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Synthesis of 2′,3′‐Dideoxy‐2′‐fluoro‐3′‐(hydroxyimino)‐, ‐3′‐(methoxyimino)‐ and ‐3′‐(hydroxyamino)pyrimidine Nucleosides
Author(s) -
Khalil Ahmed,
Mathé Christophe,
Périgaud Christian
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200119
Subject(s) - chemistry , pyrimidine , stereochemistry , cytidine , oxime , two dimensional nuclear magnetic resonance spectroscopy , nucleoside , medicinal chemistry , organic chemistry , enzyme
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 1 H and 19 F NMR spectroscopic analysis. In particular, we observed striking differences in 19 F 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).