Preparation of nucleosides derived from 2-nitroimidazole and D-arabinose, D-ribose, and D-galactose by the Vorbrüggen method and their conversion to potential precursors for tracers to image hypoxia

J Org Chem. 2011 Oct 21;76(20):8159-67. doi: 10.1021/jo200727k. Epub 2011 Sep 9.

Abstract

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 °C to rt), catalyzed by triethylsilyl triflate (Vorbrüggen conditions). The α-anomer was formed in the former case and the β-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 Vorbrüggen 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 Vorbrüggen conditions enable a shorter route to azomycin nucleoside analogues than the previous coupling procedures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / chemistry
  • Animals
  • Arabinose / chemistry
  • Galactose / chemistry
  • Humans
  • Hypoxia / complications
  • Hypoxia / diagnosis*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Molecular Imaging / methods*
  • Neoplasms / complications
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nitroimidazoles / chemical synthesis*
  • Nucleosides / chemical synthesis*
  • Radioactive Tracers
  • Ribose / chemistry
  • Silanes / chemistry

Substances

  • Acetonitriles
  • Nitroimidazoles
  • Nucleosides
  • Radioactive Tracers
  • Silanes
  • Ribose
  • Arabinose
  • Galactose
  • acetonitrile