- New non-aromatic triazinic nucleosides : Synthesis and antiretroviral evaluation of β-ribosylamine nucleoside analogs
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Various 5-alkyl-6-aza-5,6-dihydrouridines and 6-(β-D-ribopyranosyl)-5-alkyl-6-aza-5,6-dihydrouracils have been synthesized. A new regioselective method is described for coupling triazinic bases to the sugar unit. Different epimers were isolated. Antiretroviral activity against Visna virus was evaluated.
- Depelley, Jean,Granet, Robert,Kaouadji, Mourad,Krausz, Pierre,Piekarski, Salomon,Delebassee, Sylvie,Bosgiraud, Claudine
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p. 995 - 1008
(2007/10/03)
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- Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine
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Purpose. The purposes were to study the kinetics of hydrolysis of 2',3',5'-triacetyl-6-azauridine (1) in aqueous solution (μ = 0.5) and to identify the main intermediates and products of the reaction. Methods. A stability indicating isocratic LC assay was used to study the rate of degradation of 1. A gradient LC assay was used to study the time courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by 1H-NMR and CI-MS. The pK(a) value was obtained by potentiometric titration. Results. At 36.8°C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine. Conclusions. A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.
- Riley,Mummert,Zhou,Schowen,Vander Velde,Morton,Slavik
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p. 1361 - 1370
(2007/10/03)
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- 2',3'-O-CARBONYL DERIVATIVES OF 6-AZAURIDINE IN THE SYNTHESIS OF ITS 5'-SUBSTITUTED AND 5'-DEOXY DERIVATIVES
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Preparation of 2',3'-O-carbonyl derivatives of 5'-deoxy-6-azauridine and 6-azauridine using 1,1'-carbonyldiimidazole has been elaborated. 5'-Chloro and 5'-bromo derivatives were prepared by treatment of the 5'-O-mesyl derivative with quarternary ammonium halides, 5'-chloro derivatives also by direct halogenation with thionyl chloride in hexamethylphosphortriamide or with tetrachloromethane, triphenyl phosphine, and dimethylformamide.Derivatives of 5'-bromo-6-azauridine were reduced with tributyltin hydride to 5'-deoxy-6-azauridine compounds. 6-Azauridine 2',3'-carbonate (IVa) and its 5'-derivatives IVc and IVe on treatment with imidazole in dimethylformamide afforded 2,2'-anhydronucleosides IIIa-IIIc.The 2,2'-anhydro-5'-deoxy compound IIIc underwent alkaline hydrolysis to 5'-deoxy-1-β-D-arabino-pentofuranosyl-6-azauracil (VIa).Treatment of 2,2'-anhydro-5'-deoxy-5'-chloro derivative IIIb with hydrogen chloride led to 2',5'-dichloro derivative If.
- Drasar, Pavel,Beranek, Jiri
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p. 2070 - 2082
(2007/10/02)
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