Fluoro-ketopyranosyl nucleosides: Synthesis and biological evaluation of 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives of N-4-benzoyl cytosine

Abstract

1,2:5,6-Di-O-isopropylidene-ot-D-glucofuranose on mild oxidation, reduction, fluorination, and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-D-glueopyranose. This was coupled with silylated N-4-benzoyl cytosine. The nucleoside was deacetylated and after several subsequent protection and deprotection steps afforded the desired 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives. These novel synthesized compounds were evaluated for antiviral and cytotoxic activities against rotavirus, vesicular stomatitis virus, and the human colon adenocarcinoma cell line Caco-2, and have a promising potential in combating the rotaviral infections and in the treatment of colon cancer. As compared to AZT, a nucleoside analogue of reverse transcriptase inhibitor, the novel synthesized 1-(3,4-dideoxy-3-tluoro-beta-D-glycero-hex-3-enopyranosyl-2-ulose)-N-4-benzoyl cytosine showed to be more effective at lower concentrations in inhibition of rotavirus infection as well as in the same range of antitumor activity. (c) 2006 Elsevier Ltd. All rights reserved.