RUI: Catalytic Methods for the Enantioselective Synthesis of Enolizable Alpha-Amino and Alpha-Azido Aldehydes and Novel Applications Thereof

RUI：对映选择性合成烯醇化α-氨基和α-叠氮醛的催化方法及其新应用

• 批准号: 1464958
• 负责人: Thomas Coombs
• 金额: $ 24万
• 依托单位: University of North Carolina at Wilmington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464958&HistoricalAwards=false
• 关键词: RUI; Catalytic; Methods; Enantioselective; Synthesis

This award from the Chemical Synthesis program supports the research and development of new methods for constructing alpha-amino aldehydes and related structures in the laboratory of Professor Thomas Coombs at the University of North Carolina Wilmington (UNCW). The nitrogen sources used in this work allow easy manipulation of the nitrogen protecting group following their union with aldehydes. The ability to remove this protecting group using mild reaction conditions is expected to permit a broader range of functionalized aldehydes to serve as starting materials in streamlined syntheses of nitrogen-containing small molecules. The alpha-amino aldehydes generated via these methods can be transformed into a range of nitrogen-containing compounds with potential applications in medicinal chemistry and chemical biology. The proposed chemistry uses organocatalysts and water in the key steps, contributing to the development of this line of catalytic bond construction. The University of North Carolina Wilmington (UNCW) has a strong tradition of training students in STEM fields. This award will allow Professor Coombs to extend hands-on research opportunities to both undergraduate and M.S.-level students interested in conducting original research in preparation for careers in chemical science. The projects funded in this proposal will be used to teach students how to approach research questions from a molecular perspective and to troubleshoot challenges encountered in the laboratory.The proposed research is aimed at developing new methods for the enantioselective organocatalytic synthesis of enolizable alpha-amino aldehydes bearing sulfonamide protecting groups. These protecting groups may be removed under non-reductive conditions, permitting the incorporation of reducible functional groups in the starting aldehydes. Extending these methods to use tryptamines as reaction substrates for the synthesis of 3-amino-pyrroloindolines via a similar mechanism will also be investigated, as will the development of an enantioselective route to enolizable alpha-azido aldehydes for use in tandem reactions generating nitrogen heterocycles. The proposed research seeks to develop new enantioselective amination methods for streamlining organic synthesis.

化学合成计划的这一奖项支持威尔明顿大学（UNCW）北卡罗来纳州托马斯库姆斯教授实验室构建α-氨基醛和相关结构的新方法的研究和开发。 在这项工作中使用的氮源允许在氮保护基团与醛结合之后容易地操作氮保护基团。 使用温和的反应条件除去该保护基的能力预期允许更宽范围的官能化醛用作含氮小分子的流线型合成中的起始材料。通过这些方法产生的α-氨基醛可以转化为一系列含氮化合物，在药物化学和化学生物学中具有潜在的应用。所提出的化学方法在关键步骤中使用有机催化剂和水，有助于这一系列催化键结构的发展。 北卡罗来纳州威尔明顿大学（UNCW）有着培养学生STEM领域的悠久传统。 该奖项将允许教授库姆斯扩大动手研究的机会，本科和硕士-有兴趣进行原创性研究的学生，为化学科学的职业生涯做准备。 本项目资助的项目将用于教授学生如何从分子的角度处理研究问题，并解决实验室中遇到的挑战。拟议的研究旨在开发对映选择性有机催化合成具有磺酰胺保护基团的烯醇化α-氨基醛的新方法。 这些保护基可以在非还原性条件下除去，允许在起始醛中引入可还原的官能团。 将这些方法扩展到使用色胺作为反应底物，通过类似的机制合成3-氨基-吡咯并吲哚啉也将进行研究，因为将开发的对映选择性路线烯醇化的α-叠氮醛用于串联反应产生氮杂环。 该研究旨在开发新的对映选择性胺化方法，以简化有机合成。