Synthesis of 5′-O-Oligopeptide Derivatives of Uridine as Inhibitors of UDP-glucuronosyltransferase

In order to design potential inhibitors of UDP-glucuronosyltransferase, the synthesis of some 5′-O-oligopeptide derivatives of uridine is presented. 5′-O-(N-tert.Butyloxycarbonyl-O-benzyl-L-seryl-L-valyl)-2′,3′-O-isopropylideneuridine (1) was synthesized by the DCC/HOBt method from N-tert.butyloxycarbonyl-O-benzyl-L-serine and 5′-O-L-valyl-2′,3′-O-isopropylideneuridine in 95% yield. In a similar way, 5′-O-(N-tert.butyloxycarbonyl-L-valyl-O-benzyl-L-seryl)-2′,3′-O-isopropylideneuridine (2) was obtained from N-tert.butyloxycarbonyl-L-valine and 5′-O-(O-benzyl-L-seryl)-2′,3′-O-isopropylideneuridine in 93% yield. Treatment of 1 and 2 with HCl/EtOAc at room temperature for 30 min led to removal of both Boc and 2′,3′-O-isopropylidene groups. 5′-O-(O-Benzyl-L-seryl-L-valyl)-uridine (3) and 5′-O-(L-valyl-O-benzyl-L-seryl)-uridine (4) were obtained in 94% and 91% yields, respectively.