Part I. Design and synthesis of ureidopeptides as protease inhibitors. Part II. Novel synthesis of a fluorescent coumaryl amino acid

Utilizing a one-pot oxidative Hofmann rearrangement, a class of pseudopeptides which we term ureidopeptides has been synthesized. The formation of these ureidopeptides occurs from the oxidative Hofmann rearrangement of a carboxamide to its corresponding isocyanate using bistrifluoroacetoxyiodobenzene, followed by reaction with an amine to form the urea. By incorporating the urea functionality into a peptide backbone, peptide sequences can be converted to protease inhibitors. If the substrate cleavage sequence of a protease is known, the hydrolytically stable urea can replace the scissile amide bond. This strategy has been applied to the inhibition of both HIV-1 protease and SARS protease in this work. The Lipton research group has undertaken the synthesis of a family of marine natural products known as the callipeltins. These cyclic depsipeptides have been shown to possess a wide variety of biological activities, thus are synthetic targets of interest. The two main aims of our synthesis is determining the absolute stereochemical configuration of the molecules and their modes of action, both of which are yet unknown. To accomplish the mode of action studies for these compounds, fluorescence will be monitored via a fluorescent tag for the molecule. To this end, it has been chosen to replace the β-methoxytyrosine, common to the callipeltins and several other depsipeptide natural products with a fluorescent amino acid. A coumaryl amino acid will be synthesized via a novel procedure to carry out this procedure