The synthesis of imidodiphosphate analogues of natural nucleoside 5'-diphosphates including adenosine 5'-imidodiphosphate (4a), guanosine 5'-imidodiphosphate (4b), 2'-deoxyadenosine 5'-imidodiphosphate (4c), and 2'-deoxy-guanosine 5'-imidodiphosphate (4d) has been accomplished for the first time. These compounds are the products of the reaction between nucleosides and trichloro [(dichlorophosphoryl)imido] phosphorane in trimethyl phosphate. Some of the major by-products of the reaction including 5'-deoxy-5'-chloro nucleosides are discussed. Compounds 4b, 4c, and 4d are potent inhibitors of ecto-5'-nucleotidase whereas compound 4a also active but less potent inhibitor. Compound 4b is the most potent inhibitor of phosphoribosyl pyrophosphate (PPRP) synthetase which follows by 4c, 4d and 4a. All of these compounds were more potent inhibitor of PPRP-synthetase than ADP or GDP. Ribavirin imidodiphosphate (4e) was also synthesized and tested for its inhibitory effect on ecto-5'-nucleotidase, PPRP-synthetase as well as IMP dehydrogenase. Compound 4e is the most potent inhibitor of IMP dehyrogenase but was a weak inhibitor of the other two enzymes. compound 4a, 4b, 4c and 4d are weak inhibitors of IMP dehydrogenase.