Design, Synthesis, and Testing of a Molecular Truck for Colonic Delivery of 5-Aminosalicylic Acid

A molecular scaffold bearing eight terminal alkyne groups was synthesized from sucrose. Eight copies of an azide-terminated, azo-linked precursor to 5-aminosalicylic acid were attached to the scaffold via copper(I)-catalyzed azide–alkyne cycloaddition. The resulting compound was evaluated in a DSS model of colitis in BALB/c mice against sulfasalazine as a control. Two independent studies verified that the novel pro-drug, administered in a dose calculated to result in an equimolar 5-ASA yield, outperformed sulfasalazine in terms of protection from mucosal inflammation and T cell activation. A separate study established that 5-ASA appeared in feces produced 24–48 h following administration of the pro-drug. Thus, a new, orally administered pro-drug form of 5-aminosalicylic acid has been developed and successfully demonstrated

Synthesis of ureidopeptides using pentafluorophenyl carbamates from Nα-Fmoc-peptide acids

910-919Highly active and shelf stable pentafluoro phenol derived Fmoc-peptidyl carbamates have been synthesized from corresponding Fmoc-peptidyl isocyanates. The utility of pentafluorophenyl carbamate intermediates has been demonstrated by the synthesis of tri, penta and hexapeptidyl ureas which are obtained in good yields. All the synthesised compounds have been characterized by ¹H NMR, ¹³C NMR and mass spectroscopy. The coupling reaction using pentafluorophenyl carbamates to insert urea bond between α amino acids is fast, clean and high yielding