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

该奖项来自化学合成项目，支持在北卡罗来纳大学威尔明顿分校（UNCW） Thomas Coombs教授的实验室研究和开发构建α -氨基醛酸和相关结构的新方法。在这项工作中使用的氮源可以很容易地操纵氮保护基团与醛结合后。在温和的反应条件下去除这个保护基团的能力有望允许更广泛的功能化醛作为含氮小分子流线型合成的起始材料。通过这些方法生成的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前景。提出的化学在关键步骤中使用有机催化剂和水，有助于这条催化键构建线的发展。北卡罗来纳大学威尔明顿分校（UNCW）在培养STEM领域的学生方面有着悠久的传统。该奖项将允许库姆斯教授为本科生和硕士水平的学生提供动手研究的机会，这些学生有兴趣进行原创性研究，为化学科学的职业生涯做准备。本提案资助的项目将用于教授学生如何从分子角度解决研究问题，并解决实验室中遇到的挑战。本研究旨在开发具有磺胺保护基团的α -氨基醛的对映选择性有机催化合成新方法。这些保护基团可以在非还原条件下去除，允许在起始醛中加入可还原官能团。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-氨基吡咯吲哚啉，以及开发一种对映选择性途径，以烯化α -叠氮醛，用于产生氮杂环的串联反应。提出的研究旨在开发新的对映选择性胺化方法，以简化有机合成。

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.