Convenient synthesis of nucleoside-5 '-diphosphates from the corresponding ribonucleoside-5 '-phosphoroimidazole

The reaction of ribonucleoside-5'-phosphoroimidazolide with a tributylammonium orthophosphate in anhydrous dimethylformamide at room temperature provides a general method for the synthesis of nucleoside-5'-diphosphates. The novelty of the approach is to use the triethylammonium salt of 5'-monophosphate nucleoside derivative prior to the imidazolate reaction with imidazole, triphenylphosphine, and 2,2'-dithiodipyridine. Deprotection, followed by displacement of the imidazole moiety using tributylammonium orthophosphate and a catalytic amount of zinc chloride in dimethylformamide gave the desired 5'-diphosphate products. The triethyl ammonium salt of 5'-diphosphate nucleosides was purified by flash chromatography using DEAE ( diethylaminoethyl weak anion exchange resin) Sepharosa fast flow packed in an XK 50/60 column on an Akta FPLC ( Fast Protein Liquid Chromatography). Synthesis procedures are reported for adenosine-5'-diphosphate, uridine-5'-diphosphate, cytidine-5'-diphosphate, and guanosine-5'-diphosphate. Yields for the displacement reactions ranged from 95 to 97%. Thus, this method offers the advantages of shorter reaction time, greater product yield, and a more cost-effective synthetic route.