Stereospecific Access to 2,3,4-Trideoxy-2-3-4-Trifluoro-d-Glucose and d-Galactose Derivatives

Sarda, Pierre; Cabrera‐Escribano, Francisca; Alves, Ricardo José; Olesker, Alain; Lukacs, Gabor

doi:10.1080/07328308908047996

Cited by 14 publications

(27 citation statements)

References 6 publications

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“…14 ). 42 The last hurdle involved the C-6 fluorination and to that end, an O -aryl group was first installed to block the anomeric position. It is well documented that an electron-withdrawing polyfluoroalkyl group destabilizes adjacent carbocation center.…”

Section: Resultsmentioning

confidence: 99%

“…81 ) from the late acetylation of the intermediate 32 . 42 Standard deprotection under basic conditions furnished known glucose derivative 33 , initially prepared by the group of O’Hagan in 15 steps (0.4% global yield) from butynediol. 62 In comparison, the present strategy only required a 9-step sequence (only 6 purifications) from Cerny’s epoxide 13 with an overall 25% yield.…”

Section: Resultsmentioning

confidence: 99%

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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%

Section: Resultsmentioning

confidence: 99%

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

et al. 2018

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“…Isolation and purification of trifluoro-sugar 39 proved to be difficult due to its high volatility.C onsequently,t he crude mixture was subjected to acidic conditions (H 2 SO 4 ,A c 2 O), generating the acetolysis product 40 in 63 %y ield over three steps. [30] The configurations of the fluoro substituents were ascertained on the basis of 19 FNMR spectroscopy [ 19 FNMR (470 MHz): 3 J F2-H3 = 12.8 Hz, 3 J F3-F4 = 13.4 Hz, 3 J F3-H4 = 6.4 Hz, 3 J F4-H3 = 3 J F4-H5 = 27.0 Hz]. The aglycones were installed using the same strategy as described above, affording compounds 42 and 45 via bromide 41.I nb oth reactions, side product A was isolated from the mixture,o riginating from elimination of the anomeric bromo substituent (Scheme 5).…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

Denavit

Lainé

Bouzriba

et al. 2019

Chemistry A European J

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The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono‐ and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach. Given the scarcity of these compounds in the literature, in addition to their synthesis, their biological profiles were evaluated. Firstly, the fluorinated compounds were investigated as antiproliferative agents using normal human and mouse cells in comparison with cancerous cells. Most of the fluorinated compounds showed no antiproliferative activity. Secondly, these carbohydrate probes were used as potential inhibitors of galactophilic lectins. The first transverse relaxation‐optimized spectroscopy (TROSY) NMR experiments were performed on these interactions, examining chemical shift perturbations of the backbone resonances of LecA, a virulence factor from Pseudomonas aeruginosa. Moreover, taking advantage of the fluorine atom, the 19F NMR resonances of the monofluorogalactopyranosides were directly monitored in the presence and absence of LecA to assess ligand binding. Lastly, these results were corroborated with the binding potencies of the monofluorinated galactopyranoside derivatives by isothermal titration calorimetry experiments. Analogues with fluorine atoms at C‐3 and C‐4 showed weaker affinities with LecA as compared to those with the fluorine atom at C‐2 or C‐6. This research has focused on the chemical synthesis of “drug‐like” low‐molecular‐weight inhibitors that circumvent drawbacks typically associated with natural oligosaccharides.

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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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Stereospecific Access to 2,3,4-Trideoxy-2-3-4-Trifluoro-d-Glucose and d-Galactose Derivatives

Cited by 14 publications

References 6 publications

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives

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