Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine

Article abstract of DOI:10.1023/A:1016238110533

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.