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Highly Efficient Regioselective Synthesis of 5′-O-lauroyl-5-azacytidine Catalyzed by Candida antarctica Lipase B

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Abstract

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 °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.

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Acknowledgement

We acknowledge the National Natural Science Foundation of China (Grant No. 20676043), Science and Technology Project of Guangdong Province (Grant No. 2006A10602003; 2007B011000005), Science and Technology Project of Guangzhou (Grant No. 2007Z3-E4101), the Natural Science Foundation of Guangdong Province (Grant No. 05006571), the Doctoral Program of Higher Education (Grant No. 20070561080) and the Open Project Program of the State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (Grant No. N-06-06) for financial support.

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Authors and Affiliations

  1. Lab of Applied Biocatalysis, South China University of Technology, Guangzhou, 510640, China

    Xi-Yu Chen, Min-Hua Zong, Wen-Yong Lou & Hong Wu

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  1. Xi-Yu Chen
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  2. Min-Hua Zong
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  3. Wen-Yong Lou
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  4. Hong Wu
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Correspondence to Min-Hua Zong.

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Chen, XY., Zong, MH., Lou, WY. et al. Highly Efficient Regioselective Synthesis of 5′-O-lauroyl-5-azacytidine Catalyzed by Candida antarctica Lipase B. Appl Biochem Biotechnol 151, 21–28 (2008). https://doi.org/10.1007/s12010-008-8152-0

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