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Horník Š, Červenková Šťastná L, Cuřínová P, et al. Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine. Beilstein J Org Chem. 2016;12:750-9doi: 10.3762/bjoc.12.75.
Horník, �. �., Červenková Šťastná, L., Cuřínová, P., Sýkora, J., Káňová, K., Hrstka, R., Císařová, I., Dračínský, M., & Karban, J. (2016). Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine. Beilstein journal of organic chemistry, 12750-9. https://doi.org/10.3762/bjoc.12.75
Horník, Štěpán, et al. "Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine." Beilstein journal of organic chemistry vol. 12 (2016): 750-9. doi: https://doi.org/10.3762/bjoc.12.75
Horník Š, Červenková Šťastná L, Cuřínová P, Sýkora J, Káňová K, Hrstka R, Císařová I, Dračínský M, Karban J. Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine. Beilstein J Org Chem. 2016 Apr 20;12:750-9. doi: 10.3762/bjoc.12.75. eCollection 2016. PMID: 27340467; PMCID: PMC4901990.
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Beilstein J Org Chem. 2016 Apr 20;12:750-9. doi: 10.3762/bjoc.12.75. eCollection 2016.

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine.

Beilstein journal of organic chemistry

Štěpán Horník, Lucie Červenková Šťastná, Petra Cuřínová, Jan Sýkora, Kateřina Káňová, Roman Hrstka, Ivana Císařová, Martin Dračínský, Jindřich Karban

Affiliations

  1. Institute of Chemical Process Fundamentals of the CAS, Rozvojová 135, 165 02 Praha, Czech Republic.
  2. Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Žlutý kopec 7, 656 53 Brno, Czech Republic.
  3. Department of Inorganic Chemistry, Charles University, Hlavova 2030, 128 43 Praha 2, Czech Republic.
  4. Institute of Organic Chemistry and Biochemistry, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.

PMID: 27340467 PMCID: PMC4901990 DOI: 10.3762/bjoc.12.75

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).

CONCLUSION: 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.

Keywords: amino sugars; cytotoxicity; fluorinated carbohydrates; fluorine; hexosamines

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