Abstract
Regioselective undecylenoylation of purine nucleosides as potential dual prodrugs was achieved by Candida antarctica lipase B using adenosine as a model reactant. The optimum organic solvent, molar ratio of vinyl ester to nucleoside, enzyme dosage, reaction temperature and molecular sieve amount were anhydrous THF, 5:1, 20 U/ml, 45°C and 75 mg/ml, respectively. Under the optimum conditions, the initial reaction rate, yield and 5′-regioselectivity were 1.1 mM/h, 90% and >99%, respectively. The enzymatic acylation of various nucleosides furnished the desired 5′-ester derivatives with the yields of 60–95% and 5′-regioselectivities of >99%. In addition, the lipase displayed excellent operational stability in THF, and retained 96% of its initial activity after reused for five batches.
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We are grateful for financial support of this work by the National Natural Science Foundation of China (20906032) and the Fundamental Research Funds for the Central Universities, SCUT (2009zz0018).
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Gao, WL., Li, N. & Zong, MH. Highly regioselective synthesis of undecylenic acid esters of purine nucleosides catalyzed by Candida antarctica lipase B. Biotechnol Lett 33, 2233–2240 (2011). https://doi.org/10.1007/s10529-011-0685-6
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DOI: https://doi.org/10.1007/s10529-011-0685-6