Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products

将胺转化为复杂的多环分子和生物活性天然产物

• 批准号: 2247651
• 负责人: Andrew Roberts
• 金额: $ 55万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247651&HistoricalAwards=false
• 关键词: Transforming; Amines; into; Complex; Polycyclic

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.

在化学系化学合成项目的支持下，Andrew G.犹他州大学的罗伯茨将开发新的合成方法，用于生成复杂的多环芳香族化合物和具有生物重要性的天然产物。这种新方法包括反复的碳-氮键形成和裂解，以构建新的碳-碳键，从而产生所需的产物。计划中的研究以基本有机化学原理为基础。Roberts博士和他的研究团队将建立使用含氮分子（叔胺）作为模板，用于组装通过其他合成途径难以获得的含碳-碳键的化合物。这些研究工作将有助于在现代有机合成实践中培养研究生和博士后水平的多名学生。计划中的更广泛影响活动将使化学研究与富有成效的外联计划保持一致，包括化学可视化研讨会和科学，技术，工程，和数学（STEM）的促进工作，通过有机化学为基础的科学家聚光灯任务的整合在一个小学生水平的有机化学课程。这项研究的科学目标是了解叔胺和胺的基本反应性-涉及碳-氮键断裂的转化中的衍生中间体。为了实现这一更广泛的目标，将建立胺重排和脱氨基的方法来合成复杂的分子。初步研究表明，叔胺可以进行反复甲基化;重排反应，使困难的碳-碳键的形成。拟开展的研究将涉及设计和应用合成逻辑制备简单的叔胺底物，利用叔胺模板碳碳键形成环化反应，以及模板的重排或脱氨与难以进入的碳碳键形成目标产物。计划中的实验将优化胺甲基化和基于铵的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，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的评估来支持。影响审查标准。