RUI: Asymmetric Synthesis of Atropisomeric beta-Carbolines

通过这一奖项，美国国家科学基金会化学部的化学合成计划支持Seann Mulcahy教授的研究。马尔卡西教授是普罗维登斯学院化学和生物化学系的教员，普罗维登斯学院是罗德岛州普罗维登斯的一所主要是本科生的文科学院。马尔卡希教授与一组本科生一起，正在开发新的化学工具，用于制造被称为阿托品的有机分子。这些分子是独一无二的，因为它们不能完全围绕它们的一个碳-碳单键旋转。这一限制将阿托菲异构体锁定在两个截然不同的螺旋桨状形态中，这两个形态是彼此不同的镜像。在化学合成领域，制备这些形式中的一种或另一种形式是一个挑战，但获得这些不同的分子对于制药和材料应用非常重要。马尔卡希教授正在研究使用过渡金属催化剂将关键成分缝合在一起，有选择地制造新的阿托品的方法。一个不同的本科生团队正在接受培训，他们致力于优化这种催化反应，并研究这些分子的性质。普罗维登斯学院的计算研究以及与圣地亚哥州立大学杰弗里·古斯塔夫森教授的合作都被用来帮助指导这些调查。马尔卡西教授还在大普罗维登斯地区为未被充分代表的高中生组织化学合成研讨会，为对研究感兴趣的高三学生创建暑期沉浸计划，并为大学生开发新的资源，以应对失败并在STEM中更具弹性。过渡金属催化是构建不对称碳立体中心的有效方法；然而，使用过渡金属催化安装其他类型的手性还不太发达。普罗维登斯学院的Mulcahy小组正在开发催化不对称方法来合成阿托品杂环1-芳基-β-碳氢化合物。本项目的目标是开发一种阳离子Rh(I)催化的[2+2+2]环加成策略，利用催化剂优化、底物工程和计算方法相结合的方法选择性地形成两个镜像异构体之一。手性双齿膦配体的影响和试剂的取代模式作为阿托品选择性的关键决定因素正在被探索。此外，正在进行计算和物理化学研究，以确定阿托品异构体的绝对构型和消旋速率。这些活动也是对各类合成化学本科生进行教育和培训的平台，也是招募和留住人数不足群体的学生的平台。创建新的视频资源来帮助学生处理他们在研究环境中可能遇到的挑战，正在作为一种新的资源来开发，以进一步支持STEM领域的纳入和扩展。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。

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Seann Mulcahy. Professor Mulcahy is a faculty member in the Department of Chemistry and Biochemistry at Providence College, a primarily undergraduate liberal arts college in Providence, Rhode Island. Together with a team of undergraduate students, Professor Mulcahy is developing new chemical tools for making organic molecules known as atropisomers. These molecules are unique because they cannot fully rotate around one of their carbon-carbon single bonds. This limitation locks the atropisomers in two distinct propeller-like forms that are non-identical mirror images of one another. Preparing one or the other of these forms is a challenge in the field of chemical synthesis but access to these distinct molecules is important for pharmaceutical and material applications. Professor Mulcahy is researching ways to selectively make new atropisomers using a transition metal catalyst to stitch together the key components. A diverse team of undergraduate students are receiving training by working to optimize this catalytic reaction and study the properties of these molecules. Computational studies both at Providence College and in collaboration with Professor Jeffrey Gustafson at San Diego State University are being used to help guide these investigations. Professor Mulcahy is also organizing workshops in chemical synthesis for underrepresented high school students in the greater Providence region, creating a summer immersion program for high school juniors interested in research, and developing new resources for college students to cope with failure and be more resilient in STEM.Transition metal catalysis is a powerful method for the construction of asymmetric carbon stereocenters; however, the use of transition metal catalysis to install other types of chirality is less well-developed. The Mulcahy group at Providence College is developing catalytic asymmetric methods to synthesize atropisomeric heterocyclic 1-aryl-beta-carbolines. The goal of this project is to develop a cationic rhodium(I)-catalyzed [2+2+2] cycloaddition strategy for the selective formation of one of the two mirror-image atropisomers using a combination of catalyst optimization, substrate engineering, and computational methods. The effects of chiral bidentate phosphine ligands and the substitution patterns of the reagents are being explored as key determinants of atroposelectivity. In addition, computational and physicochemical studies are being performed to determine the absolute configuration and establish the rates of racemization of the atropisomeric beta-carbolines. These activities are also serving as a platform for the education and training of a diverse set of undergraduate students in synthetic chemistry, as well as the recruitment and retention of students from underrepresented groups. The creation of new video resources to help students manage challenges that they might encounter in a research setting are being developed as a new resource to further support inclusion and expansion in STEM fields.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.