title: Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine.
abstract: BACKGROUND
  Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein-carbohydrate interactions. This work is focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined.
  
  
  RESULTS
  Introduction of fluorine at C-3 was achieved by the reaction of 1,6-anhydro-2-azido-2-deoxy-4-O-benzyl-β-D-glucopyranose or its 4-fluoro analog with DAST. The retention of configuration in this reaction is discussed. Fluorine at C-4 was installed by the reaction of 1,6:2,3-dianhydro-β-D-talopyranose with DAST, or by fluoridolysis of 1,6:3,4-dianhydro-2-azido-β-D-galactopyranose with KHF2. The amino group was introduced and masked as an azide in the synthesis. The 1-O-deacetylated 3-fluoro and 4-fluoro analogs of acetylated D-galactosamine inhibited proliferation of the human prostate cancer cell line PC-3 more than cisplatin and 5-fluorouracil (IC50 28 ± 3 μM and 54 ± 5 μM, respectively).
  
  
  CONCLUSIONS
  A complete series of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine is now accessible by 1,6-anhydrohexopyranose chemistry. Intermediate fluorinated 1,6-anhydro-2-azido-hexopyranoses have potential as synthons in oligosaccharide assembly.
authors.affiliation: Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
authors.forename: Štěpán
authors.initials: Š
authors.lastname: Horník
authors.affiliation: Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Červenková Šťastná
authors.affiliation: Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Cuřínová
authors.affiliation: Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sýkora
authors.affiliation: Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Žlutý kopec 7, 656 53 Brno, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Káňová
authors.affiliation: Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Žlutý kopec 7, 656 53 Brno, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hrstka
authors.affiliation: Department of Inorganic Chemistry, Charles University, Hlavova 2030, 128 43 Praha 2, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Císařová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.affiliation: Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Karban
keywords: amino sugars; cytotoxicity; fluorinated carbohydrates; fluorine; hexosamines