Nucleosides with phosphorus-based reagents

Phosphorus oxychloride is a suitable reagent for preparation of the symmetrically substituted phospho-triesters of type (RO)3PO. The preparation is easily achieved by treatment of phosphorus oxychloride with 3 equiv. of alcohols or their metal salts. The reaction is generally promoted by a base or acid. Titanium trichloride is a particularly effective catalyst for the reaction. Conversion of POCI3 to unsymmetri-cally substituted phosphotriesters is achievable with difficulty. Phosphorochloridates and phosphorodichloridates have been used for the preparation of mixed tertiary phosphoric esters of type (ROlmPOfOROn (ffi = 1, n = 2, or m = 2, n = 1) in a very wide variety. Reaction of phosphorus oxychloride and 1 or 2 equiv. of alcohols followed by hydrolysis forms phosphomonoesters or phosphodi-esters, respectively. The hydrolysis may be generally effected by dilute aqueous alkali. Some phosphoFodichlori te intermediates are easily hydrolyzed by water. For example, the phosphorylation of a ribonucleoside (1 equation 4) with phosphorus oxychloride in an aqueous pyridine-acetonitrile mixture furnishes the nucleoside S -monophosphate (2) in excellent yield. ... 

The main agent used for the conversion of oxopurine into chloropurines is phosphoryl chloride, either alone or with added water (which may produce pyrophosphoryl chloride), phosphorus pentachloride, or with bases, usually tertiary amines and especially W,W-dimethyl- or diethyl-aniline. The use of bases, especially aliphatic amines, may however lead to introduction of dialkyamino groups into the purine or formation of other byproducts (74RCR1089). Other reagents which have been used include (a) thionyl chloride in DMF (Vilsmeier-Haak reagents) which converts 2, 3, 5 -tri-0-benzoylinosine into the 6-chloropurine nucleoside (64CPB639) and (b) chloromethylenedimethylammonium chloride in chloroform. 

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