65174-95-0Relevant articles and documents
Baker et al.
, p. 273,276 (1979)
Enzymatic regioselective and complete deacetylation of two arabinonucleosides
Sabaini, Maria B.,Zinni, Maria A.,Mohorcic, Martina,Friedrich, Jozefa,Iribarren, Adolfo M.,Iglesias, Luis E.
experimental part, p. 225 - 229 (2010/11/02)
Candida antarctica lipase B (CAL-B)-catalysed regioselective deacetylation of 2′,3′,5′-tri- O-acetyl-1-β- d-arabinofuranosyluracil (1) and 2′,3′,5′-tri- O-acetyl-9-β- d-arabinofuranosyladenine (2) was studied. The choice of the reaction medium allowed the regioselective formation of products bearing different degree of acetylation: in isopropanol, CAL-B catalysed the formation of the corresponding 2′- O-acetylated arabinonucleosides, while hydrolyses afforded the 2′,3′-di- O-acetylated products. In particular, the procedure herein described allows a simple and efficient preparation of the reported vidarabine prodrug 2′,3′-di- O-acetyl-9-β- d-arabinofuranosyladenine, avoiding the utilisation of protective groups. Moreover, to achieve full deacetylation of the assayed substrates, a set of commercial hydrolases and fungal keratinases from Doratomyces microsporus (DMK) and Paecilomyces marquandii (PMK) were tested. While only PMK and DMK catalysed the quantitative complete deacetylation of 1, DMK accomplished full deacetylation of 2 in shorter time than the other assayed enzymes.
Hydrolysis and solvent-dependent 2'→5' and 3'→5' acyl migration in prodrugs of 9-β-D-arabinofuranosyladenine
Anderson,Fung,Kumar,Baker
, p. 825 - 830 (2007/10/02)
As a prerequisite to quantitative in vivo studies to further explore the promising topical activity of the 2',3'-di-O-acetyl derivative of 9-β-D-arabinofuranosyladenine (ara-A) against herpes virus infections, the kinetics of solution degradation of the 2',3'-di-O-acetyl derivative and the 2'-, 3'-, and 5'-monoacetates were investigated. The rates of aqueous solution hydrolysis were found to be consistent with rank order predictions based on a consideration of substituent effects. Preliminary in vivo hydrolysis data, however, do not correlate with such predictions, indicating a need for more systematic studies of the effect of molecular structure on enzyme-catalyzed hydrolysis. An important reaction of the 2',3'-diester and the 3'-monoester in aqueous solution, in addition to ester hydrolysis, is 3'→5' acyl migration. 2'→5' Acyl migration does not occur in water but is the predominant migration pathway in organic solvents, as verified by studies in acetonitrile. 1H NMR spectroscopy was employed to study the dependence of the conformation of the sugar ring on the solvent environment. Although a change in the equilibrium between the C(2')endo and C(3')endo conformational states does occur, it is not a dramatic change and cannot explain the solvent selectivity observed in the acyl migration kinetics.
