Pyrophosphate triesters

The chemical synthesis of mono-, di-, tri-, and tetraphosphates usually starts with unprotected nucleosides to produce posphoamidates at first. The monophosphate may be treated either with morpholine and DCC to afford the phosphoro-morpholidate or with carbonyl bis(imidazole) to yield the phosphor imidazolidate. A third method uses diphenylphosphorochloridate to give a pyrophosphate triester (Scheme 8.5.10). All three intermediates react with orthophosphate, diphosphate, or ATP to yield di-, tri-, or tetraphosphates, respectively. 

S-2-carbamoylethyl thiophosphate can be activated with diphenyl phosphorochloridate and the resulting pyrophosphate triester reacted wdth a nucleoside diphosphate to give a... 

In the 1,3,2-dioxaphosphole method a bis(2-butene-2,3-diyl) pyrophosphate is used as the condensing agent. It allows two successive esterifications of one phosphate group to be performed without additional activation. First a 5 -O-protected nucleoside is added in methylene chloride in the second reaction an unprotected nucleoside can be used, since only the 3 OH group is able to attack the cyclic enediol 3 -nucleosidyl phosphotriester. Protected dinucleoside triesters are obtained in 80% yield. Removals of protective groups, methoxytrityl by means of trifluoroacetic acid in methylene chloride and 1-methylacetonyl by aqueous triethyl-amine, also give about 80% yield (F. Ramirez, 1975, 1977). 

Pyrophosphate esters can be obtained by heating dialkyl halophosphates with triesters (5.311) or dialkyl sodinm salts (5.312) (Table 5.26). 

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