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| A mild, ef?cient and regioselective enzymatic procedure has been successfully conducted for the synthesis of 5'-O-palmitoyl-?uorouridine, a potential prodrug of 5-?uorouridine, from 5-fluorouridine and vinyl palmitate with Lipozyme TL IM in acetone-THF (85/15, v/v) co-solvent mixture. Addition of molecular sieves into the reaction mixture can effectively removed the water, which was proved to cause the hydrolysis of a large amount of acyl donors, thus greatly lowering the acyl donors used. In the presence of molecular sieves, the optimal molar ratio of vinyl palmitate to 5-FUR, enzyme dosage, temperature and shaking rate were 2:1, 15 mg/ml, 40 ℃ and 200 r/min, respectively, under which the initial reaction rate, yield and regioselectivity were 12.3 mM/h, 98.6% and >99%, respectively after 8 hours. Moreover, Lipozyme TL IM displayed a good operational stability and 96.3% of its original activity was maintained after being reused for 10 cycles. |
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| Keywords:5-Fluorouridine; Lipozyme TL IM; Regioselective Palmitoylation; Co-solvent mixture |
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