New advances in (4+3)-Cycloadditions

在这个由化学系化学合成计划资助的项目中，密苏里-哥伦比亚大学的迈克尔·哈马塔博士正在开发构建包含原子环的分子的新方法。分子环存在于许多化合物中，它们具有显著的生物活性，对人体健康具有潜在的应用价值。例如用于治疗痛风的秋水仙碱，以及用于治疗疼痛的先导化合物实验性树脂毒素。分子环对新材料的开发也很感兴趣。除了合成这些化合物外，哈马塔博士还在研究这些反应的进展情况。某些分子具有三维结构，这使得它们在镜像上不可叠加，就像右手和左手不能相互叠加一样。哈马塔博士正在开发控制形成哪种镜像产品的方法。由于分子的不同镜像形式可能具有非常不同的生物活性，Harmata博士开发的方法具有广泛的普遍意义。Harmata博士还从事针对年轻化学家和普通公众的活动。他组织了一场名为有机化学日的研讨会，将来自密苏里州和邻近各州的化学家聚集在一起，讨论有机化学前沿。哈马塔博士还在密苏里大学一个名为周六早间科学的项目上发表了演讲。这些外展活动使他不仅可以教授有机化学，还可以解释研究是如何进行的，以及它如何服务于普通公众，有时是服务于六七岁的儿童。最后但并非最不重要的一点是，哈马塔博士赞助了一个暑期项目，让未被充分代表的高中生在他的实验室工作。哈玛塔博士正在研究两个独特的(4+3)-环加成反应。第一种合成方案是不对称催化过程。将这一过程的范围扩大到目前使用的环戊烯氧烯丙基阳离子之外，并了解所观察到的高对映控制的来源，正在进行实验和计算两方面的研究。第二个区域利用在(4+3)-环加成反应中形成的氧化吡啶离子作为亲二烯化合物。这项研究是在最基本的层面上进行的，开发用于简单立体选择以及控制非对映选择性和对映选择性的工具。对于所有提到的反应，研究包括分子间和分子内的前景。最后，正在研究这些反应的独特方面。这些措施包括对产品进行化学修饰，以产生活性物种，如张力烯烃和自由基，从而合成结构更复杂的分子。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Dr. Michael Harmata of the University of Missouri-Columbia is developing new methods for the construction of molecules containing rings of atoms. Molecular rings are found in many compounds that possess significant biological activity and are potentially applicable to human health. Examples include colchicine, used in the treatment of gout, and the experimental resiniferatoxin, a lead compound in the treatment of pain. Molecular rings are also of interest in the development of new materials. In addition to synthesizing these compounds, Dr. Harmata is investigating the how the reactions progress. Certain molecules have a 3-dimentional structure that makes them non-superimposable on their mirror image, just as right and left hands are not superimposable on each other. Dr. Harmata is developing methods to control which mirror image product is formed. Because the different mirror image forms of a molecule can have very different biological activity, the methods Dr. Harmata developed have broad, general significance. Dr. Harmata is also engaged in activities directed towards younger chemists and the general public. He organizes a symposium called Organic Chemistry Day to bring chemists from Missouri and neighboring states together to talk about organic chemistry frontier. Dr. Harmata also speaks at a program at the University of Missouri called Saturday Morning Science. These outreach activities enable him not only to teach organic chemistry, but to explain how research is done and how it serves the general public, sometimes to children as young as six or seven years old. Last but not the least, Dr. Harmata sponsors a summer program for underrepresented high school students to work in his lab. Dr. Harmata is studying two unique (4+3)-cycloaddition reactions. The first synthetic scheme is an asymmetric, catalytic process. Expanding the scope of this process beyond cyclopentenyl oxyallylic cations that are currently being used and understanding the origins of the high enantiocontrol observed are being investigated both experimentally and computationally. The second area makes use of developing oxidopyridinium ions as dienophiles in (4+3)-cycloadditions. This research is being pursued at the most fundamental levels, developing tools for simple stereoselection as well as the control of diastereoselectivity and enantioselectivity. For all of the reactions mentioned, the investigations include both intermolecular and intramolecular prospects. Finally, unique aspects of these reactions are being studied. These include chemical modification of the products to produce reactive species such as strained alkenes and radicals that allow the synthesis of molecules of greater structural complexity.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.