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

化学部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大学化学系的教员。他正在开发新类别的成环反应，以进行复杂的多环分子的高效制备。这项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。研究针对的是那些被分离出来的极少量的天然产品。这些物质在治疗癌症和高血压方面具有重要的生物学用途。该研究项目旨在设计和开发新的反应，为这些生物活性物质的制备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。威廉姆斯实验室在合成有机化学领域提供最先进的培训和指导。威廉姆斯的研究小组由博士后学生、博士后研究员和本科生参与者组成，其中包括许多女性和代表性较低的少数民族。所有个人都会接受培训和指导，以确保未来有机会成为下一代科学家。这项研究计划的目标是开发新的方法，用于在复杂的分子排列中环化高度取代的五元碳环。直接应用寻求设计出具有生物活性的天然产物的简明合成途径。为了实现这些目标，人们正在进行两个方面的研究：阴离子电环化反应和过渡金属催化。正在进行研究，以探索在成环过程中使用戊二烯基碳负离子的有效方法。研究了钯和镍催化的反应，以将交叉偶联过程与通过pi-烯丙基中间体的分子重组联系起来。该研究的另一个方面是研究新的金属催化的环丙叉体系重排反应，以促进环化反应，并应用于生物活性萜类化合物的合成。该项目与化学生物学和药物化学的重要副主题很好地结合在一起。这项研究非常适合各级科学家的教育。威廉姆斯教授的团队处于有利地位，可以为科学界代表性不足的学生提供最高水平的教育和培训。各种外展活动是该项目的一部分。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。

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.