Principal Investigator/Program Director (Last, First, Middle): Ahmd-Schofield, Ruquia, Bibi Project Summary/Abstract Many heterocyclic compounds have important physiological properties making them vital targets for organic synthesis. Hence, there is great interest in the development of new synthetic methodology to the construction of heterocycles. The overall goal of the proposed research is to conduct model studies to investigate a methodology for the construction of spirocyclic amines. The methodology is based upon the photodecomposition of cyclic derivatives of Barton PTOC [((1H)-pyridine-2-thione)- oxycarbonyl] esters in the presence of nucleophilic amines. The attractive feature of the strategy lies in its potential for short, versatile, and efficient syntheses. Depending upon the structural nature of the nucleophilic amine, an array of products is possible. Some of the photoproducts have structural features that are found in some interesting and biologically active compounds. Successful outcome of these model studies will set the foundation for utilizing this methodology towards the synthesis of numerous structural derivatives, many of which are expected to show pharmaceutical potential. The potential of this methodology for chiral induction will also be investigated. The outcome of stereochemical studies is expected to set the foundation for an entirely new and exciting research direction (not included in this proposal).
The specific aims are: (a) to synthesize several cyclic derivatives of Barton PTOC ester, (b) to investigate the photodecomposition reactions of the cyclic ester derivatives with nucleophilic amines, (c) to study the scope and limitation of substituent effects, and the regio- and stereochemical outcome of these reactions, and (d) to demonstrate the synthetic versatility of this type of reaction. Future direction includes the construction of potential targets with structural features that have been shown to possess interesting and potent biological activity. Principal Investigator/Program Director (Last, First, Middle): Ahmd-Schofield, Ruquia, Bibi . Project Narrative: Relevance of this Project to Public Health The overall goal of the propose research is to investigate a simple and versatile methodology for the construction of spirocyclic amines. Some of the expected products of the model studies have structural features that are found in some interesting and biologically active compounds. Results from this study will lay the foundation for future synthetic work targeting selected biologically significant compounds. ? ? ?
