Cascade Cyclizations for Small Molecule Synthesis

小分子合成的级联环化

• 批准号: 1565813
• 负责人: Alison Frontier
• 金额: $ 47万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565813&HistoricalAwards=false
• 关键词: Cascade; Cyclizations; Small; Molecule; Synthesis

The Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Alison Frontier in the Department of Chemistry at the University of Rochester. Professor Frontier and her students are developing highly efficient cyclization reactions which are capable of creating compact polycyclic molecules that are difficult to prepare using other synthetic strategies. These chemical methods enable rapid synthesis of complex natural and non-natural bioactive molecules, especially small molecules with properties demonstrated to be valuable in drug discovery efforts. With respect to educational activities, development continues for an educational website ("Not Voodoo"), which is designed as a resource for students beginning independent research in an organic chemistry laboratory. Professor Frontier enriches the site with new resources, and also enhance the experience of visitors by expanding functionality. The research program involves the study of novel cationic reactivity and the development of efficient and green synthetic methods. The projects focus on multistep reaction cascades that merge nucleophilic reactivity with cationic electrocyclic reactions, and allow the execution of highly stereocontrolled cyclizations. This research is leading to a richer understanding of redox cyclizations which are initiated by hydride shift, cyclizations coupled to pyridine and furan dearomatization, and the execution of higher-order electrocyclizations, which are virtually unknown reactions. New strategies for achieving enantioselective electrocyclization are also being evaluated. The proposed research is directed toward both exploring new reactivity and the development of efficient, diastereo- and enantioselective methods that rapidly transform acyclic systems into bridged, fused, or spirocyclic small molecules. The synthetic strategies are efficient and modular, typically carried out in an environmentally friendly fashion. Small molecule targets of this research have desirable physicochemical properties and occupy unique chemical space; these features often correlate to bioactivity and meet stated needs for improving the quality of compound collections for use in drug discovery programs. Efforts are also focused on further development of the Not Voodoo website, a resource that serves hundreds of organic experimental chemists each day.

NSF 化学部的化学合成计划支持罗切斯特大学化学系 Alison Frontier 教授的研究。 Frontier 教授和她的学生正在开发高效的环化反应，这些反应能够产生使用其他合成策略难以制备的紧凑的多环分子。这些化学方法能够快速合成复杂的天然和非天然生物活性分子，特别是具有被证明在药物发现工作中有价值的特性的小分子。在教育活动方面，教育网站（“Not Voodoo”）的开发仍在继续，该网站旨在为开始在有机化学实验室进行独立研究的学生提供资源。 Frontier 教授用新资源丰富了网站，并通过扩展功能增强了访问者的体验。该研究计划涉及新型阳离子反应性的研究以及高效绿色合成方法的开发。 这些项目侧重于多步反应级联，将亲核反应性与阳离子电环反应相结合，并允许执行高度立体控制的环化。这项研究使我们对由氢化物变换引发的氧化还原环化、与吡啶和呋喃脱芳构化偶联的环化以及高阶电环化的执行有了更丰富的了解，这些反应实际上是未知的。实现对映选择性电环化的新策略也正在评估中。拟议的研究旨在探索新的反应性和开发有效的非对映和对映选择性方法，将无环系统快速转化为桥联、稠合或螺环小分子。 合成策略是高效且模块化的，通常以环保的方式进行。 本研究的小分子靶点具有理想的理化性质并占据独特的化学空间；这些特征通常与生物活性相关，并满足提高药物发现项目中使用的化合物集合质量的既定需求。我们还致力于进一步开发 Not Voodoo 网站，该网站每天为数百名有机实验化学家提供服务。