Synthesis of Protected 3-Deoxy-3-fluoro- and 4-Deoxy-4-fluoro-<scp>d</scp>-galactopyranosides from Levoglucosan

Lainé, Danny; Denavit, Vincent; Giguère, Denis

doi:10.1021/acs.joc.7b00543

Cited by 14 publications

(18 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first step transformed the 1,6-anhydroglucose into intermediate 34 on a multigram-scale via a described five-step protocol necessitating only one purification. 63 Reaction of 34 with KHF 2 directly furnished the desired 3-deoxy-3-fluoroglucopyranose 35 in a 65% yield. Subsequent fluorination of the C-2 position was achieved upon exposure to TBAF on triflate intermediate 36 .…”

Section: Resultsmentioning

confidence: 99%

“…6 Synthesis of 2,3,4-trideoxy-2,3,4-trifluoromannopyranose 44 and 2,3,4-trideoxy-2,3,4-trifluorotalopyranose 47 . Reagents and conditions: (a) ref 63 ; (b) KHF 2 (6.1 equiv), ethylene glycol, 200 °C, 5.0 h, 65%; (c) Tf 2 O (2.4 equiv), pyridine (9.6 equiv), CH 2 Cl 2 , 0 °C, 0.5 h; (d) 1 M TBAF in THF (10 equiv), THF, rt, 22 h, 85% over 2 steps; (e) TiCl 4 (2.0 equiv), CH 2 Cl 2 , 0 °C, 0.8 h, 88%; (f) TBANO 2 (3.0 equiv), CH 3 CN, microwave irradiation, 100 °C, 3 h, 91% over 2 steps; (g) Et 3 N·3HF (15 equiv), Et 3 N, 80 °C, 48 h; (h) Ac 2 O (200 equiv), H 2 SO 4 (80 equiv), 0 °C to rt, 16 h, then NaOAc (100 equiv), 0 °C to rt, 0.3 h, 71% over 3 steps, 9 / 10 = 1.5:1, α/β = 10:1; (i) 1 M NaOMe, MeOH, rt, 1 h, 94%; (j) p -bromobenzoylchloride (4.0 equiv), Et 3 N (8 equiv), DMAP (0.8 equiv), CH 2 Cl 2 , rt, 18 h, 83% for 44 , 80% for 47 ; (k) DAST (2.0 equiv), CH 2 Cl 2 , microwave irradiation, 100 °C, 1 h; (l) Ac 2 O (30 equiv), H 2 SO 4 (10 equiv), 0 °C to rt, 16 h, then NaOAc (20 equiv), 0 °C to rt, 0.3 h, 77% over 3 steps, α/β = 23:1; m) HCl (37% in water), water, rt, 1 h. Ac 2 O acetic anhydride, DAST diethylaminosulfur trifluoride, DMAP 4-(dimethylamino)pyridine, TBAF tetrabutylammonium fluoride, TBANO 2 tetrabutylammonium nitrite, Tf 2 O trifluoromethanesulfonic anhydride. ORTEP diagram of the molecular structure of 44 and 47 showing 50% thermal ellipsoid probability, carbon (gray), oxygen (red), fluorine (light green), hydrogen (white).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

et al. 2018

Self Cite

View full text Add to dashboard Cite

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).

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our next challenge was the preparation of 3‐deoxy‐3‐fluorogalactopyranoside derivatives, which was based on our previously described method and summarized in Scheme . Briefly, Cerny's epoxide 13 was treated with potassium hydrogen fluoride in ethylene glycol at 200 °C for 5 h to afford the desired 3‐deoxy‐3‐fluoroglucopyranose 14 in 65 % yield as the sole isomer.…”

Section: Resultsmentioning

confidence: 99%

“…The synthetic route was straightforward and commenced from 1,2:3,4‐di‐ O ‐isopropylidene‐α‐ d ‐galactopyranose 29 , an inexpensive starting material (Scheme ). Fluoro derivative 30 was isolated in 87 % yield by treatment with Me‐DAST under microwave irradiation (80 °C) for 1 h. This method provided a higher yield as compared to conventional heating . Isopropylidene hydrolysis was followed by acetyl protection, furnishing an anomeric mixture of 6‐deoxy‐6‐fluoro‐galactopyranose 31 .…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…It is therefore a good method for loading DOX by electrostatic interactions between anionic polymers and cationic drugs in the absence of organic solvents. However, introducing functional groups often makes the synthesis of anionic polymers complicated due to the process of protection and deprotection . Sardon's group reported the organocatalyzed synthesis of PEG‐based polyurethanes with carboxyl acid groups.…”

Section: Introductionmentioning

confidence: 99%

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Huang

Zhou

Yuan

et al. 2018

Polymer International

View full text Add to dashboard Cite

In order to obtain a pH-sensitive delivery carrier for doxorubicin (DOX), DOX-loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU-COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, 1 H NMR spectroscopy, gel permeation chromatography, UV-visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (−1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug-loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH-sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit-8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF-7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis-inducing effects on MCF-7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl-2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real-time polymerase chain reaction (PCR) assay and western blot assay.

show abstract

Synthesis of Protected 3-Deoxy-3-fluoro- and 4-Deoxy-4-fluoro-d-galactopyranosides from Levoglucosan

Cited by 14 publications

References 57 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

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

Contact Info

Product

Resources

About