New Methods for the Synthesis and Study of Bioactive Nitrogen-Containing Molecules

标题 生物活性含氮分子的合成与研究新方法 项目摘要/摘要 氮原子在小分子探针和药物中的普遍存在突显了 生物医学研究和药物发现中的含氮分子。一种高效快速的合成方法 结构多样化的含氮骨架是最重要的，理解 它们的生物学、药理学以及作为化学探针和候选药物的潜力。因此，开发新的 新型含氮分子的合成和研究方法对合成含氮化合物具有重要意义和必要性。 促进我们对人类疾病的理解和新疗法的发现。可广泛使用的 药物的存在直接依赖于成本效益高的方法的存在，这些方法可以可靠地制造出这样的新型药物 并揭示它们的生物活性和治疗前景。我们的长期目标是 研究目的是建立一个化学平台，加快新型小分子化合物的合成和开发 促进对人类疾病的理解和治疗的分子探针和工具。这个 该项目的目标是开发新的催化选择性烯烃氨基功能化方法，使 快速高效地获得结构复杂且官能化程度高的新型含氮分子 以现成的烯烃为起始原料。为此，这一应用程序将利用亲电性 基于杂原子-氮键独特而多样的反应性的胺化策略--很容易获得 然而，传统上未得到充分利用的氮前体-设计新的C-N键形成反应， 与现有方法不同但相辅相成。这些研究的成功实施将极大地 促进合成和研究一系列难以或难以合成的含氮分子 用目前的技术无法访问。在反应工程学中学到的关于疗效和 选择性将适用于胺化以外的有用化学方法的发明和开发 化学反应。总体而言，这些新的能力在有机合成、医学上都是非常有价值和重要的 化学、生物医学研究和药物发现，极大地促进了新化学品的扩展 含氮分子的空间和多样性，以及新的先导化合物和小分子的发现. 分子探测器。

TITLE New Methods for the Synthesis and Study of Bioactive Nitrogen-Containing Molecules PROJECT SUMMARY/ABSTRACT The ubiquitous presence of nitrogen atom in small-molecule probes and drugs highlights the significance of nitrogen-containing molecules in biomedical research and drug discovery. Rapid and efficient synthesis of structurally diverse nitrogen-containing skeletons is of the utmost importance, as is the ability to understand their biology, pharmacology and potential as chemical probes and drug candidates. Thus, developing new methods for the synthesis and study of novel nitrogen-containing molecules is significant and necessary to advance our understanding of human disease and the discovery of new therapies. The broad availability of drugs is directly dependent on the existence of cost-efficient methods that can reliably build such novel molecular structures and uncover their biological activity and therapeutic promise. The long-term goal of our research is to establish a chemical platform that expedite the synthesis and development of novel small- molecule probes and tools toward advancing the understanding and treatment of human disease. The objective of this project is to develop new catalytic selective alkene aminofunctionalization methods that enable rapid and efficient access to structurally complex and richly functionalized novel nitrogen-containing molecules from readily available alkene as starting materials. Toward this, this application will exploit the electrophilic amination strategy based on the unique and diverse reactivity of heteroatom-nitrogen bonds––readily available yet traditionally underutilized nitrogen precursors––to design new C–N bond formation reactions that are different but complementary to existing methods. Successful implementation of these studies will greatly facilitate the synthesis and study of a wide range of nitrogen-containing molecules that are difficult or impossible to access with current technologies. Lessons learned in reaction engineering for efficacy and selectivity will be applicable to the invention and development of useful chemical processes, beyond amination chemistry. Overall, these new abilities are highly valuable and important in organic synthesis, medicinal chemistry, biomedical research, and drug discovery, by greatly contributing to the expansion of novel chemical space and diversity of N-containing molecules as well as the discovery of new lead compounds and small- molecule probes.