Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (6): 1154-1160.DOI: 10.6023/cjoc201401024 Previous Articles     Next Articles



夏然a,b, 郭真b, 秦博文b, 汲智越b, 谢明胜b, 渠桂荣a,b, 郭海明a,b   

  1. a. 河南师范大学环境学院 新乡 453007;
    b. 河南师范大学化学化工学院 新乡 453007
  • 收稿日期:2014-01-14 修回日期:2014-02-22 发布日期:2014-03-03
  • 通讯作者: 渠桂荣, 郭海明;
  • 基金资助:

    国家自然科学基金(Nos. 21072047,21172059,21272059,21202039和21372066)、河南省杰出青年基金(No. 114100510012)、河南省高校科技创新研究团队支持计划(No. 2012IRTSTHN006)、高等学校博士学科点专项科研基金(No. 20124104110006)资助项目.

A New Method for the Synthesis of Clofarabine

Xia Rana,b, Guo Zhenb, Qin Bowenb, Ji Zhiyueb, Xie Mingshengb, Qu Guironga,b, Guo Haiminga,b   

  1. a. School of Environment, Henan Normal University, Xinxiang 453007;
    b. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007
  • Received:2014-01-14 Revised:2014-02-22 Published:2014-03-03
  • Supported by:

    Foundation of Henan Scientific Committee (No. 114100510012), the Program for Innovative Research Team from the University of Henan Province (No. 2012IRTSTHN006), the Research Fund for the Doctoral Program of Higher Education (No. 20124104110006).

Clofarabine is the active ingredient in the anti-pediatric leukemia drug, which was approved by U.S. Food and Drug Administration in 2004. However, the previous reported methods have long steps, low yield and difficult separation of α/β anomers, which restrict the wide use of the drug. In this manuscript, the cheap and commercial available 2-chloroadenosine was chose as the starting material to synthesize the clofarabine. By using acetic acid and hydrazine, the selective deprotection of acetyl group in 2'-position was accomplished. Subsequently, the fluorination step was realized by diethylaminosulfurtrifluoride (DAST). The clofarabine was synthesized with 4 steps in 49% total yield as a pure β-anomer. Meanwhile, the strong steric hindrance of 2-substitution was favorable for the 2'-deacetylation. Notably, the clofarobine could be synthesized at a gram scale using this method, which showed the good future of industrial application.

Key words: clofarabine, 2-chloroadenosine, fluorination, synthesis, nucleoside