This unit describes a method for preparing nucleoside polyphosphates and their conjugates such as nucleoside triphosphates, symmetrical and unsymmetrical dinucleoside polyphosphates and sugar nucleotides. The protocols employ sulfonyl imidazolium salts (SnISs) as coupling reagents. These reagents are prepared in two steps in very high yield from commercially available materials and can be stored for at least 1 year at -20°C. The tetra-n-butylammonium salts of nucleoside mono-, di-, or triphosphates are reacted with the SnISs to form reactive phosphoryl imidazolium donors. These donors are reacted with the tetra-n-butylammonium salts of pyrophosphate, nucleotide mono- or diphosphates or sugar-1-phosphates to give the nucleoside polyphosphates and their conjugates in excellent yields.
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