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.

在化学部化学综合计划资助的这个职业项目中，普渡大学化学系的Mingji Dai教授正在开发新的钯催化的羰基化方法和生物活性天然产品合成的策略。 这项研究的目的是将廉价且丰富的一氧化碳用作起始材料，从而借助少量钯催化剂，使得更先进和复杂的分子结构。 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铅化合物。 预计这项工作将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，教育计划还包括向印第安纳高中科学教师和学生提供有关催化和天然产品的教育以及对我们日常生活的影响。 烷基 - 钯物种与一氧化碳易于反应，产生反应性酰基 - 帕拉德菌种。在这个项目中，开发了新的反应模式来捕获这些原位产生的酰基 - 钯物种，以构建原本难以进入的复杂而重要的结构。具体而言，DAI教授正在开发（i）钯催化的串联烷氧基钙化大分子化，以合成四氢吡喃/四氢呋喃的桥梁桥梁的抗癌物活性，（II）与胶原蛋白的合成粉丝分裂的粉丝分裂的毛酸果酸酯纤维素化的麦克罗果质细胞调解，杀虫活性和（iii）钯催化的C-C键裂解羰基乳酸化，以对抗药性细菌的有效活性合成氧曲甲基酮。 合成应用对打击人类疾病并改善农业粮食生产有潜在的影响。这项研究非常适合对各种学生和学者组的教育和培训。