Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene ("1,3-dideazauridine").
In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.
D015092:3-Deazauridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005260:Female; D007939:Leukemia L1210 / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D014529:Uridine / Q000031:analogs & derivatives*
D015092:3-Deazauridine; C010442:1,3-dideazauridine; D014529:Uridine