RUI: Synthesis of Isomeric Carbolines by Tandem Palladium Catalysis

Providence College, Providence RI

Investigators

Abstract

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.