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

生物活性含氮分子的合成与研究新方法

基本信息

批准号：
10796753
负责人：
Qiu Wang
金额：
$ 9.89万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-05 至 2025-08-31
项目状态：
未结题

项目摘要

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.

标题生物活性含氮分子的合成与研究新方法项目概要/摘要小分子探针和药物中普遍存在的氮原子凸显了氮原子的重要性生物医学研究和药物发现中的含氮分子的快速高效合成。结构多样化的含氮骨架至关重要，理解的能力也是如此它们的生物学、药理学以及作为化学探针和候选药物的潜力。新型含氮分子的合成和研究方法对于促进我们对人类疾病的理解和新疗法的发现。药物直接依赖于是否存在能够可靠地构建此类新型药物的具有成本效益的方法分子结构并揭示其生物活性和治疗前景是我们的长期目标。研究的目的是建立一个化学平台，加速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。该项目的目标是开发新的催化选择性烯烃氨基官能化方法，使快速有效地获得结构复杂且功能丰富的新型含氮分子为此，该应用将利用亲电性。基于杂原子-氮键独特且多样的反应性的胺化策略——容易获得但传统上未充分利用的氮前体——设计新的 C-N 键形成反应，这些研究的成功实施将极大地不同于现有方法，但又是其补充。促进各种难以或难以合成的含氮分子的合成和研究使用当前技术无法获得反应工程中的功效和经验教训。选择性将适用于除胺化之外的有用化学过程的发明和开发总的来说，这些新能力在有机合成、医药方面非常有价值和重要。化学、生物医学研究和药物发现，为新型化学的扩展做出了巨大贡献含氮分子的空间和多样性以及新先导化合物和小分子的发现分子探针。