Dioxane diphosphate

Phosphorylation. Chambers et al. found the reagent useful for the preparation of nucleoside diphosphoric acids (3, R —adenine, uracil, etc.). A nucleotide (I) is converted into the 5 -phosphoramidate (2) by reaction with ammonia and dicyclo-hexylcarbodiimide (DCC), and the amidate (2) is treated with dioxane diphosphate in o-chlorophenol (3 hrs..0 ). The diphosphoric acid (3) is precipitated with petroleum ether and purified as the ammonium salt. Yields are around 90%, whereas when 8.5% phosphoric add was used yields were in the order of 50-60%. However, anhydrous... 

Phosphorylation O-Benzyl phosphorus 0,0-diphenylphosphoric anhydride. 2-Cyanomethyl phosphate. Dibromomalonamide. Di-p-nilrobenzylphosphoryl chloridate. Dioxane diphosphate. Diphenylphosphorochloridate. Ethoxyacetylene. Metaphosphoric acid. o-Phenyl-ene phosphorochloridate. Phosphoric acid, anhydrous. Phosphorodimorpholidic chloride. Phosphorus pentoxide-Phosphoric acid. Phosphoryl chloride. Polyphosphoric acid. Pyro-phosphoryl tetrachloride. Silver dibenzyl phosphate. Silver diphenyl phosphate. Tetra-p-nitrophenyl pyrophosphate. 

It now remained for us to apply the Coward protocol to our system and complete the synthesis of lipid I. Thus, phosphate 26 [Scheme 10], prepared by reductive cleavage of the phosphodiester protective groups of 9 (H2, Pd/C in MeOH, followed by pyridine, 91% yield), was converted to the corresponding phosphoroimidazolidate, whose formation was readily monitored via mass spectrometry. Excess carbonyldiimidazole was quenched via addition of methanol. The lipid phosphate salt was then added in portions via syringe until complete consumption of the phosphoroimidazolidate intermediate was observed. Mass spectrometry also allowed us to monitor the appearance of the desired lipid-linked diphosphate product. When the reaction was judged to be complete, the reaction solution was carefully concentrated and the crude product was treated with sodium hydroxide in aqueous dioxane in order to achieve global deprotection. The crude product was purified by reverse-phase... 

Dry dicyclohexylguanidinium adenosine 5 -phosphoramidate and dry dioxane diphosphoric acid dissolved in o-chlorophenol, and stirred rapidly at 0 for 3 hrs. adenosine 5 -diphosphate. Y 83%.—Rigidly anhydrous conditions are necessary and during humid weather the dissolution is performed in a dry box. Dioxane diphosphoric acid is a convenient source of anhydrous phosphoric acid . F. e. s. R. W. Chambers, P. Shapiro, and V. Kurkov, Am. Soc. 82, 970 (1960). 

Estrone-3-phosphoric acid allowed to react with diphenylphosphorochloridate in anhydrous dioxane in the presence of tri-n-hutylamine, and the resulting anhydride treated with 1.2 moles of adenosine-5 -monophosphate in pyridine P-adenosine P -estrone diphosphate, Y 90%.—Of several methods tested the above one gives the best yields. F. e. s. J. Riess and G. Ourisson, Bl. 1961, 1243 method s. A. M. Michelson, Chem. Ind. 1960, 1267. 

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