A New Method for the Synthesis of Clofarabine

作者：Xia Ran^*; Guo Zhen; Qin Bowen; Ji Zhiyue; Xie Mingsheng; Qu Guirong; Guo Haiming

来源：Chinese Journal of Organic Chemistry, 2014, 34(6): 1154-1160.

DOI：10.6023/cjoc201401024

• clofarabine
• 2-chloroadenosine
• fluorination
• synthesis
• nucleoside

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 alpha/beta 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 beta-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.

• 出版日期2014-6
• 单位河南师范大学