Synthesis of some 5′-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

In an attempt to develop potential inhibitors ofUDP-glucuronosyltransferase, some 5′-O-amino acid derivatives of uridine were synthesized. N-protectedL-amino acids were coupled at the 5′-O-position of 2′,3′-O-isopropylideneuridine by esterification employing the method of symmetrical anhydrides in presence of 4-dimethylaminopyridine, 5′-O-(N-benzyloxycarbonyl-O-tert.butyl-L-threonl)-2′3′-O-isopropylideneuridine (1), 5′-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2′,3′-O-isopropylideneuridine and (2), 5′-O-(N-tert.butyloxycarbonyl-L-valyl)-2′,3′-O-isopropylideneuridine (3), and 5′-O-(N-tert.butyloxycarbonyl-L-valyl)-2′,3′-O-isopropylideneuridine (4) were obtained in good yield after column chromatography on silica gel. The treatment of2 withTFA/CH2Cl2 (6:1) at room temperature for 30 min led to a selective removal of theBoc group without deblocking of the 2′,3′-O-isopropylidene group of uridine. Treatment of2 withTFA/H2O (5:1) at room temperature for 1 h, however, released bothBoc and 2′,3′-isopropylidene groups. TheZ group of1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.