Development of New Catalytic Reactions for the Synthesis of Natural Products

在化学系化学合成（SYN）项目的支持下，加州理工学院（Caltech）的Sarah E. Reisman教授正在开发用于天然产物化学合成的新催化反应。推进化学合成科学的关键是设计和应用碳-碳（C-C）键形成的新反应。新的催化C-C键形成反应的发明使化学家能够以更高的效率合成重要的分子，从而降低了成本和所需的资源。Reisman和团队将专注于天然产物的合成，特别是所选目标分子的复杂结构对当前最先进的催化技术提出了挑战，并提供了一个平台来发明、测试和改进新的C-C键形成反应，最终可以在广泛的分子合成中找到应用，从而造福社会。在构建有机分子的理论、方法和策略方面对科学家进行严格的培训将是资助研究的重要组成部分。本科生、研究生和博士后研究人员将在化学、生物技术和材料科学领域接受培训。在加州理工学院教学、学习和推广中心（CTLO）的支持下，Reisman团队将访问洛杉矶联合学区（LAUSD）和帕萨迪纳联合学区（PUSD）的教室，向高中理科学生介绍化学在药物发现中的作用和相关的化学职业机会。Reisman团队将与当地酿酒厂Progress Brewing合作，举办以加州理工学院科学家为特色的科学咖啡馆项目。结构复杂的多环天然产物-通常具有多个反应官能团和立体中心-挑战了当前合成方法的极限。该奖项将支持两个以新反应开发为特色的天然产物合成项目。第一个项目将研究镍催化的交叉偶联，作为简洁和模块化合成一种天然产物的关键步骤。第二个项目将开发一种利用光氧化还原催化制备聚酮天然产物的自由基-极性交叉环。预计这些研究将推动催化C-C键形成的最新技术，为复杂环境下的策略键形成提供新的工具，并展示现代合成方法如何改善合成策略。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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 (SYN) program in the Division of Chemistry, Professor Sarah E. Reisman of the California Institute of Technology (Caltech) is developing new catalytic reactions for the chemical synthesis of natural products. Key to advancing the science of chemical synthesis is the design and application of new reactions for carbon–carbon (C–C) bond formation. The invention of new catalytic C–C bond forming reactions allows chemists to synthesize important molecules with increased efficiency – reducing the cost and resources required. Reisman and team will focus on the synthesis of natural products and, in particular, the complex structures of the selected target molecules pose challenges to the current state-of-the-art in catalysis, and provide a platform to invent, test, and refine new C–C bond forming reactions that can ultimately find applications in the synthesis of a broad range of molecules that can benefit society. The rigorous training of scientists in the theory, methods, and strategies of constructing organic molecules will be an essential part of the funded research studies. Undergraduate, graduate student and post-doctoral researchers trained through this research experience will be poised to pursue careers in the chemical, biotechnology, and materials science sectors. With support from the Caltech Center for Teaching, Learning and Outreach (CTLO), the Reisman team will visit Los Angeles Unified School District (LAUSD) and Pasadena Unified School District (PUSD) classrooms to give presentations to high school science students about the role of chemistry in drug discovery and related chemistry career opportunities. In partnership with Progress Brewing, a local brewery, the Reisman team will host Science Café programs featuring Caltech scientists.Structurally complex, polycyclic natural products – which often possess multiple reactive functional groups and stereogenic centers – challenge the limits of current synthetic methodology. This award will support two natural product synthesis projects that feature new reaction development. The first project will investigate a Ni-catalyzed cross-coupling as the key step in a concise and modular synthesis of an ent-kauranoid natural product. The second project will develop a radical-polar crossover annulation using photoredox catalysis to prepare a polyketide natural product. It is expected that these studies will advance the state of the art in catalytic C–C bond formation, provide new tools for strategic bond formation in complex settings, and demonstrate how modern synthetic methods can improve synthetic strategy.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.