A Convenient Route to Peracetylated 3-Deoxy-3-fluoro Analogues of d-Glucosamine and d-Galactosamine from a Černý Epoxide

Karban, Jindřich; Horník, Štěpán; Šťastná, Lucie Červenková; Sýkora, Ján

doi:10.1055/s-0033-1341187

Cited by 3 publications

(2 citation statements)

References 10 publications

(15 reference statements)

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“…Herein we also report on the cytotoxicity of prepared fluoro analogs in the human ovarian cancer A2780 and prostate cancer PC-3 cell lines. Preliminary results for the synthesis of compounds 5 and 6 were communicated earlier in a letter [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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

Horník¹,

Šťastná²,

Cuřínová³

et al. 2016

Beilstein J. Org. Chem.

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Summary 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.

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Section: Introductionmentioning

confidence: 99%

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

Horník¹,

Šťastná²,

Cuřínová³

et al. 2016

Beilstein J. Org. Chem.

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“…Although hydrophobic, it still generates a polar C–F bond that can undergo polar interactions with the protein, although typically of weaker strength. The substitution of F for OH has been widely studied, both in structural analyses of binding sites (to evaluate H-bond donor and acceptor requirements) and in the synthesis of therapeutic ligands [64,95,96,97,98].…”

Section: Replacement Of Oh Functional Groupsmentioning

confidence: 99%

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

Hevey

2019

Biomimetics

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The aberrant presentation of carbohydrates has been linked to a number of diseases, such as cancer metastasis and immune dysregulation. These altered glycan structures represent a target for novel therapies by modulating their associated interactions with neighboring cells and molecules. Although these interactions are highly specific, native carbohydrates are characterized by very low affinities and inherently poor pharmacokinetic properties. Glycomimetic compounds, which mimic the structure and function of native glycans, have been successful in producing molecules with improved pharmacokinetic (PK) and pharmacodynamic (PD) features. Several strategies have been developed for glycomimetic design such as ligand pre-organization or reducing polar surface area. A related approach to developing glycomimetics relies on the bioisosteric replacement of carbohydrate functional groups. These changes can offer improvements to both binding affinity (e.g., reduced desolvation costs, enhanced metal chelation) and pharmacokinetic parameters (e.g., improved oral bioavailability). Several examples of bioisosteric modifications to carbohydrates have been reported; this review aims to consolidate them and presents different possibilities for enhancing core interactions in glycomimetics.

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Five-Membered Ring Systems

Aitken¹,

Dragomir²

2015

Progress in Heterocyclic Chemistry

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A Convenient Route to Peracetylated 3-Deoxy-3-fluoro Analogues of d-Glucosamine and d-Galactosamine from a Černý Epoxide

Cited by 3 publications

References 10 publications

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

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

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

Five-Membered Ring Systems

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