New procedure for the chlorination of pyrimidine and purine nucleosides

Abstract

The reaction between 1-B-D-arabinofuranosylcytosine hydrochloride (araC.HCl) and a slight molar excess of m-chloroperbenzoic acid (MCPBA) in an aprotic solvent such as dimethylformamide (DMF), dimethylacetamide (DMA), or hexamethylphosphorus triaide was examined. Chromatographic evaluation of the reaction mixture showed two major components, unreacted starting material, and a reaction product having a slightly greater R/sub f/ value. The reaction between MCPBA and other pyrimidine and purine derivatives in dipolar aprotic solvents containing HCl was investigated. In the pyrimidine series both uracil and cytosine derivatives gave the corresponding 5-chloro derivatives in high yield after a facile workup. Application of the same reaction conditions to the purine derivatives adenosine and guanosine gave the 8-chloro nucleosides in good yield, thus producing 8-chlorogyanosine. The product 9-B-D-arabinofuranosyl-8-chloroadenine was obtained when the reaction was applied to the potent antiviral agent 9-B-D-arabinofuraosyladenine. The new chlorination method gives good to excellent yields, short reaction times, mild reaction conditions and ready availability of starting materials. 1 table. (DP)