A simple procedure for the synthesis of potential 6-azauridine prodrugs by Thermomyces lanuginosus lipase
A simple procedure for the synthesis of potential 6-azauridine prodrugs by Thermomyces lanuginosus lipase
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通过疏棉状嗜热丝孢菌脂肪酶合成潜在 6-氮杂苷前药的简单程序
DOI：
10.1016/j.molcatb.2009.03.002
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发表时间：
2009-07-01
影响因子：
--
通讯作者：
Zong, Min-Hua
中科院分区：
文献类型：
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作者：
Wang, Zhao-Yu;Li, Ning;Zong, Min-Hua
本文首次成功地研究了在热乳杆菌脂肪酶催化下，6-氮尿苷与脂肪酸乙烯酯的高选择性酰化反应，制备了5 ′-O-酰基衍生物。进一步考察了一些关键因素对6-氮杂尿苷棕榈酰化反应的影响。结果表明，最佳反应介质、反应温度和酶用量为无水丙酮、n（6-氮尿苷）：n（棕榈酸乙烯酯）= 1：7、反应温度为40 ℃、酶用量为450 U/ml，在此条件下，反应速率为13.3 mM/h，底物转化率为98.4%，区域选择性为99.0%。此外，在6-氮杂尿苷的区域选择性酰化反应中，该酶的酰基识别进行了研究。结果表明，尽管所有供试酰基供体都能得到6-氮杂尿苷的5 ′-O-酰基衍生物，但由于脂肪酶活性中心和酰基供体的结构不同，不同酰基供体的酶活性差异很大。(c)2009爱思唯尔有限公司版权所有。
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 degrees 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. (c) 2009 Elsevier B.V. All rights reserved.