Synthesis and properties of N-substituted saccharin derivatives

Four different routes for the synthesis of saccharin containing peptides were studied. While reactions between saccharin sodium and alpha-halogeno acids were limited to two examples, reactions of sulfobenzoic anhydride (4) or saccharin-N-carboxylate (6) with amino acid esters yielded the ring opened products 5 and 7. Finally, we found, that the reaction between the benzoxathiol derivative 8 and amino acid derivatives represents a versatile route to the peptidic compounds 9 and 11. Hydrolysis and hydrogenolysis were studied, and by combination of the different routes the "saccharin tripeptides" 18 were obtained. Structures and stereochemistry were elucidated by spectroscopic and chromatographic methods. Selected compounds were tested as sweeteners or as inhibitors of elastase, but no exiting results were found.