Preparation of Nucleosides Derived from 2-Nitroimidazole and D-Arabinose, D-Ribose, and D-Galactose by the Vorbruggen Method and Their Conversion to Potential Precursors for Tracers To Image Hypoxia

2-Nitroimidazole was silylated using hexaethyldisilazane and then reacted with 1-O-acetyl derivatives of D-arabinose, D-ribose, and D-galactose in acetonitrile at mild temperatures (-20 degrees C to rt), catalyzed by triethylsilyl triflate (Vorbruggen conditions). The alpha-anomer was formed in the former case and the beta-anomers in the latter two cases (highly) selectively. When D-arabinose and D-ribose were silylated with tert-butyldiphenylsilyl chloride in pyridine at the hydroxyl groups at C-5 and acetylated at the other ones in a one-pot reaction, mixtures of anomeric 1-O-acetyl derivatives were obtained. These were coupled by the Vorbruggen method and then deblocked at C-5 and tosylated to give precursors for tracers to image hypoxia in four steps without using Hg(CN)(2) necessary for other methods. The Vorbruggen conditions enable a shorter route to azomycin nucleoside analogues than the previous coupling procedures.