Synthesis and biological activities of 2-pyrimidinone nucleosides. 2. 5-Halo-2-pyrimidinone 2'-deoxyribosides

Abstract
1-(2-Deoxy-.beta.-D-ribofuranosyl)-5-bromo-2-pyrimidinone (BrPdR) and 1-(2-deoxy-.beta.-D-ribofuranosyl)-5-iodo-2-pyrimidinone (IPdR) were synthesized by condensation of the appropriate silylated bases with 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-.alpha.-D-ribofuranosyl chloride in 1,2-dichloroethane in the presence of SnCl4, followed by separation of the anomeric blocked nucleosides via column chromatography and subsequent deprotection with methanolic ammonia. Both BrPdR and IPdR exhibited significant antiherpes activities against various strains of HSV-1 [herpes simplex virus type 1] and HSV-2, the latter compound (IPdR) showing the higher activity as well as the stronger binding to the virus-specific thymidine kinase.

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