Diazirines and Diaziridines as Nitrogen Transfer Reagents

在化学系化学合成项目的支持下，H。位于佛罗里达坦帕的李·莫菲特癌症中心正在研究开发形成碳-氮（C-N）键的新方法和试剂。这项工作预计将产生广泛的影响，因为含氮化合物在制药科学，农业化学，化学生物学和许多材料/聚合物中有价值。正在开发的方法使用单一试剂从一系列市售的起始材料中产生高价值的C-N键。从事这项工作的学生将接受基本化学原理、催化和与治疗相关的复杂有机分子支架合成方面的培训。该资助项目的更广泛影响包括创建一个多样化的富氮化合物筛选库，用于化学生物学/生物学发现，该库将与教育研讨会和定期虚拟会议一起沿着提供给其他研究人员。这些后者的努力正在开发，为本科生和研究生提供机会，以网络和接受更广泛的曝光为他们的research.This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一套更多样化的含N结构，包括含N杂环。更具体地说，Lopchuk小组专注于使用二氮杂环丙烷和二氮杂环丙烷（具有两个氮和一个碳的三元环）作为新型胺化试剂。在该方法中，二氮杂环丙烷将用于与结构上不同的起始材料反应以形成二氮杂环丙烷中间体，其随后转化为胺（包括15 N稳定标记的胺）、肼和含氮杂环如吡唑、吲唑和吡咯。二氮杂环丙烷和二氮杂环丙烷的使用避免了其它亲电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-反应器下游处理它们所需的苛刻条件。该奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的支持。影响审查标准。

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.