Diazirines and Diaziridines as Nitrogen Transfer Reagents

在化学部化学合成项目的支持下，佛罗里达州坦帕市H. Lee Moffitt癌症中心的Justin Lopchuk正在研究开发形成碳氮（C-N）键的新方法和试剂。由于含氮化合物在制药科学、农业化学、化学生物学和许多材料/聚合物中都有价值，因此这项工作有望产生广泛的影响。正在开发的方法使用单一试剂从一系列市售原料中产生高价值的C-N键。学生将学习基本的化学原理、催化和与治疗相关的复杂有机分子支架的合成。该资助项目的更广泛影响包括为化学生物学/生物学发现创建一个多样化、富氮化合物筛选库，该库将与教育研讨会和定期虚拟会议一起提供给其他研究人员。后一种努力是为本科生和研究生提供建立网络的机会，并为他们的研究获得更广泛的接触。该项目预计将扩大胺化试剂的范围，并有助于复杂支架的后期胺化和开发更多样化的含n结构，包括含n杂环。更具体地说，Lopchuk小组的重点是使用二氮嘧啶和二氮嘧啶（三元环，两个氮和一个碳）作为新的胺化试剂。在这种方法中，重氮嘧啶将用于与结构不同的起始材料反应，形成重氮嘧啶中间体，这些中间体随后转化为胺（包括15N稳定标记的胺）、肼和含氮杂环，如吡唑、茚唑和吡罗。二氮嘧啶和二氮嘧啶的使用避免了其他亲电试剂和自由基胺化试剂的许多缺点，包括它们的不稳定性，它们缺乏官能团耐受性，和/或在C-N键形成下游加工它们所需的苛刻条件。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Justin Lopchuk of H. Lee Moffitt Cancer Cente in Tampa, Florida is studying the development of new methods and reagents to form carbon-nitrogen (C-N) bonds. This work is expected to have broad impact because nitrogen-containing compounds are valuable in pharmaceutical science, agricultural chemistry, chemical biology and in many materials/polymers. The methods being developed use a single reagent to create high value C–N bonds from a range of commercially available starting materials. Students doing this work will be trained in fundamental chemical principles, catalysis and the synthesis of complex organic molecular scaffolds of relevance to therapeutics. The broader impacts of the funded project include the creation of a diverse, nitrogen-rich compound screening library for chemical biology/biological discovery that will be made available to other researchers along with educational workshops and recurring virtual conferences. These latter efforts are being developed to provide opportunities for undergraduate and graduate students to network and to receive wider exposure for their research.This project is expected to expand the scope of amination reagents and contribute to both the late-stage amination of complex scaffolds and to developing a more diverse set of N-containing architectures, including N–containing heterocycles. More specifically, the Lopchuk group is focused on the use of diazirines and diaziridines (three-membered rings with two nitrogens and one carbon) as novel amination reagents. In this approach diazirines will be used in reactions with structurally diverse starting materials to form diaziridine intermediates that are subsequently converted into amines (including 15N stable labeled amines), hydrazines, and nitrogen-containing heterocycles such as pyrazoles, indazoles, and pyrroles. The use of diazirines and diaziridines avoids many of the drawbacks that have been seen with other electrophilic and radical amination reagents including their instability, their lack of functional group tolerance, and/or the harsh conditions needed for processing them downstream of C–N bond formation.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.