title: Versatile synthesis and biological evaluation of novel 3'-fluorinated purine nucleosides.
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.
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China; Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Ren
authors.affiliation: Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
authors.forename: Haoyun
authors.initials: H
authors.lastname: An
authors.affiliation: Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hatala
authors.affiliation: Granlen, Inc., 7864 Paseo Tulipero, Carlsbad, CA 92009, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Stevens
authors.affiliation: College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Tao
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, Illinois 60637, USA.
authors.forename: Baicheng
authors.initials: B
authors.lastname: He
keywords: 3’-fluororibonucleoside; 6-substituted purine; anticancer; purine nucleoside; synthesis