Versatile synthesis and biological evaluation of novel 3'-fluorinated purine nucleosides

  • Beilstein J Org Chem. 2015 Dec 9:11:2509-20. doi: 10.3762/bjoc.11.272.
Hang Ren  1 ,  Haoyun An  2 ,  Paul J Hatala  2 ,  William C Stevens Jr  2 ,  Jingchao Tao  3 ,  Baicheng He  4
Affiliations
  • 1. College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China; Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
  • 2. Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
  • 3. College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China.
  • 4. Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, Illinois 60637, USA.
PMID: 26734098 DOI: 10.3762/bjoc.11.272
Abstract

A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3'-fluorinated analogues were constructed from a common 3'-deoxy-3'-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3'-fluororibose purine nucleosides 1-15 and eight 3'-fluororibose 2-chloro/2-aminopurine nucleosides 16-23 with various substituents at position 6 of the purine ring were efficiently synthesized. Furthermore, 3'-fluorine analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon Cancer) and 143B (osteosarcoma Cancer) tumor cell lines. We have demonstrated 3'-fluorine purine nucleoside analogues display potent tumor cell growth inhibition activity at sub- or low micromolar concentration.

Keywords
3’-fluororibonucleoside; 6-substituted purine; anticancer; purine nucleoside; synthesis.
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