Advances of Methodology and Design for the Synthesis of Complex Polycyclic Natural Products

这项由美国国家科学基金会化学部化学催化计划资助的项目研究有机金属化合物，以发现新的反应方法和反应性。寻求这些进展是为了简化复杂分子快速组装的化学途径的效率。这些努力的一个关键方面是寻求确定构建生物活性化合物的通用、高价值的方法，以创建一个药物化学研究的平台。研究的具体方面考察了涉及铁、铟和钯的络合物的新反应的发展。这些研究应用于天然产物的合成，这些天然产物对各种癌症和炎症疾病模型显示出良好的生物活性。由于目前科学的局限性，本研究中提出的天然产物以前并没有通过合成来制备。因此，这一计划的成功将推动这些物质作为潜在的类药物分子的设计和研究。这项研究的一个目标是为通常有用的交叉偶联反应创造新的方法，以产生化学反应活性的联烯，并设计新的碳环化反应。这些努力直接应用于合成瑞香环素和四酮类天然产物，但也具有更广泛的适用性。这个大学实验室提供合成有机化学领域最先进的培训和指导，具有重要的多样性计划。博士后学生、博士后研究员和本科生参与者的混合强调纳入女性和代表性不足的少数民族。所有人都会接受培训和指导，以便将来有机会成为下一代的顶尖科学家。这些科学成果的更广泛影响使新药物的发现成为可能，从而使社会受益。

This project funded by the Chemical Catalysis program of the Chemistry Division of the NSF investigates organometallic complexes in order to discover new reaction methods and reactivity. These advances are sought in order to streamline the efficiencies of chemical pathways for the rapid assembly of complex molecules. A key aspect of these efforts seeks to define versatile, high-value methods for the construction of bioactive compounds to create a platform for studies of medicinal chemistry. Specific aspects of the research examine the development of new reactions involving complexes of iron, indium and palladium. These studies are applied in the synthesis of natural products which display promising bioactivity toward various cancers and disease models of inflammation. Because of current limitations of the science, the natural products proposed in this investigation have not been previously prepared by synthesis. Therefore, success in this program is advancing the design and study of these substances as potential drug-like molecules. A goal of this research is to create new methodologies for generally useful cross-coupling reactions to produce chemically reactive allenes, and to design new carbocyclization reactions. These efforts are directly applied toward the synthesis of daphnicyclidin and tetrapetalone natural products, but also have broader applicability.This University laboratory offers state-of-the-art training and mentoring in the field of synthetic organic chemistry with a significant diversity program. A blend of predoctoral students, postdoctoral fellows, and undergraduate participants emphasizes the inclusion of women and underrepresented minorities. All individuals receive training and mentoring to enable future opportunities as leading scientists of the next generation. The broader impact of these scientific results benefit society by enabling the discovery of new pharmaceuticals.