Synthesis of 2',3'-dideoxy-2'-fluoro-3'-(hydroxyimino)-, -3'-(methoxyimino)- and -3'-(hydroxyamino)pyrimidine nucleosides

Abstract

New series of 2',3'-dideoxy-2'-fluoro-3'-(hydroxyimino)-, -3'-(methoxyimino)- and -3'-(hydroxyamino)pyrimidine nucleosides were synthesized. Structural assignments of the former two derivatives, which were obtained as inseparable mixtures of (E) and (Z) isomers, were based upon 1H and 19F NMR spectroscopic analysis. In particular, we observed striking differences in 19F NMR spectra resulting from through-space N-F coupling for compounds having proximate nitrogen (oxime) and fluorine atoms with lone-pairs correctly oriented for overlapping. Antiviral and cytotoxic activities of the target nucleosides were evaluated; however, none of them showed any antiviral activity. Only 2',3'-dideoxy-2'-fluoro-3'- (hydroxyamino)cytidine (19) showed moderate activity against the proliferation of murine leukemia cells (L1210). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.