New procedure for the chlorination of nucleic acid bases and their nucleosides

Abstract

Four nucleic acid bases and their nucleosides were chlorinated by acyl chloride in dimethylformamide and m-chloroperbenzoic acid(MCPBA). The reaction of bases or nucleosides with MCPBA and acyl chlorides in dimethylformamide shows that under such conditions N-oxidation and chlorination of the primary hydroxyl group was not observed and the major product obtained was from the chlorination of heterocyclic bases. In the absence of MCPBA, the reaction took place the chlorination of 5``-hydroxy group of nucleosides. In the pyrimidine series, the product was the 5-chlorinated derivative and in the purine series, the 8-chlorinated analog was formed. In addition, other halide ion sources that could make complexes with dimethylformamide were investigated. 5-Bromouridine was also synthesized by using phosphorous tribromide in analogous manner. The halogenated compounds thus obtained were all separated by using silica gel column except for the 5-chlorouracil, and their structures or purities were characterized by the physical (mp, TLC) and spectroscopic (UV, NMR, HPLC) methods. Application and limitation of the chlorination reaction is discussed as well as mechanistic implications.