Preparation of potential 3-deazauridine and 6-azauridine prodrugs through an enzymatic alcoholysis

• Language: unknown
• Published: 2007
• Subjects: Enzymatic alcoholysis; Lipase; Nucleosides; Prodrugs; Regioselectivity; Acylation; Catalysis; Derivatives; Enzyme activity; Aqueous solubility; Biotransformation; Deacylation; Drug products; 3 deazauridine; azauridine; lipase B; nucleoside derivative; prodrug; alcoholysis; aqueous solution; article; Candida antarctica; drug solubility; drug stability; drug synthesis; nonhuman; stereochemistry; Antarc*; Antarctica
• Online Access: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13811177_v47_n1-2_p86_Zinni; https://hdl.handle.net/20.500.12110/paper_13811177_v47_n1-2_p86_Zinni

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.