SYNTHESIS OF NOVEL 6-AZAPYRIMIDINE 2′(3′)-FLUORODEOXY NUCLEOSIDES
Abstract
Fluorinated nucleosides have been shown to possess interesting physicochemical and biological properties. Bioisosteric replacement of a hydroxy group or a hydrogen atom by fluorine atom(s) is a classic approach in medicinal chemistry
to improve the pharmacological properties of a biologically active molecule. Essential modifications that led to the discovery of fluorinated nucleosides with biological activity are substitutions at 2′- and 3′-positions deoxy-furanosyl moiety. Novel 6-azathymine 2′(3′)-fluorodeoxy nucleosides have been prepared by the silyl method starting from persilylated 6-azathymine and 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-α,β-D-ribofuranose or 3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabino-furanosyl bromide. Debenzoylation of protected 6-azathymine 2′(3′)-fluorodeoxy nucleosides with methanolic ammonia resulted in the corresponding fluorinated nucleosides in good yields. Along with the main products of the deprotection, their 5′-O-benzoyl derivatives were isolated. Conversion of the 6-azathymine 2′(3′)-fluorodeoxy nucleosides into 5-methyl-6-azacytosine 2′(3′)-fluorodeoxy nucleosides was accomplished via the corresponding 4-thioderivatives. The structures of all synthesized nucleosides were proved by UV-, NMR- and mass-spectroscopy. Novel 6-azapyrimidine 2′(3′)-fluorodeoxy nucleosides are of interest as potential antiviral and anticancer agents.
to improve the pharmacological properties of a biologically active molecule. Essential modifications that led to the discovery of fluorinated nucleosides with biological activity are substitutions at 2′- and 3′-positions deoxy-furanosyl moiety. Novel 6-azathymine 2′(3′)-fluorodeoxy nucleosides have been prepared by the silyl method starting from persilylated 6-azathymine and 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-α,β-D-ribofuranose or 3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabino-furanosyl bromide. Debenzoylation of protected 6-azathymine 2′(3′)-fluorodeoxy nucleosides with methanolic ammonia resulted in the corresponding fluorinated nucleosides in good yields. Along with the main products of the deprotection, their 5′-O-benzoyl derivatives were isolated. Conversion of the 6-azathymine 2′(3′)-fluorodeoxy nucleosides into 5-methyl-6-azacytosine 2′(3′)-fluorodeoxy nucleosides was accomplished via the corresponding 4-thioderivatives. The structures of all synthesized nucleosides were proved by UV-, NMR- and mass-spectroscopy. Novel 6-azapyrimidine 2′(3′)-fluorodeoxy nucleosides are of interest as potential antiviral and anticancer agents.
About the Authors
T. S. Bozhok
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Senior Researcher
Belarus
Senior Researcher
E. N. Kalinichenko
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Corr. Member, Dr. Sc. (Chemistry), Deputy Director for scientific activity and innovations.
Belarus
Corr. Member, Dr. Sc. (Chemistry), Deputy Director for scientific activity and innovations.
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