(4+3) Cycloadditions of Oxidopyridinium and Oxidopyrylium Ions

在化学系化学合成（SYN）项目的支持下，密苏里-哥伦比亚大学的Michael Harmata教授正在研究一系列产生七元碳原子环的化学反应。正在研究的转化涉及所谓的[4+3]-环加成，其中在含有氮原子（氧化吡啶离子）或氧原子（氧化吡啶离子）的活性物质中跨越三个原子的结构域以有组织的方式加入到四个原子跨越的组分（二烯）中。这项研究很重要，因为它将促进在生物活性分子中常见的七元环环亚结构的产生，包括天然产物和药物制剂。此外，有关分子反应性和键合等问题的基本新见解可能会从这些研究中出现。更广泛的影响将包括一个高中外展项目，包括来自传统上在科学、技术、工程和数学（STEM）领域代表性不足的群体的学生，并通过基于实验室的暑期实习提供先进的化学经验。Harmata教授还将组织一个名为“周六早间科学”的活动，届时来自密苏里-哥伦比亚大学各地的教师将向公众展示他们的研究成果，以激发和培养各年龄段社区成员对科学的兴趣。资助的研究重点是对标题物种的[4+3]-环加成化学的重大进一步发展，重点是确定可行的策略来实现高水平的区域和立体控制。此外，将复杂的双环加合物转化为最终目标的裁剪过程，包括生物活性生物碱，也同样在研究中。本研究的一个主要目的是研究含硫或硅取代基的共轭二烯环加成的动力学和热力学效应，以达到区域控制的目的。在其他工作中，将探索环加合物桥头堡位置的功能化，以进一步扩大所追求的化学的效用。最后，研究了环加合物转化为环庚[b]-吡咯和环庚[b]吲哚的反应。这种杂环被认为是特权结构，因为它们出现在许多生物和制药兴趣的生物碱中。这些研究建立在PI实验室大量工作的基础上，通过[4+3]-环加成化学来确定复杂环结构构建的潜力，因此，有望更完整地定义合成有机化学的这个有趣的维度。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 the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Michael Harmata of the University of Missouri-Columbia is studying a family of chemical reactions that generate seven-membered rings of carbon atoms. The transformations being investigated involve so-called [4+3]-cycloadditions, wherein a domain spanning three atoms within a reactive species containing either a nitrogen atom (oxidopyridinium ion) or an oxygen atom (oxidopyrylium ion), adds in an organized fashion to a four atom-spanning component (a diene). This research is important because it will facilitate the generation of seven-membered ring cyclic substructures that occur commonly in biologically active molecules, including natural products and pharmaceutical agents. In addition, fundamental new insights concerning issues such as molecular reactivity and bonding are likely to emerge from these studies. The broader impacts will include a high school outreach program that includes students from groups traditionally underrepresented in science, technology, engineering, and mathematics (STEM) fields and provides advanced chemistry experiences through laboratory-based summer internships. Professor Harmata will also organize an event called “Saturday Morning Science,” at which faculty from across the University of Missouri-Columbia will present their research to the general public in a manner that will excite and cultivate an interest in science among members of the community of all ages.The funded research focuses on significant further development of the [4+3]-cycloaddition chemistry of the title species with an emphasis on the identification of viable strategies to effect high levels of regio- and stereocontrol. In addition, tailoring processes to convert the complex bicyclic cycloadducts into targets of ultimate interest, including bioactive alkaloids, are likewise under investigation. In a major aim of the research, kinetic and thermodynamic effects in the cycloadditions of conjugated dienes bearing sulfur or silicon substituents will be studied for the purpose of achieving regiocontrol. In other work, functionalization of the bridgehead positions of the cycloadducts will be explored to further extend the utility of the chemistry being pursued. Finally, the conversion of the cycloadducts to cyclohepta[b]-pyrroles and cyclohepta[b]indoles will be developed. Such heterocycles are considered privileged structures as they appear in many alkaloids of biological and pharmaceutical interest. These studies build upon a substantial body of work in the PI's laboratory to define the potential for complex cyclic ring structure construction through [4+3]-cycloaddition chemistry and, as such, are expected to define more completely this interesting dimension of synthetic organic chemistry.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.