和天然产物，以及他们对我们日常生活的影响。 烷基-钯物质容易与一氧化碳反应以生成反应性酰基-钯物质。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，以构建复杂和重要的结构，否则难以访问。具体而言，戴教授正在开发（i）钯催化的串联烷氧基羰基化大环内酯化反应，以合成具有抗癌活性的含四氢吡喃/四氢呋喃的桥接大环内酯，（ii）钯催化的羰基化Heck大环内酯化反应，以合成具有杀虫活性的稠合大环内酯，以及（iii）钯催化的C-C键断裂羰基化内酯化反应，以合成具有有效抗耐药性细菌活性的氧杂螺内酯。 合成应用对防治人类疾病和改善农业粮食生产具有潜在影响。这项研究非常适合于教育和培训不同群体的学生和学者。