A SIMPLE MULTI-GRAM SYNTHESIS OF 5'-HYDROGENPHOSPHONATES AND 5'-PHOSPHOROFLUORIDATES OF SUGAR MODIFIED NUCLEOSIDES

Treatment of 3'-fluoro-3'-deoxythymidine (FLT), 3'-azido-3'-deosxthymi dine (AZT) and 2',3'-dideoxyadenosine (ddA) with tris(1,1,1,3,3,3-hexa fluoro-2-propyl)phos or phosphorous acid and N,N'-dicyclohexylcarbodii mide produced the corresponding nucleoside 5'-hydrogenphosphonates. Re action of FLT, AZT and 3'-deorrythymidine (ddT) with fluorophosphoric acid and 2,4,6-triisopropylbenzenesulfonyl chloride lead to the corres ponding nucleoside 5'-phosphorofluoridates also on a multi-gram scale. All the compounds were isolated in high pure state by chromatographic technique.