Chinese Journal of Applied Chemistry ›› 2016, Vol. 33 ›› Issue (11): 1274-1278.DOI: 10.11944/j.issn.1000-0518.2016.11.160027

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Synthesis of Anti-leukemia Drug Cladribine

XIA Rana*(),SUN Lipingb,QU Guirongc,CHEN Leishana   

  1. aCollege of Chemistry and Chemical Engineering
    bSchool of Life Science and Technology,Xinxiang University,Xinxiang,He'nan 453003,China
    cCollege of Chemistry and Chemical Engineering,He'nan Normal University,Xinxiang,He'nan 453007,China
  • Received:2016-01-18 Accepted:2016-05-05 Online:2016-11-01 Published:2016-11-01
  • Contact: XIA Ran
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.21172059), the Key Scientific Research Projects in Universities of He'nan Province(No.16A150042)


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.

Key words: chloropurine, cladribine, nitration reaction, scalable synthesis