Unsaturated fluoro-ketopyranosyl nucleosides: Synthesis and biological evaluation of 3-fluoro-4-keto-β- d-glucopyranosyl derivatives of N 4-benzoyl cytosine and N 6-benzoyl adenine

• Published in: European journal of medicinal chemistry Vol. 43; no. 2; pp. 420 - 428
• Main Authors: Manta, Stella, Agelis, George, Botić, Tanja, Cencič, Avrelija, Komiotis, Dimitri
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01-02-2008
• Subjects: Antitumor activity; Antiviral; Unsaturated fluoro ketonucleosides; β-Elimination reaction; Antiviral; Antitumor activity; β-Elimination reaction; Unsaturated fluoro ketonucleosides
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.04.001

The protected β-nucleosides 1-(2,4,6-tri-
O-acetyl-3-deoxy-3-fluoro-β-
d-glucopyranosyl)-
N
4-benzoyl cytosine (
2a) and 9-(2,4,6-tri-
O-acetyl-3-deoxy-3-fluoro-β-
d-glucopyranosyl)-
N
6-benzoyl adenine (
2b), were synthesized by the coupling of peracetylated 3-deoxy-3-fluoro-
d-glucopyranose (
1) with silylated
N
4-benzoyl cytosine and
N
6-benzoyl adenine, respectively. The nucleosides were deacetylated and several subsequent protection and deprotection steps afforded the partially acetylated nucleosides of cytosine
7a and adenine
7b, respectively. Finally, direct oxidation of the free hydroxyl group at 4′-position of
7a and
7b, and simultaneous elimination reaction of the β-acetoxyl group, afforded the desired unsaturated 3-fluoro-4-keto-β-
d-glucopyranosyl derivatives. These newly synthesized compounds were evaluated for their potential antitumor and antiviral activities. Compared to 5FU, the newly synthesized derivatives showed to be more efficient as antitumor growth inhibitors and they exhibited direct antiviral effect toward rotavirus.
We report the synthesis of three novel unsaturated fluoro-ketopyranosyl nucleosides (compounds
8a,
8b and
9a). Compared to 5FU, the newly synthesized derivates showed to be more efficient as antitumor growth inhibitors and they exhibited direct antiviral effect toward rotavirus.
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