Citation: XIA Ran, SUN Liping, QU Guirong, CHEN Leishan. Synthesis of Anti-leukemia Drug Cladribine[J]. Chinese Journal of Applied Chemistry, ;2016, 33(11): 1274-1278. doi: 10.11944/j.issn.1000-0518.2016.11.160027 shu

Synthesis of Anti-leukemia Drug Cladribine

XIA Ran ^a,, ,
SUN Liping ^b ,
QU Guirong ^c ,
CHEN Leishan ^a

1.
a College of Chemistry and Chemical Engineering;
2.
b School of Life Science and Technology, Xinxiang University, Xinxiang, He'nan 453003, China;
3.
c College of Chemistry and Chemical Engineering, He'nan Normal University, Xinxiang, He'nan 453007, China

Corresponding author: XIA Ran,
Received Date: 18 January 2016
Available Online: 5 May 2016
Fund Project:

Cladribine, an anti-leukemia drug, was synthesized in 43.5% total yield by 4 steps. Readily available 6-chloropurine was glycosylated with 1-chloro-3,5-di-O-p-benzoyl-D-ribose with good selectivity for β anomer in the presence of NaH. The C2-H of β-glycosylated product was converted into C2-NO₂ using 2,2,2-trifluoroacetic anhydride and tetrabutylammonium nitrate, followed by the transformation of C2-NO₂ into C2-Cl in NH₄Cl/EtOH solution. The deprotection step and ammonolysis of C6-Cl were accomplished in NH₃/CH₃OH. The separation of α-anomer, expensive starting materials and chromatography are not required. Moreover, cladribine could be produced on a 100 gram scale with maintained yield, indicating good potential in industrial applications.
- chloropurine,
- cladribine,
- nitration reaction,
- scalable synthesis
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