Synthesis of Some 5′-O-Amino Acid Derivatives of Uridine as Potential Inhibitors of UDP-Glucuronosyltransferase

Article abstract of DOI:10.1007/BF00807604

In an attempt to develop potential inhibitors of UDP-glucuronosyltransferase, some 5′-O-amino acid derivatives of uridine were synthesized. N-protected L-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-threonyl)-2′,3′-O- isopropylideneuridine (1), 5′-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2′,3′-O- isopropylideneuridine (2), 5′-O-(N-tert.butyloxycarbonyl-L-leucyl)-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 of 2 with TFA/ CH₂Cl₂ (6:1) at room temperature for 30 min led to a selective removal of the Boc group without deblocking of the 2′,3′-O-isopropylidene group of uridine. Treatment of 2 with TFA/H₂O (5:1) at room temperature for 1 h, however, released both Boc and 2′,3′-O-isopropylidene groups. The Z group of 1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.