Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis
A set of 3-deazauridine and 6-azauridine peracylated derivatives were regioselectively deacylated through Candida antarctica B lipase (CAL B) catalysed alcoholysis. This biotransformation provided an access to six new 2′,3′-di-O-acylated derivatives of 3-deazauridine and 6-azauridine carrying acetyl...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_13811177_v47_n1-2_p86_Zinni |
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todo:paper_13811177_v47_n1-2_p86_Zinni2023-10-03T16:11:45Z Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis Zinni, M.A. Iglesias, L.E. Iribarren, A.M. Enzymatic alcoholysis Lipase Nucleosides Prodrugs Regioselectivity Acylation Catalysis Derivatives Enzyme activity Regioselectivity Aqueous solubility Biotransformation Deacylation Nucleosides Prodrugs Drug products 3 deazauridine azauridine lipase B nucleoside derivative prodrug alcoholysis aqueous solution article biotransformation Candida antarctica deacylation drug solubility drug stability drug synthesis nonhuman stereochemistry Candida antarctica A set of 3-deazauridine and 6-azauridine peracylated derivatives were regioselectively deacylated through Candida antarctica B lipase (CAL B) catalysed alcoholysis. This biotransformation provided an access to six new 2′,3′-di-O-acylated derivatives of 3-deazauridine and 6-azauridine carrying acetyl, butanoyl or hexanoyl moieties, which were obtained in 80-99% yield. The regioselectivity displayed by CAL B towards 5′-O-acyl group removal agrees with the previously reported behavior of this enzyme in the acylation and deacylation of nucleosides. Log P, aqueous solubility and aqueous stability of these new diacylated compounds were determined, suggesting that the dibutanoylated and the dihexanoylated derivatives of 3-deazauridine and 6-azauridine could potentially act as prodrugs of the parent pharmacological active nucleosides. © 2007 Elsevier B.V. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_13811177_v47_n1-2_p86_Zinni |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Enzymatic alcoholysis Lipase Nucleosides Prodrugs Regioselectivity Acylation Catalysis Derivatives Enzyme activity Regioselectivity Aqueous solubility Biotransformation Deacylation Nucleosides Prodrugs Drug products 3 deazauridine azauridine lipase B nucleoside derivative prodrug alcoholysis aqueous solution article biotransformation Candida antarctica deacylation drug solubility drug stability drug synthesis nonhuman stereochemistry Candida antarctica |
| spellingShingle |
Enzymatic alcoholysis Lipase Nucleosides Prodrugs Regioselectivity Acylation Catalysis Derivatives Enzyme activity Regioselectivity Aqueous solubility Biotransformation Deacylation Nucleosides Prodrugs Drug products 3 deazauridine azauridine lipase B nucleoside derivative prodrug alcoholysis aqueous solution article biotransformation Candida antarctica deacylation drug solubility drug stability drug synthesis nonhuman stereochemistry Candida antarctica Zinni, M.A. Iglesias, L.E. Iribarren, A.M. Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| topic_facet |
Enzymatic alcoholysis Lipase Nucleosides Prodrugs Regioselectivity Acylation Catalysis Derivatives Enzyme activity Regioselectivity Aqueous solubility Biotransformation Deacylation Nucleosides Prodrugs Drug products 3 deazauridine azauridine lipase B nucleoside derivative prodrug alcoholysis aqueous solution article biotransformation Candida antarctica deacylation drug solubility drug stability drug synthesis nonhuman stereochemistry Candida antarctica |
| description |
A set of 3-deazauridine and 6-azauridine peracylated derivatives were regioselectively deacylated through Candida antarctica B lipase (CAL B) catalysed alcoholysis. This biotransformation provided an access to six new 2′,3′-di-O-acylated derivatives of 3-deazauridine and 6-azauridine carrying acetyl, butanoyl or hexanoyl moieties, which were obtained in 80-99% yield. The regioselectivity displayed by CAL B towards 5′-O-acyl group removal agrees with the previously reported behavior of this enzyme in the acylation and deacylation of nucleosides. Log P, aqueous solubility and aqueous stability of these new diacylated compounds were determined, suggesting that the dibutanoylated and the dihexanoylated derivatives of 3-deazauridine and 6-azauridine could potentially act as prodrugs of the parent pharmacological active nucleosides. © 2007 Elsevier B.V. All rights reserved. |
| format |
JOUR |
| author |
Zinni, M.A. Iglesias, L.E. Iribarren, A.M. |
| author_facet |
Zinni, M.A. Iglesias, L.E. Iribarren, A.M. |
| author_sort |
Zinni, M.A. |
| title |
Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| title_short |
Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| title_full |
Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| title_fullStr |
Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| title_full_unstemmed |
Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| title_sort |
preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis |
| url |
http://hdl.handle.net/20.500.12110/paper_13811177_v47_n1-2_p86_Zinni |
| work_keys_str_mv |
AT zinnima preparationofpotential3deazauridineand6azauridineprodrugsthroughanenzymaticalcoholysis AT iglesiasle preparationofpotential3deazauridineand6azauridineprodrugsthroughanenzymaticalcoholysis AT iribarrenam preparationofpotential3deazauridineand6azauridineprodrugsthroughanenzymaticalcoholysis |
| _version_ |
1807320013931020288 |