Photoelectrocyclizations to Anti-Inflammatory Natural Products

在化学系化学合成(SYN)项目的支持下，犹他大学的这个团队(安德鲁·罗伯茨博士担任Jon Rainier的替补-Pi)将研究小分子抗炎剂的生成和结构细化。雷尼尔研究小组打算用来产生抗炎药的方法将涉及电环化反应。为了实现这些目标，雷尼尔和他的同事们将致力于开发、优化和利用化学，承诺将现成的前体转化为使用环境可持续试剂(即光)的相对复杂的分子系统。除了正在开发的科学，该奖项还承诺帮助培养下一代科学家，他们毕业后将继续在工业和学术界的职业生涯，帮助开发新的化学和重要的药物、材料、农产品和化学品。该奖项中概述的光电环化研究为进入重要抗炎剂支架的创造性途径提供了一条途径。有待探索的核心模型体系是交叉偶联反应生成的双芳基环丁烯酮和单芳基环丁烯酮，将它们转化为相对复杂的多环体系。Rainier小组打算研究底物、取代、反应条件和添加剂对双芳基烯的电环化反应的影响。这些努力将侧重于研究每个反应的效率以及观察到的立体化学结果对每个变量的依赖性。更根本的是，这些研究有望提供对激发态反应性的更好理解，并将测试捕获和操纵通过这种光电环化反应多种多样产生的活性中间体的能力。这一奖项反映了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。

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, this University of Utah team (Dr. Andrew Roberts serves as substitute-PI for Jon Rainier) will study the generation and structural elaboration of small molecule anti-inflammatory agents. The means with which the Rainier team intends to generate the anti-inflammatories will involve electrocyclization reactions. Toward these goals, Rainier and his coworkers will work to develop, optimize, and utilize chemistry that promises to convert readily available precursors into relatively complex molecular systems using environmentally sustainable reagents, namely light. In addition to the science being developed, this award also promises to help to develop the next generation of scientists who will, following their graduation, go on to careers in industry and academia helping to develop new chemistry and important medicines, materials, agricultural products, and chemicals.The photoelectrocyclization studies outlined in this award provide for a creative route into the scaffolds of important anti-inflammatory agents. The core model systems to be explored are bis- and mono-arylcyclobutenones from cross-coupling reactions, converting these into relatively complex polycyclic systems. The Rainier group intends to examine the effect of substrate, substitution, reaction conditions, and additives on the electrocyclization reactions of bis-aryl alkenes. These efforts will be focused on studying the efficiency of each reaction and the dependency of the observed stereochemical outcomes on each of the variables. More fundamentally, these studies are expected to provide an enhanced understanding of excited state reactivity and will test the ability to trap and manipulate reactive intermediates generated through such photoelectrocyclization reaction manifolds.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.