CAREER: New Methods for the Synthesis of Nitrogen-Containing Heterocycles

美国国家科学基金会化学部的化学合成项目用这个职业奖来支持弗吉尼亚大学的Michael Hilinski教授的研究。希林斯基教授正在与研究生和本科生合作，开发新的化学反应，以减少与制备化合物相关的成本、时间和浪费。目标化合物具有在大多数食品和药物管理局批准的药物中发现的结构特征，以及其他类型的化学品，如天然产品，农业化学品和染料。除了提高制造已知结构的能力外，希林斯基实验室还在制造以前无法制造的结构。这使得其他科学家能够探索这些新化合物潜在的、对社会有益的应用。所采用的科学方法侧重于石油副产品与其他廉价化学品反应形成含有至少一个氮原子的环状结构的方法。使用催化剂来促进这些反应，可以对产物进行可预测的控制，并可以合成不同尺寸的环。这些教育活动使学生能够与非科学家就他们的研究和更广泛的科学含义进行交流。希林斯基教授正在为研究生和本科生创建和实施一个新的科学交流研讨会。他还建立了一年一度的化学系开放日活动，他正在为学龄儿童开发一项新的外展活动。由于在药品、天然产品、农用化学品和其他生物活性或其他有用化合物中经常发现含氮杂环，克服其合成中的挑战被认为是具有广泛潜在影响的关键目标。Hilinski教授正在开发饱和或部分饱和氮杂环合成的新方法，该方法在环加成反应中使用亚硝基烯作为单原子组分。目前正在研究几种催化方法来实现这一尚未开发的策略，包括由亚烯转移到烯烃引发的双组分形式环加成，随后是自发的环扩张或重排，以及烯烃、类氮前体和第三组分之间的多组分形式环加成。使用这种策略可以访问不同环尺寸的多类杂环。这种合成方法研究的更广泛的科学影响包括对各种不同化合物类别的合成的广泛潜在适用性。其他更广泛的影响包括通过建立培训讲习班提高学生在科学传播领域的技能，以及通过教育计划使当地社区的人们以一种非专业人员也能接触到的方式接触科学研究。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 this CAREER Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Michael Hilinski of the University of Virginia. Professor Hilinski is working with graduate and undergraduate students to develop new chemical reactions that allow for reductions in the cost, time, and waste associated with preparing chemical compounds. The targeted compounds have structural features that are found in the majority of Food and Drug Administration-approved drugs, as well as in other types of chemicals such as natural products, agricultural chemicals, and dyes. In addition to improving the ability to make known structures, the Hilinski laboratory is making structures that were previously unable to be made. This allows other scientists to explore potentially, societally-beneficial applications of these new compounds. The scientific approach being employed focuses on ways in which petroleum by-products react with other inexpensive chemicals to form ring structures containing at least one nitrogen atom. The use of catalysts to promote these reactions allows for predictable control of the products and for the synthesis of different ring sizes. The educational activities prepare students to communicate with non-scientists about their research and broader scientific implications. Professor Hilinski is creating and implementing a new science communication workshop for graduate and undergraduate students. He is also establishing a yearly Chemistry department open house event, and he is developing a new outreach activity for an audience of school-age children. Owing to the frequency with which nitrogen-containing heterocycles are found in pharmaceuticals, natural products, agrochemicals, and other bioactive or otherwise useful compounds, overcoming challenges in their synthesis is considered a key goal with broad potential impact. Professor Hilinski is developing new methods for saturated or partially saturated nitrogen-heterocycle synthesis that employ nitrenes as one-atom components in cycloaddition reactions. Several catalytic approaches are being pursued to achieve this underexploited strategy, including two-component formal cycloadditions initiated by nitrene transfer to olefins followed by spontaneous ring expansion or rearrangement, and multi-component formal cycloadditions between olefins, nitrenoid precursors, and a third component. Multiple classes of heterocycles of different ring sizes are being accessed using this strategy. The broader scientific impacts of this synthetic methodology research include the wide potential applicability to the synthesis of a variety of different compound classes. Other broader impacts include an enhancement students' skills in the area of science communication via establishment of a training workshop, and, through the education plan, the exposure of people in the local community to scientific research in a way that is accessible to a non-expert.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.