Preparation of 1-α-D-Arabinofuranosylbenzimidazole and Its 5,6-Dichloro Derivative, and the Direct Bromination of Benzimidazole Nucleosides

Abstract

Abstract Arabinofuranosyl Benzim idazole N ucleosides, Direct Bromination of Benzim idazole N ucleosides, 1H NMR Spectroscopy, Ultraviolet Spectra The 1-a-D-arabinofuranosides of benzim idazole and 5,6-dichlorobenzim idazole, analogues of the biologically active 5,6-dichloro-l-β-D-ribofuranosylbenzimidazole, have been synthesized by condensation of the trimethylsilyl derivative of the appropriate benzim idazole in the presence of SnCl4 with 1-O-m ethyl-2,3,5-tribenzoyl-a-D-arabinoside.The 5(6)-m onobrom o and the 5,6-dibrom o derivatives of 1-β-D-ribofuranosylbenzimidazole and 1-α-D-arabinofuranosylbenzimidazole were then prepared by direct bromination of the latter. With 1-β-D-ribofuranosylbenzimidazole, the initial product of bromination was a 1:1 mixture of the 5-bromo and 6 -brom o derivatives; the final product was the desired 5,6-dibromo analogue. In the case of 1-αβ-D-arabinofuranosylbenzimidazole, the initial product of bromination was the 5-(or 6 -)brom o derivative, and the 5,6-dibrom o derivative the final product. The monobrom o derivatives were easily separated from the dibrom o by chromatography on Am berlite XAD-4. Identification of all of these was based on several criteria, including detailed analyses of the 1H NMR spectra.The benzim idazole nucleoside are considerably m ore resistant to acid hydrolysis than the cor­ responding purine nucleosides. The effects of halogenation on the ultraviolet absorption spectra of the benzim idazole nucleosides are described.