Synthesis and in Vitro Cytotoxicity of Acetylated 3-Fluoro,4-Fluoro and 3,4-Difluoro Analogs of D-glucosamine and D-galactosamine.

0458825 - ÚCHP 2017 RIV DE eng J - Článek v odborném periodiku
Horník, Štěpán - Červenková Šťastná, Lucie - Cuřínová, Petra - Sýkora, Jan - Káňová, K. - Hrstka, R. - Císařová, I. - Dračínský, Martin - Karban, Jindřich
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. Roč. 12, Apr 20 (2016), s. 750-759. ISSN 1860-5397. E-ISSN 1860-5397
Grant CEP: GA ČR GA15-11223S
Institucionální podpora: RVO:67985858 ; RVO:61388963
Klíčová slova: amino sugars * cytotoxicity * fluorinated carbohydrates * fluorine * hexosamines
Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
Impakt faktor: 2.337, rok: 2016

This work deals with 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 in selected cancer cells is determined. 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 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).
Trvalý link: http://hdl.handle.net/11104/0259063