Phosphorylation of nucleosides

Any discussion of the prebiotic phosphorylation of nucleosides must take into account the probably neutral or alkaline conditions in a prebiotic environment. Some model phosphorylating systems have been studied, for example, the synthesis of /S-o-ribofuranose 1-phosphate from ribose and inorganic phosphate in the presence of cyanogen. Sodium trimetaphosphate will phosphorylate cw-glycols in good yield under alkaline... 

Various chlorophenoxyphosphorylditriazoles, prepared analogously to the phosphoryldiimidazoles from phosphordichloridate and triazole, are frequently used as reagents in the phosphorylation of nucleosides (see Chapter 12). 

Analogously, the corresponding tristriazolide of phosphoric acid was prepared from POCI3 and IV-trimethylsilyl-1,2,4-triazole in 60% yield.1261 Both trisazolides are used for the phosphorylation of nucleosides. 

Most kinases transfer chiral phospho groups with inversion and fail to catalyze partial exchange reactions that would indicate phosphoenzyme intermediates. However, nucleoside diphosphate kinase contains an active site histidine which is phosphorylated to form a phosphoenzyme.869 The enzyme catalyzes phosphorylation of nucleoside diphosphates other than ADP by a nucleotide triphosphate, usually ATP. 

It was later found that dialkyl(dialkylamino) phosphites (phosphoramidites, (RO)2PNR2 [114]), which are stable towards air and water and can be stored for longer, can readily be converted into the phosphinic chlorides (RO)2PCl by treatment with dimethylaniline hydrochloride, or into the corresponding tetrazolides by treatment with tetrazole. Tetrazolides (RO)2P-(l-tetrazolyl) had proven excellent reagents for the phosphorylation of nucleosides [113], and the treatment of phosphoramidites with alcohols in the presence of tetrazole was found to be a satisfactory method for the rapid preparation of trialkyl phosphites [115,116]. 

PhosphorylationThis reagent can be used for 3 -and/or 5 -phosphorylation of nucleosides in the phosphotriester approach to oligonucleotides. Deblocking by / -elimination proceeds cleanly with DBU in pyridine at 25" in 24 hours. 

Urea is another prebiotic condensing agent for the phosphorylation of nucleosides. Condensed phosphates have been obtained from ammonium phosphate and urea [126], while alcohols are easily phosphorylated at 150 °C by urea and phosphoric acid [127]. When an equimolar mixture of uridine 48 and Na2HP04 was heated at 100 °C in the presence of a ten-fold molar excess of urea and ammonium chloride, 97% of the phosphate was found to be incorporated into the nucleoside moiety mainly as uridine 5 -monophosphate 49 and uridine 2, 3 - cyclic phosphate 50 (Scheme 23). 

Schoffstall, A.M. 1976. Prebiotic phosphorylation of nucleosides in formamide. Origins Life Evol. Biosph. 7 399-412. 

Phosphorylation of nucleosides using the Yoshikawa procedure—synthesis of nucleoside 5 -monophosphates... 

The reagent is used for phosphorylation of nucleosides. It reacts with a free primary or secondary hydroxyl group to form a dibenzyl phosphate. Hydrogenation... 

Phosphorylation of nucleosides. This crystalline reagent is used to advantage in... 

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