Highly efficient regioselective synthesis of 5′-O-lauroyl-5-azacytidine catalyzed by Candida antarctica lipase B
Highly efficient regioselective synthesis of 5′-O-lauroyl-5-azacytidine catalyzed by Candida antarctica lipase B
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DOI：
10.1007/s12010-008-8152-0
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发表时间：
2008-10-01
影响因子：
3
通讯作者：
Wu, Hong
中科院分区：
文献类型：
--
作者：
Chen, Xi-Yu;Zong, Min-Hua;Wu, Hong
首次用固定化的B型假丝酵母脂肪酶(即Novozym 435)成功地实现了5-氮杂胞苷与月桂酸乙烯酯的区域选择性酰化反应。5-氮杂胞苷的酰化反应发生在伯羟基，反应速度快、转化率高、区域选择性好，可制得目标产物5‘-O-月桂酰基-5-氮杂胞苷。系统考察了几个关键因素对酶促酰化反应的影响。结果表明，吡啶为最佳反应介质。最佳初始水活度、月桂酸乙烯酯与5-氮杂胞苷的摩尔比和反应温度分别为0.07、30：1和50℃。在上述优化条件下，反应5h左右，初始反应速率、底物转化率和区域选择性分别高达0.58 mm/min、95.5%和99%。
Enzymatic regioselective acylation of 5-azacytidine with vinyl laurate was successfully conducted with an immobilized lipase from Candida antarctica type B (i.e., Novozym 435) for the first time. The acylation of 5-azacytidine took place at its primary hydroxyl group and the desired product 5 '-O-lauroyl-5-azacytidine could be prepared with high reaction rate, high conversion, and excellent regioselectivity. The influences of several key variables on the enzymatic acylation were also systematically examined. Pyridine was found to be the best reaction medium. The optimum initial water activity, the molar ratio of vinyl laurate to 5-azacytidine and reaction temperature were 0.07, 30:1, and 50 degrees C, respectively. Under the optimized conditions described above, the initial reaction rate, the substrate conversion, and the regioselectivity were as high as 0.58 mM/min, 95.5%, and > 99%, respectively, after a reaction time of around 5 h.