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

化学系的化学合成计划支持大卫威廉姆斯教授的项目。 威廉姆斯教授是印第安纳州大学化学系的教员。 他正在开发新型的成环反应，以高效制备复杂的多环分子。 该研究的目标是开发新的反应和简洁的策略，允许快速构建包含多个环的物质。 研究针对的是已经以极少量分离的天然产物。 这些物质具有治疗癌症和高血压的重要生物学用途。 该研究项目旨在设计和开发新的反应，为制备这些生物活性物质提供有效的合成途径。 这项研究从根本上推动了化学作为药物发现平台的发展。 威廉姆斯实验室提供合成有机化学领域最先进的培训和指导。 威廉姆斯的研究小组由博士前学生、博士后研究员和本科生组成，其中包括许多女性和代表性不足的少数民族。 所有人都接受培训和指导，以确保未来成为下一代科学家的机会。该研究计划的目标是开发新的方法，用于复杂分子排列中高度取代的五元碳环的成环。 寻求直接应用，以设计简洁的合成途径，以生物活性的天然产物。 为了实现这些目标，人们正在进行两条研究路线：阴离子电环化反应和过渡金属催化。 目前正在进行研究，以探索使碳负离子参与成环过程的有效方法。 研究了钯和镍催化的反应，以通过π-烯丙基中间体将交叉偶联过程与分子重组联系起来。研究的另一个方面是研究新的金属催化的应变亚环丙基系统的重排，以推进应用于生物活性萜烯合成的成环反应。 该项目与化学生物学和药物化学的重要子课题有很好的联系。 这项研究非常适合各级科学家的教育。 威廉姆斯教授的小组有能力为科学领域代表性不足的学生提供最高水平的教育和培训。 各种外联活动是该项目的一部分。这些科学成果的更广泛影响通过使新药的发现而使社会受益。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor David Williams. Professor Williams is a faculty member in the Department of Chemistry at Indiana University. He is developing new classes of ring-forming reactions to carry out highly efficient preparations of complex, polycyclic molecules. The goal of the research is to develop new reactions and concise strategies that permit the rapid construction of substances that incorporate multiple rings. Studies are directed to natural products that have been isolated in extremely small quantities. These substances have important biological uses for treatment of cancer and hypertension. This research project seeks to design and develop new reactions that provide efficient synthetic pathways for the preparation of these bioactive substances. This research fundamentally advances chemistry as a platform for drug discovery. The Williams laboratory offers state-of-the-art training and mentoring in the field of synthetic organic chemistry. A blend of predoctoral students, postdoctoral fellows, and undergraduate participants, including many women and underrepresented minorities, make up the Williams' research group. All individuals receive training and mentoring to enable future opportunities as next-generation scientists. The goal of this research program is to develop new methodologies for the annulation of highly substituted, five-membered carbocycles in complex molecular arrangements. Direct applications are sought to devise concise synthetic pathways to bioactive natural products. Two lines of investigation are being pursued to achieve these goals: anionic electrocyclization reactions and transition metal catalysis. Studies are underway to explore effective methods to engage pentadienyl carbanions in ring-forming processes. Palladium and nickel-catalyzed reactions are studied to link cross-coupling processes with molecular reorganization via pi-allyl intermediates. Another aspect of the research investigates new metal-catalyzed rearrangements of strained cyclopropylidene systems to advance annulation reactions that are applied to the synthesis of bioactive terpenes. The project interfaces well with important subtopics in chemical biology and medicinal chemistry. The research is well suited for the education of scientists at all levels. Professor Williams' group is well positioned to provide the highest level of education and training for students underrepresented in science. A variety of outreach activities are part of the project. The broader impact of these scientific results benefit society by enabling the discovery of new pharmaceuticals.