This project will continue work on developing a general and versatile methodology for the synthesis of novel organophosphorus compounds using solid-phase phosphitylating reagents. Most solution- and solid-phase strategies for the synthesis of organophosphorus compounds have been hampered by the absence of regioselectivity, low overall yields, production of multiple-substituted derivatives, the need for protection and deprotection, and extensive purification of intermediates and/or final products from the reagents. In this project, several novel solid-phase reagents that can be utilized in reactions with unprotected nucleosides and carbohydrates will be studied for the regioselective synthesis of modified organophosphorus compounds. These reagents will be used for the synthesis of nucleotides including imidophosphates, methylenephosphates, tetraphosphates, unsymmetrical phosphodiesters, phosphoramidates, phosphorodithioates, and phosphoroamidothioates.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Keykavous Parang of the Department of Biomedical and Pharmaceutical Sciences at the University of Rhode Island. Professor Parang's research efforts revolve around the design of several solid-phase reagents for the synthesis of a variety of organophosphorus compounds. These organophosphorus compounds could be valuable resources for the discovery of enzyme inhibitors of nucleic acid synthesis. Successful development of the strategy will advance the scientific knowledge in the area of solid-phase organic synthesis. Finally, transfer of technical knowledge and expertise to the chemical industry will have a potential impact on economical development.
