Synthesis Of Derivatives Of 5-ASA For The Treatment Of IBD

The cases of inflammatory bowel diseases (IBD),such as ulcerative colitis and Crohn's disease, which have been popular among Europeans and Americans, are now getting increased in Asian countries such as Japan, Korea and China since the end of the 1990's. The exact etiology of the IBD is not yet clearly understood. Sulfasalazine (SASP) is of proven value in the treatment of IBD and is an agent widely used all over the world. It appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid (5-ASA) in the colon, but its use has be limited by side effects. Great efforts have been done to develop some new kinds of effective 5-ASA derivatives for the treatment of IBD and to reveal the mechanism of the therapeutic action of 5-ASA. However ,so far, these kinds of studies, especially in synthesis, are very few in China. In this paper, we investigated the synthetic route in the conjugating reaction of amino acid and 5-ASA, and four intermediates have been prepared. We characterized their structures. We have synthesized two prodrugs of 5-ASA by the reaction of Glycine methyl ester and Acetaminophen(4-Acetamidophenol), namely, 5-[N-(benzyloxycarbonyl)amino]-2-acetoxysalicylglycine methyl esterand 5 - [N-(benzyloxycarbony l)amino] -2-acetoxy salicylacetaminophen. They are characterized by melting point, elemental analyses, FT-IR, 1H-NMR, 13C-NMR spectra and TLC properties in details. Their structures are given out. By our studying, we have provided a suitable synthesis route for further exploring new compounds in the treatment of IBD.