With this Award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Carl Lovely, University of Texas-Arlington to work with undergraduate and graduate students to develop new methods for the construction of complex organic structures, such as those that might used in chemical biology or medicinal chemistry studies. In the present research, new methods and strategies are being invented to allow the assembly of complex molecular frameworks through tandem reactions in order to increase synthetic efficiency. Tandem reactions involve the sequencing of two or more chemical reactions such that the first reaction sets up the second and so on. Such strategies have potential to increase efficiency by reducing the number of synthetic steps required in a process, thereby reducing the use of organic solvent and the number of purification steps required. Plans are outlined to apply the new methodology to the synthesis of two natural products originally isolated from marine invertebrates. These natural products are of interest due to their unusual bicyclic architectures. These challenging target structures have both inspired the methodology and are seen to have potential for chemical biology studies Additional benefits which accrue from this project include the recruitment and participation of under-represented high school, undergraduate and graduate students. In particular, one project has been specifically designed with the participation of high school students in mind. In this latter context, students have the opportunity to do research in organic synthesis that otherwise would not be available to them.
Professor Lovely and his students develop new methods for the construction of novel heterocyclic molecules using chemistry known as oxidative dearomatizing spiro-cyclization. In this research, the dearomatization process is linked with a second chemical transformation leading to tandem reaction processes. Such sequential transformations permit the experimentalist to achieve a rapid increase in molecular complexity in one synthetic operation. Such tactics provide advantages in terms of synthetic efficiency and reduction in the cost of resources. Specifically, this work examines the oxidative cyclization of guanidines, thioureas, and ureas both in terms of the reaction scope but also to provide a detailed mechanistic understanding of the process. Two natural products have been identified to test the limits of the proposed chemistry by taking advantage of the efficiency gains. Both targets are secondary metabolites isolated from marine invertebrates which have yet to succumb to total synthesis efforts and may serve as lead compounds in medicinal chemistry investigations. The tandem reactions being investigated in the course of this work provide rapid access to the core structural features of these molecules. Broader impacts of this work include the recruitment and training of the next generation of scientists, including members of groups that are under-represented in the chemical sciences.
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.
