Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products

在化学系化学合成计划的支持下，犹他大学的安德鲁·G·罗伯茨将开发新的合成方法，用于生成复杂的多芳香族化合物和具有生物重要性的天然产物。新的方法包括在构建新的碳-碳键的过程中反复形成碳-氮键和裂解，以产生所需的产品。计划中的研究以基本的有机化学原理为基础。罗伯茨博士和他的研究团队将确定将含氮分子(叔胺)用作组装碳-碳键化合物的模板，这些化合物很难通过其他合成路线获得。这些研究工作将有助于培养多个研究生和博士后水平的现代有机合成实践。计划中的更广泛的影响活动将使化学研究与生产性推广计划相结合，这些计划包括化学可视化研讨会和科学、技术、工程和数学(STEM)的促进努力，通过整合基于有机化学的科学家在二年级有机化学课程中的重点作业。这项研究的科学目标是了解叔胺和胺衍生中间体在涉及碳-氮键断裂的转化中的基本反应活性。为实现这一更广泛的目标所作的努力将建立用于复杂分子合成的胺重排和脱氨基方法。初步研究表明，叔胺可以进行迭代甲基化；重排反应，以形成困难的碳-碳键。拟议的研究将涉及合成逻辑的设计和应用，以制备简单的叔胺底物，使用叔胺模板形成环化反应的碳-碳键，以及模板的重排或脱氨基与目标产品难以访问的碳-碳键的形成。计划中的实验将优化胺甲基化和氨基基团转移化学的反应性，建立对胺重排和脱氨基反应的机理理解，并结合开发的方法来完成重要多环分子和生物活性天然产物的简明合成。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis program in the Division of Chemistry, Andrew G. Roberts of the University of Utah will develop new synthetic methodology for the generation of complex polyaromatic compounds and biologically important natural products. The new methodology involves iterative carbon-nitrogen bond formation and cleavage en route to the construction of new carbon-carbon bonds to generate the desired products. The planned research is grounded in fundamental organic chemistry principles. Dr. Roberts and his research team will establish the use of nitrogen-containing molecules (tertiary amines) as templates for the assembly of carbon–carbon bond-containing compounds that are difficult to obtain by other synthetic routes. These research efforts will serve to train multiple students at the graduate and postdoctoral levels in the practice of modern organic synthesis. The planned Broader Impacts activities will align the chemistry research with productive outreach programs that include chemistry visualization workshops and science, technology, engineering, and mathematics (STEM) promotion efforts through the integration of organic chemistry-based scientist spotlight assignments in a sophomore-level organic chemistry course.The scientific goal of this research is to understand the fundamental reactivity of tertiary amines and amine-derived intermediates in transformations that involve carbon–nitrogen bond cleavages. Efforts toward this broader goal will establish amine rearrangement and deaminative methods for complex molecule synthesis. Preliminary research shows that tertiary amines can undergo iterative methylation; rearrangement reactions to enable the formation of difficult carbon–carbon bonds. The proposed research will involve the design and application of synthesis logic to prepare simple tertiary amine substrates, the use the tertiary amine to template carbon–carbon bond forming cyclization reactions, and rearrangement or deamination of the template with the formation of difficult-to-access carbon–carbon bonds of the target products. The planned experiments will optimize reactivity for amine methylation and ammonium-based group transfer chemistry, establish mechanistic understandings for amine rearrangement and deaminative reactions, and incorporate developed methods to complete concise syntheses of important polycyclic molecules and bioactive natural products.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.