RUI: Synthesis of Isomeric Carbolines by Tandem Palladium Catalysis

NSF化学部的化学合成计划支持普罗维登斯学院化学和生物化学系的Seann Mulcahy教授的研究。Mulcahy教授和他的本科生正在开发一种新的方法来合成一类称为异构咔啉的有机化合物。已知这些分子具有吸引人的生物学特性，其范围从神经化学作用到抗菌和抗癌活性。该项目的一个主要目标是使用含有钯元素的化合物作为催化剂，将这些分子从更简单的前体缝合在一个容器中。 这种有效的化学方法将减少合成咔啉所需的时间、能量和资源。该项目还作为普罗维登斯学院本科生的培训工具，包括来自弱势背景的学生。该项目的广度超出了研究实验室，并正在纳入本科课程，夏桥计划，并在普罗维登斯公立学校的推广活动。所有参与这项工作的学生都获得了解决问题和批判性思维能力，这是在各级化学成功所必需的。该项目涉及开发用于合成异构体α，β，γ和δ-咔啉杂环的催化，一锅法程序，这些杂环具有重要的生物化学功能，包括神经药理学活性。这项研究的特定目标有可能作为研究大脑疾病的分子探针。在这项工作中的总体策略是使用一个单一的钯前体，将催化两个机械独特的转换。第一个目标是完成具有附加环的β-咔啉的合成。通过在同一烧瓶中进行串联Sonogashira/[2+2+2]环化，使用“多任务”钯催化剂以原子经济的方式产生这些分子。第二个目标是为更富电子的α-咔啉异构体设计类似的策略。最终的科学目标是合成前体炔腈和官能化碘苯胺分子，从而产生γ-和δ-异构体。基板范围，催化效率，和配体/溶剂的影响进行了优化，为每个异构体类。在这项工作中，同样重要的是培养本科生成为更好的科学家。通过参与原创性研究，本科生探索化学合成和催化的新领域。该项目还寻求招募代表性不足的群体学习化学，无论是通过“夏桥”的研究经验，为新生或催化剂化学外展计划在普罗维登斯公立学校。

The Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Seann Mulcahy in the Department of Chemistry and Biochemistry at Providence College. Professor Mulcahy and his undergraduate students are developing a new methodology for the synthesis of a class of organic compounds called isomeric carbolines. These molecules are known to have attractive biological properties, which range from neurochemical effects to antibacterial and anticancer activity. One major goal of this project is to use compounds containing the element, palladium, as a catalyst that will stitch together these molecules in a single vessel from simpler precursors. Such an efficient chemical process would reduce the time, energy, and resources needed for the synthesis of carbolines. The project further is serving as a training tool for undergraduate students at Providence College, including those students from disadvantaged backgrounds. The project's breadth reaches beyond the research laboratory and is being incorporated into the undergraduate curriculum, a summer bridge program, and outreach activities in Providence public schools. All of the students involved in this work are gaining problem solving and critical thinking skills that are needed for success in chemistry at all levels. This project involves the development of catalytic, one-pot procedures for the synthesis of isomeric alpha, beta, gamma and delta-carboline heterocycles that have important biochemical function including neuropharmacological activity. Specific targets of this research have potential as molecular probes for studying diseases of the brain. The overarching strategy in this work is the use of a single palladium precursor that will catalyze two mechanistically unique transformations. The first objective is to complete the synthesis of beta-carbolines which have an additional ring attached. By performing a tandem Sonogashira/[2+2+2] cyclization in the same flask, these molecules are created in an atom-economical way using a "multitasking" palladium catalyst. The second objective is to devise similar strategies for the more electron-rich alpha-carboline isomers. The final scientific objective is to synthesize precursor alkynylnitrile and functionalized iodoaniline molecules leading to the gamma- and delta-isomers. The substrate scope, catalytic efficiency, and ligand/solvent effects are optimized for each isomeric class. Equally important in this work is the training of undergraduate students to become better scientists. Through their involvement in original research, undergraduates explore new areas of chemical synthesis and catalysis. The project also seeks to recruit underrepresented groups to study chemistry, both through a "summer bridge" research experience for incoming students or the Catalysts for Chemistry outreach program in Providence public schools.