Design and syntheses of colon-specific pro-antedrugs for oral treatment of ulcerative colitis

Abstract

Both hydrophilic steroid derivatives, methyl 20-α-glucopyranosyloxy prednisolonates(9 and 10) and methyl prednisolonate 20-sodium sulfates(11 and 12) were synthesised from prednisolone via methyl 20 (S/R)-dihydroprednisolonates(1 and 2) based on a new colon-specific drug-delivery system. Optimal conditions for the syntheses of each isomers (1) and (2) were found by the extensive studies on the reaction rates from prednisolone under various concentrations of cupric acetate in dry methanol. Their configurations at C20 in (1) and (2) were determined by their formation mechanism and ¹HNMR spectroscopic studies of the corresponding acetates (3) and (4).