The synthesis of mono- and difluorinated 2,3-dideoxy-d-glucopyranoses

Mtashobya, Lewis; Quiquempoix, Lucas; Linclau, Bruno

doi:10.1016/j.jfluchem.2014.08.023

Cited by 15 publications

(41 citation statements)

References 36 publications

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“…Then treatment of resulting compound 14 with Deoxo-Fluor™ furnished 2,3-dideoxy-difluoroglucose 15 with complete retention of configuration (2,3- trans relationship). 41 A TiCl 4 -mediated benzyl deprotection generated 16 containing the desired free hydroxyl group, which was further activated as triflate ( 17 ) and subjected to a nucleophilic fluorination using TBAF. Despite several attempts, 1,6-anhydro-2,3,4-trideoxy-2,3,4-trifluoro-β- d -galactopyranose 18 proved to be difficult to isolate due to its high volatility.…”

Section: Resultsmentioning

confidence: 99%

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

et al. 2018

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The replacement of hydroxyl groups by fluorine atoms on hexopyranose scaffolds may allow access to the discovery of new chemical entities possessing unique physical, chemical and ultimately even biological properties. The prospect of significant effects generated by such multiple and controlled substitutions encouraged us to develop diverse synthetic routes towards the stereoselective synthesis of polyfluorinated hexopyranoses, six of which are unprecedented. Hence, we report the synthesis of heavily fluorinated galactose, glucose, mannose, talose, allose, fucose, and galacturonic acid methyl ester using a Chiron approach from inexpensive levoglucosan. Structural analysis of single-crystal X-ray diffractions and NMR studies confirm the conservation of favored 4C1 conformation for fluorinated carbohydrate analogs, while a slightly distorted conformation due to repulsive 1,3-diaxial F···F interaction is observed for the trifluorinated talose derivative. Finally, the relative stereochemistry of multi-vicinal fluorine atoms has a strong effect on the lipophilicities (logP).

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Section: Resultsmentioning

confidence: 99%

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

et al. 2018

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“…The reaction of the D- gluco- configured 3-hydroxy derivatives 11 , and 26 with DAST, and the previously reported reactions of D- gluco -configured 3-hydroxy derivatives 33 [ 26 ], 34 [ 27 ], and 35 [ 25 ] ( Scheme 4 ) with DAST are an important means of obtaining 3-deoxy-3-fluoro derivatives of D- gluco -configured aldohexopyranoses which are difficult to prepare otherwise. These reactions characteristically proceed with a clean retention of configuration which can be explained by an anchimeric assistance of the trans -diaxially positioned (with respect to C3–OH) polar groups at C-2 or C-4, or by an internal fluorine attack as in S N i substitution.…”

Section: Resultsmentioning

confidence: 99%

“…The elaborated chemistry of 1,6-anhydrohexopyranose derivatives is suitable for this purpose [ 21 – 23 ]. Building on previous results from our [ 24 ] and other groups [ 25 – 28 ], we designed an approach based on stereoselective introduction of an azide as a masked amine group at C-2, and fluorine at C-3 and C-4 by nucleophilic displacement. Resulting 3-fluoro, 4-fluoro, and 3,4-difluoro analogs of 2-azido-1,6-anhydrohexopyranoses were then converted into the target fluoro analogs of D-glucosamine and D-galactosamine ( Scheme 1 ).…”

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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“…Levoglucosan derivatives 5 [ 16 ], 7 , and 8 [ 17 ] were obtained by hydrogenolysis using Pearlman’s catalyst of the known 10 [ 18 ], 12 [ 18 ], and 13 [ 17 , 18 ] in excellent yields while 6 [ 19 ] was obtained in a two steps sequence methylation-hydrogenolysis of the known 11 [ 20 ] ( Scheme 1 ). The known compounds 4 [ 12 , 21 ] and 9 [ 21 , 22 ] were obtained as described.…”

Section: Resultsmentioning

confidence: 99%

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives

et al. 2017

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Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine.

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The synthesis of mono- and difluorinated 2,3-dideoxy-d-glucopyranoses

Abstract: The synthesis of 2,3-dideoxy-2,3-difluoro-D-glucose and 2,3-dideoxy-3-fluoro-D-glucose is reported in respectively 5 and 6 steps from D-glucal, using a fluorination strategy.

Cited by 15 publications

References 36 publications

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

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

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives

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