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艾莉森·边境教授的研究。 Frontier教授和她的学生正在开发高效的环化反应，这些反应能够创建紧凑的多环分子，这些分子很难使用其他合成策略进行准备。这些化学方法可以快速合成复杂的天然和非天然生物活性分子，尤其是具有特性的小分子在药物发现工作中很有价值。关于教育活动，教育网站（“非伏都教”）的发展仍在继续，该网站被设计为开始在有机化学实验室中独立研究的学生。 Frontier教授用新的资源丰富了该网站，并通过扩大功能来增强访客的体验。该研究计划涉及对新型阳离子反应性的研究以及有效和绿色合成方法的发展。 这些项目着重于多步反应级联反应，这些反应将亲核反应性与阳离子电循环反应合并，并允许执行高度立体控制的环化。这项研究导致人们对氧化还原环化的了解更丰富，这些氧化还原循环是由氢化物转移引发的，与吡啶的耦合和呋喃的oratomatization以及较高阶的电细胞化的执行几乎是未知的反应。还正在评估实现对映选择性电囊化的新策略。拟议的研究旨在探索新的反应性以及有效的，映射和对映选择性方法的发展，这些方法迅速将无环系统转化为桥接，融合或螺旋出的小分子。 合成策略是有效且模块化的，通常以环保的方式进行。 这项研究的小分子靶标具有理想的理化特性，并占据了独特的化学空间。这些特征通常与生物活性相关，并满足既定需求，以提高用于药物发现计划的化合物收集质量。努力还集中在进一步开发的Not Voodoo网站上，该网站每天为数百名有机实验化学家提供服务。