Sulfonimidamides: New Frontiers in Stereochemistry and Functionality

磺酰亚胺：立体化学和功能性的新领域

• 批准号: 2247324
• 负责人: Jared Shaw
• 金额: $ 57.5万
• 依托单位: University of California-Davis
• 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: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247324&HistoricalAwards=false
• 关键词: Sulfonimidamides; New; Frontiers; Stereochemistry; Functionality

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Jared T. Shaw of the University of California, Davis is studying the development of new methods for the synthesis of sulfonimidamides (SIAs). SIAs are organic molecules that do not occur in nature and, as such, are relatively unexplored. They exhibit chirality, i.e. the ability to exist in a “right-” or “left”-handed configuration. This property makes them interesting molecules to study both for their reactivity and for the unique properties that they are expected to impart to new drugs, materials, and other useful applications. The funded research includes investigations into how to make these molecules selectively of one handedness or of largely one enantiomeric configuration using new catalytic methods that will be optimized for efficiency and examined for breadth of application. In addition, this project will examines how this chirality or “handedness”at a sulfur center can influence the formation of new bonds adjacent to the SIA, which will enable the synthesis of new, complex SIAs that have been not been accessed or explored heretofore. These related studies will lay the groundwork for future applications in engineering and medicine that have the potential to open up new vistas for discovery and application. In parallel to the scientific experiments, this project will involve a monthly science café that provides an accessible (and fun!) event where scientists communicate their work to the general public at an off-campus venue. The broader impacts of this work center on enabling the discovery of new molecules to benefit society as well as the public discussion of science from across UC Davis and how it benefits the state, community, and society.The funded research centers on the development of new synthetic methods related to sulfonimidamides (SIAs). This underexplored functional group in organic chemistry provides fertile ground for the discovery from potentially new pharmaceutical lead compounds to new materials and catalysts. This research examines several new catalytic, enantioselective methods for the synthesis of SIAs, including cyclic versions of these molecules that are currently unknown outside of patent literature. These catalytic methods include dynamic kinetic resolution (DKR) using transition metal complexes as well as new phosphorous-based conversion of S=O bonds to S=N bonds. In addition, the impact of sulfur-based chirality on nucleophilic addition reactions that generate new stereogenic centers will be examined. Although previous methods used S-chiral compounds, e.g. sulfinimides, as chiral auxiliaries, this work seeks to make structurally novel SIAs with multiple adjacent carbon stereogenic centers as useful target molecules. Collectively this project aims to take a vertical step in the knowledge of how to make a new functional group in organic chemistry and how that functional group influences the reactivity of adjacent carbon atoms.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.

在化学合成计划的支持下，加利福尼亚大学的Jared T. Shaw教授正在研究开发合成磺酰亚胺酰胺（SIAS）的新方法。 SIA是在自然界中不发生的有机分子，因此是相对出乎意料的。他们暴露了手性，即具有“右”或“左”配置的能力。该特性使他们有趣的分子可以研究其反应性和预期将赋予新药，材料和其他有用应用的独特特性。资助的研究包括对如何使用新的催化方法选择性地使这些分子选择性地进行这些分子或大型对映体构型进行研究，这些方法将得到优化以提高效率并检查了应用的广度。此外，该项目将研究硫磺中心的这种手性或“交接性”如何影响与SIA相邻的新键的形成，这将使未被访问或探索的新的复杂SIA综合。这些相关的研究将为未来在工程和医学中应用的基础，这有可能为发现和应用开放新的远景。与科学实验并行，该项目将涉及一个每月的科学咖啡馆，该咖啡馆提供了一个易于访问的活动（有趣！）活动，在该活动中，科学家在校外场地与公众交流他们的作品。该工作中心对能够发现新分子有益于社会以及对整个UC戴维斯各地的科学讨论及其如何使国家，社区和社会对科学进行公众讨论的更广泛的影响。资助的研究中心与Sulfonimidamides（SIAS）相关的新合成方法（SIAS）。在有机化学中，这个未充满活力的功能组为从潜在的新药铅化合物到新材料和催化剂的发现提供了肥沃的基础。这项研究检查了用于合成SIA的几种新的催化，对映选择性方法，包括这些分子的循环版本，这些分子目前在专利文献之外未知。这些催化方法包括使用过渡金属复合物以及S = O键向S = N键的新基于磷的转化率的动态动力学分辨率（DKR）。此外，将研究基于硫的手性对产生新的立体源性中心的核态性添加反应的影响。尽管以前的方法使用了S-毒物化合物，例如作为手性辅助的亚硫酰亚胺，这项工作旨在使结构新颖的SIA具有多个相邻的碳立体中心作为有用的靶标分子。该项目旨在迈出垂直步骤，了解如何使有机化学的新功能群体以及该功能群体如何影响相邻碳原子的反应性。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子和更广泛的影响审查审查标准来通过评估来通过评估来获得支持的。