SYNTHESIS OF SOME 5'-O-AMINO ACID-DERIVATIVES OF URIDINE AS POTENTIALINHIBITORS OF UDP-GLUCURONOSYLTRANSFERASE

In an attempt to develop potential inhibitors of UDP-glucuronosyltrans ferase, 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 symme trical anhydrides in presence of 4-dimethylaminopyridine. rt.butyl-L-t hreonyl)-2',3'-O-isopropylideneuridine (1), yl-O-benzyl-L-seryl)-2',3' -O-isopropylideneuridine (2), xycarbonyl-L-leucyl)-2',3'-O-isopropylid eneuridine (3), and 5'-O-(N-tert.butyloxycarbonyl-L-valyl)-2 (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 le d 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 Ih, however, released both Boc and 7/,3'-O- isopropylidene groups. The Z group of 1 was deprotected by catalytic h ydrogenolysis over 10% Pd/C/ammonium formate.