Synthesis of 2-substituted beta-cyclodextrin derivatives with a hydrolytic activity against the organophosphorylester paraoxon (original) (raw)
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European Journal of Medicinal Chemistry, 2005
b-Cyclodextrin was substituted by an iodosobenzoic acid derivative to create a catalytic hydrolytic activity against neurotoxic organophosphorus agents. The catalytic moiety was introduced on a secondary hydroxy group at the position 2 of a glucose unit. Several b-cyclodextrin derivatives were obtained. In these derivatives, the methylene linker occupied all potential positions on the aromatic ring. Kinetic assays were carried out with paraoxon as organophosphate model. Three regioisomers hydrolyzed paraoxon, although the paraoxon-leaving group, paranitrophenol, was not released from the b-cyclodextrin torus.
Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds
Beilstein Journal of Organic Chemistry, 2016
The aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target.
Beilstein Journal of Organic Chemistry, 2017
New derivatives of cyclodextrins were prepared in order to determine the relative importance of the structural key elements involved in the degradation of organophosphorus nerve agents. To avoid a competitive inclusion between the organophosphorus substrate and the iodosobenzoate group, responsible for its degradation, the latter group had to be covalently bound to the cyclodextrin scaffold. Although the presence of the α nucleophile iodosobenzoate was a determinant in the hydrolysis process, an imidazole group was added to get a synergistic effect towards the degradation of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative.
Regioselective access to 3I-O-substituted-β-cyclodextrin derivatives
Chem. Commun., 2009
Experimental procedures, 1 H and 13 C NMR data, identification of monosubstituted β-cyclodextrin regioisomers, NMR spectra for compounds 6a, 6b, 13a and 13b as specific and representative examples. I) Experimental procedures and NMR data : General: All solvents and reagents were purchased from commercial sources and used without further purification. Reactions were monitored by thin-layer chromatography (TLC) on a plate of silica gel 60 F 254 (E. Merck, Darmstadt, Germany) and detection by charring with sulfuric acid. Columns chromatography were performed on silica gel 60 (0.063-0.200 mm, E. Merck). LC-MS analyses were performed on a Waters 2695 Alliance coupled with a single quadripole mass spectrometer ZQ (Waters-Micromass, Manchester, UK) equipped with an electrospray ion source (ESI-MS). The composition of the mobile phase varied during the run according to a linear gradient as follows: A-B: 0 min (20:80, v/v), 0-50 min (50:50, v/v) at a flow rate of 1 mL/min. Compounds were loaded on a Alltech Carbohydrate ES 5u (5μm particle size, 250 mm x 4.6 mm) column using a sample injection volume of 20 µL (water solutions at 1 g/L for the compounds). The effluent was flow-split
Regioselective access to 3I-O-substituted-β-cyclodextrin derivatives
Chemical Communications, 2009
Experimental procedures, 1 H and 13 C NMR data, identification of monosubstituted β-cyclodextrin regioisomers, NMR spectra for compounds 6a, 6b, 13a and 13b as specific and representative examples. I) Experimental procedures and NMR data : General: All solvents and reagents were purchased from commercial sources and used without further purification. Reactions were monitored by thin-layer chromatography (TLC) on a plate of silica gel 60 F 254 (E. Merck, Darmstadt, Germany) and detection by charring with sulfuric acid. Columns chromatography were performed on silica gel 60 (0.063-0.200 mm, E. Merck). LC-MS analyses were performed on a Waters 2695 Alliance coupled with a single quadripole mass spectrometer ZQ (Waters-Micromass, Manchester, UK) equipped with an electrospray ion source (ESI-MS). The composition of the mobile phase varied during the run according to a linear gradient as follows: A-B: 0 min (20:80, v/v), 0-50 min (50:50, v/v) at a flow rate of 1 mL/min. Compounds were loaded on a Alltech Carbohydrate ES 5u (5μm particle size, 250 mm x 4.6 mm) column using a sample injection volume of 20 µL (water solutions at 1 g/L for the compounds). The effluent was flow-split
Synthesis of a β-cyclodextrin derivative bearing an azobenzene group on the secondary face
Tetrahedron Letters, 2008
An oxidative coupling Sonogashira-type reaction has been used to synthesize a b-cyclodextrin derivative bearing an azobenzene group on the secondary face for the first time starting from a b-cyclodextrin propargylated at one of its C-2 positions. The de-O-propargylation reaction and the formation of an oxidative homocoupling dimer were found to compete with the desired product under several Sonogashira-type reaction conditions. However, the use of a diluted reductive atmosphere of H 2 avoided the former and diminished the latter.
Pharmaceutical evaluation of hydroxyalkyl ethers of β-cyclodextrins
1988
ABSTRACT Hydroxyalkylated β-cyclodextrins (HA-β-CyDs), 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD), and hydroxyethyl-β-cyclodextrin (HE-β-CyD), were prepared and their physicochemical and biological properties and solubilizing abilities were studied and compared with those of parent β-cyclodextrin (β-CyD). HA-β-CyDs had much higher aqueous solubility ( > 50 w/v%) and were less hygroscopic than the parent β-CyD. Their surface activities were between those of β CyD and alkylated-β-cyclodextrins and were increased proportionately to their average degrees of substitution. The hemolytic activity (human erythrocytes) and local irritancy (rabbit muscle) of these compounds, and particularly of HE-β-CyD, were considerably less than those of natural cyclodextrin or dimethyl-β-cyclodextrin (DM-β-CyD). In contrast to surface activity, the hemolytic activity of HA-β-CyD decreased with the degree of substitution; possibly the difference in their ability to dissolve membrane components may be the reason. HA-β-CyDs were found to be powerful solubilizers of several drugs and no crystalline complexes were precipitated at high concentrations of solubilizer, a phenomenon which is often observed when β-CyD is used. HP-β-CyDs were somewhat better solubilizers than HE-β-CyDs and the preparations with the lower degrees of substitution were again better than those with the higher ones. The above data suggest that HA-β-CyDs are safer and more effective solubilizers for poorly water-soluble drugs than the parent cyclodextrin.
Synthesis of β-cyclodextrin derivatives functionalized with azobenzene
Tetrahedron, 2008
Two approaches for the synthesis of b-cyclodextrin and bis(b-cyclodextrin) bearing azobenzene on the primary face are reported. First, the nucleophilic substitution of mono-6-tosyl-b-cyclodextrin by azobenzene anion derivatives was reinvestigated and found to produce mono-3,6-anhydro-b-cyclodextrin as a side product. A slight modification of the reported reaction conditions including the use of Cs 2 CO 3 led to a substantial improvement of the yields. In addition, a convenient method based on the application of click chemistry led to 1,2,3-triazole-linked azobenzene-cyclodextrin derivatives in good yields.