Cascade Cyclizations for Small Molecule Synthesis

NSF化学部的化学合成计划支持罗切斯特大学化学系艾莉森·边疆教授的研究。 Frontier教授和她的学生正在开发高效的环化反应，能够创造出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，特别是具有在药物发现工作中被证明有价值的性质的小分子。在教育活动方面，继续开发一个教育网站（“Not Voodoo”），该网站是为在有机化学实验室开始独立研究的学生设计的一个资源。Frontier教授用新的资源丰富了网站，并通过扩展功能来增强访问者的体验。该研究计划包括研究新型阳离子反应性和开发高效和绿色合成方法。 该项目的重点是多步反应级联，合并亲核反应与阳离子电环化反应，并允许执行高度立体控制的环化。这项研究导致更丰富的理解氧化还原环化，这是由氢化物移位，环化耦合到吡啶和呋喃脱芳构化，和执行高阶电环化，这是几乎未知的反应。实现对映选择性电环化的新策略也正在评估中。拟议的研究是针对探索新的反应性和开发有效的，非对映体和对映体选择性的方法，快速转换成桥，融合，或螺环小分子的非环状系统。 合成策略是有效的和模块化的，通常以环境友好的方式进行。 本研究的小分子靶点具有理想的物理化学性质，并占据独特的化学空间;这些特征通常与生物活性相关，并满足用于药物发现计划的化合物集合的质量改善的需求。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。

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.