Halogen-substituted nucleosides have been utilized as intermediates for a variety of synthetic transformations. We now present a general procedure for bromination at C-5 of pyrimidine and C-8 of purine nucleosides with 1,3-dibromo-5,5-dimethylhydantoin (DBDMH). Treatment of uridine, cytidine, adenosine or guanosine with DBDMH in DMF at ambient temperature (0.5 � 24 h) and crystallization of the crude reaction mixtures gave the corresponding 5- or 8-bromo substituted nucleosides (40-76%). Treatment of the protected nucleosides including 2'-deoxyuridine and 1-(�,D-arabinofuranosyl)uracil with DBDMH in CH2Cl2 (1.5  - 24 h) at ambient temperature also produced C-5 or C-8 brominated nucleosides (51-95%) with purity >90% after only aqueous work-up. Combination of DBDMH with Lewis acids (e.g. TMSOTf, TsOH) resulted in better yields and shorter reaction times. Bromination with DBDMH is compatible with typical protection groups use in nucleoside chemistry (acyl, silyl, isopropylidene). Effects of temperature, time, solvent and acid catalysts on the bromination reaction will be discussed.

Bromination at C-5 of pyrimidine and C-8 of purine nucleosides with 1,3-dibromo-5, 5-dimethylhydantoin

243rd National Meeting (2012)

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