The synthesis of an acyclic nucleotide analogue, (E)-9-(3-phosphonylmethoxypropen-1-yl)adenine

(E)-9-(3-Hydroxypropen-1-yl)adenine was obtained by alkylation of adenine with 1,2-di-O-mesyl-3-O-tritylglycerol followed by elimination of mesyl group and detritylation. Cis/trans selectivity of the reaction was investigated. The resulting hydroxypropenyladenine was alkylated by ethyl iodomethylphosphonate in the presence of NaH, and treated with brom otrimethylsilane to give the target (E)-9-(3-phosphonomethoxypropen-1-yl) adenine. It was converted to the corresponding phosphonate diphosphate by reaction with bis(tributylammonium) pyrophosphate in the presence of 1,1'-carbonyldiimidazole. The substrate properties of the phosphonate towards human adenylate kinase were demonstrated.