5-氟尿苷5'-棕榈酸酯的酶法合成

Enzymatic Synthesis of 5'-Palmitate of 5-Fluorouridine

考察了10ml丙酮-四氢呋喃(85/15,体积比)混合溶剂体系中,各关键因素对脂肪酶LipozymeTLIM催化5-氟尿苷5'-棕榈酸酯合成反应的影响.结果表明,添加分子筛能有效除去溶剂中的水分,从而极大地提高了目标产物收率.在最优反应条件下,该体系被成功放大至200ml(5-氟尿苷克级用量),产物收率高达99%;同时脂肪酶LipozymeTLIM表现出优异的操作稳定性,重复使用10批次后,产物收率仍可达97%.另外,填充床反应器的体积生产效率为22.4g/(L·h),远高于批次反应时的0.5g/(L·h).

In a 10 ml co-solvent system of acetone-THF （85/15, volume ratio）, the effects of key parameters on the synthesis of 5＇-palmitate of 5-fluorouridine （5-FUR） catalyzed by Lipozyme TL IM were investigated. It was revealed that water in the mixture could be removed efficiently by adding molecular sieves, thus significantly improving the yield of the desirable product. The batch enzymatic reaction was successfully scaled up to 200 ml （1 g 5-FUR scale）, furnishing a yield of 99%. Moreover, Lipozyme TL IM displayed excellent operational stability in this reaction system. The yield of 97% was obtained after reuse for 10 cycles. Additionally, the volumetric productivity in a packed bed reactor for the synthesis of 5＇-O-palmitoyl-5-FUR was 22.4 g/（L·h）, which was much higher than that in the batch reactor （0.5 g/（L·h））.