School of Life Science and Chemical Engineering, Huaiyin Institute of Technology, Huai'an 223003, People's Republic China.
Appl Biochem Biotechnol. 2011 Nov;165(5-6):1161-8. doi: 10.1007/s12010-011-9333-9. Epub 2011 Aug 6.
3'-O-Acyl-trifluridines were prepared successfully through an enzymatic approach for the first time. Among the ten commercially available lipases tested, Pseudomonas cepacia lipase displayed the highest regioselectivity towards the acylation of 3'-hydroxyl of trifluridine. Furthermore, the effects of some crucial factors on the enzymatic myristoylation of trifluridine were examined. The optimal reaction medium, molar ratio of trifluridine to vinyl myristate and reaction temperature were found to be anhydrous THF, 1:7 and 50 °C, under which the reaction rate, substrate conversion, and 3'-regioselectivity were 63.9 mM/h, >99.0%, and 99%, respectively. Additionally, the enzyme recognition of the chain length of the acyl donors was investigated. The results showed that 3'-regioselectivity of the enzyme maintained 99% with the increment of acyl chain length (C6, C10, and C14). The reason might derive from the strong hydrophobic interaction between 5-CF(3) group of the base moiety and Leu 287 located in the medium-sized pocket of the active site.
3'-O-酰基三氟尿苷首次通过酶法成功制备。在测试的十种市售脂肪酶中，假单胞菌脂肪酶对三氟尿苷 3'-羟基的酰化具有最高的区域选择性。此外，还研究了一些关键因素对三氟尿苷酶法豆蔻酰化的影响。发现最佳反应介质、三氟尿苷与乙烯基豆蔻酸的摩尔比和反应温度分别为无水 THF、1:7 和 50°C，在此条件下，反应速率、底物转化率和 3'-区域选择性分别为 63.9mM/h、>99.0%和 99%。此外，还研究了酶对酰供体链长的识别。结果表明，随着酰链长度的增加（C6、C10 和 C14），酶的 3'-区域选择性保持在 99%。原因可能源于碱基部分的 5-CF3 基团与位于活性位点中号口袋中的亮氨酸 287 之间的强疏水性相互作用。
