A simple procedure for the synthesis of potential 6-azauridine prodrugs by Thermomyces lanuginosus lipase

Highly regioselective acylation of 6-azauridine with fatty acid vinyl esters catalyzed by the lipase from Thermomyces lanuginosa for the preparation of its 5′-O-acyl derivatives has been successfully performed for the first time. The effects of some crucial factors on the enzymatic palmitoylation of 6-azauridine were further examined. The optimum reaction medium, molar ratio of 6-azauridine to vinyl palmitate, reaction temperature and enzyme dosage were found to be anhydrous acetone, 1:7, 40 °C and 450 U/ml, under which the reaction rate, the substrate conversion and the regioselectivity were 13.3 mM/h, 98.4% and 99.0%, respectively. Moreover, the acyl recognition of the enzyme in the regioselective acylation of 6-azauridine was investigated. The results showed that although 5′-O-acyl derivatives of 6-azauridine were exclusively obtained with all the tested acyl donors, the enzymatic activity varied widely with different acyl donors owing to the specific structures of the lipase's active site and the acyl donors.