A New Method for the Synthesis of Clofarabine

doi:10.6023/cjoc201401024

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

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一种新的合成氯法拉滨的方法

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

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 E-mail:quguir@sina.com;guohm518@hotmail.com
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 Ran^a,b, Guo Zhen^b, Qin Bowen^b, Ji Zhiyue^b, Xie Mingsheng^b, Qu Guirong^a,b, Guo Haiming^a,b

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).

1. A New Method for the Synthesis of Clofarabine.PDF(851KB)

Abstract

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

Cite this article

Xia Ran, Guo Zhen, Qin Bowen, Ji Zhiyue, Xie Mingsheng, Qu Guirong, Guo Haiming. A New Method for the Synthesis of Clofarabine[J]. Chin. J. Org. Chem., 2014, 34(6): 1154-1160.

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一种新的合成氯法拉滨的方法

A New Method for the Synthesis of Clofarabine

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