Nucleoside Triphosphates and Their Analogues

133 Nucleoside Triphosphates and Their Analogues. - A review has been given of the most useful methods for the synthesis of nucleoside triphosphates. 5 -Triphosphates of 8-(alkylthio)adenosines have been prepared as inhibitors of nucleoside triphosphate diphosphohydrolase, and the triphosphates 202 and that derived from 2,2 -anhydrouridine have been made as agonists for P2X2-purinoceptors, but they showed lesser potencies than the parent nucleosides. Derivatives of ATP, UTP and CTP have been prepared in which methyl ketone groups are attached via spacers to the base units, in order to permit interaction with fluorescent probes after enzymic incorporation into oligonucleotides. The triphosphate was assembed by Eckstein s procedure, in which a 2, 3 -0-iso-propylidene nucleoside is treated sequentially with salicyl phosphorochloridite, pyrophosphate and an oxidant.  

Reduction of ATP to the 2 -deoxy-compound has been carried out on a preparative scale using recombinant Lactobacillus leichmannii ribonucleotide triphosphate reductase.  

The 3 -0-phosphonomethyl compound 203 has been prepared by alkylation of 0-3 of thymidine, and was converted into the triphosphate analogue 204 by reaction with tributylammonium pyrophosphate, previously activated by car-bonyldiimidazole. Initial reaction of 203 with carbonyldiimidazole led to the formation of a dimeric pyrophosphonate of 203. Similar chemistry was also carried out on a-thymidine, and the substrate properties of the products 203 and its a-anomer towards DNA polymerases were studied.  

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