- Solubilization of polycyclic aromatics in water by γ-cyclodextrin derivatives
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A series of hydrophilic per-6-thio-6-deoxy-γ-cyclodextrins (CDs) were synthesized from per-6-iodo-6-deoxy-γ-CD. These new hosts are able to solubilize polycyclic aromatic guests in aqueous solution to much higher extents than native CDs. Phase-solubility diagrams were mostly linear in accordance with both 1:1 and 1:2 CD-guest complexes in aqueous solution. The stoichiometry of the inclusion complexes was further investigated by fluorescence spectroscopy, which revealed very pronounced Stokes shifts typical for 1:2 complexes. This finding was further consolidated by quantum mechanical calculations of dimer formation of the guests and space-filling considerations by using the cross-sectional areas of the CDs and guests. The calculated dimerization energies correlated well with the binding free energies measured for the 1:2 complexes, and provided the main contribution to the driving force of complexation in the γ-CD cavity. Copyright
- Wang, Hai Ming,Wenz, Gerhard
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- Facial Synthesis and Bioevaluation of Well‐Defined OEGylated Betulinic Acid‐Cyclodextrin Conjugates for Inhibition of Influenza Infection
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Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti‐HIV‐1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa‐, hepta‐ and octavalent BA derivatives based on α-, β-and γ-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave‐assisted copper‐catalyzed 1,3‐di-polar cycloaddition reaction. The generated BA‐cyclodextrin conjugates were tested for their in vitro activity against influenza A/WSN/33 (H1N1) virus and cytotoxicity. Among the tested com-pounds, 58, 80 and 82 showed slight cytotoxicity to Madin‐Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 μM. Four conjugates 51 and 69–71 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration val-ues of 5.20, 9.82, 7.48 and 7.59 μM, respectively. The structure‐activity relationships of multivalent BA‐cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.
- Chen, Yingying,Gao, Qianqian,Liang, Shuobin,Ma, Xinyuan,Tretyakova, Elena V.,Wang, Xinchen,Xiao, Sulong,Zhang, Yongmin,Zhou, Demin
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- Method for synthesizing beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in water phase
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The invention discloses a method for synthesizing a beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in a water phase. The method comprises the following steps: in the water phase, catalyzing ketone and aldehyde with equal molar weig
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Paragraph 0037-0038
(2021/01/28)
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- The uncommon strong inhibition of α-glucosidase by multivalent glycoclusters based on cyclodextrin scaffolds
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The homeostasis disruption of d-glucose causes diabetes, a dramatic chronic disease worldwide. Type 1 diabetes is a successfully treatable form, where blood d-glucose is regulated by insulin treatment. In contrast type 2 diabetes, the non-insulin dependent kind, is problematic. The control of the d-glucose blood level via intestinal α-d-glucosidase inactivation can be achieved by using competitive inhibitors, such as iminosugars (e.g. acarbose) or sulfonium sugar derivatives (e.g. salacinol). Recently, an unprecedented result showed that multivalent diamond nanoparticles grafted with unmodified sugars displayed α-glucosidase inhibition at low micromolar concentrations. Herein we describe the synthesis of multivalent glycoclusters using cyclodextrins (CDs) as scaffolds and an assessment of their role as inhibitors of α-d-glucosidase. The glycoclusters were efficiently obtained from per-azido α, β and γ-CD derivatives and propargyl glycosides using click-chemistry under microwave irradiation. The methodology was successfully applied to various protected and non-protected propargylated monosaccharides, including both O- and S-glycosides, giving clear evidence of its versatility. The targeted 6-per-glycosylated CDs were isolated in moderate to excellent yields (30-90%) by silica gel chromatography. The results showed inhibition of α-glucosidase from Saccharomyces cerevisiae with IC50 values in the 32-132 μM range, lower than that of acarbose (IC50 = ～250 μM), a well-known competitive inhibitor used in the clinical treatment of type 2 diabetes. Preliminary experiments suggest a mixed-type non-competitive inhibition mode for these new glycoclusters.
- Alali, Urjwan,Vallin, Aurélie,Bil, Abed,Khanchouche, Takwa,Mathiron, David,Przybylski, Cédric,Beaulieu, Rémi,Kovensky, José,Benazza, Mohammed,Bonnet, Véronique
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p. 7228 - 7237
(2019/08/07)
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- β-Cyclodextrin Covalent Organic Framework for Selective Molecular Adsorption
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Covalent organic frameworks (COF) are complex functional systems constructed with atomic precision by linking well-defined building blocks through robust covalent bonds. β-cyclodextrin (β-CD) is a most employed supramolecule which bears a hydrophobic cavity guiding molecular specific recognitions. Building COF with asymmetric β-CD linkers is challenging and has never been reported. Here, β-CD COF is grown with heptakis(6-amino-6-deoxy)-β-CD and terephthalaldehyde in green solvents of water and ethanol at room temperature. The COF is characterized by powder X-ray diffraction, which matches well with the simulated crystal structure. Weaving β-CD into a framework through reticular chemistry allows the integration of a large amount of β-CD units (50 mol %), much higher than β-CD polymers. The β-CD COF has larger surface area, more uniform pore size, and higher thermal stability than the non-crystalline β-CD polymer produced by the same reagents. Finally, the β-CD COF holds abundant specific interaction sites enabling selective molecular adsorption.
- Wang, Ren-Qi,Wei, Xue-Bing,Feng, Yu-Qi
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supporting information
p. 10979 - 10983
(2018/07/31)
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- Mechanochemical Preparation of Stable Sub-100 nm γ-Cyclodextrin:Buckminsterfullerene (C60) Nanoparticles by Electrostatic or Steric Stabilization
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Buckminster fullerene (C60)′s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C60 is by comple
- Van Guyse, Joachim F. R.,de la Rosa, Victor R.,Hoogenboom, Richard
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p. 2758 - 2766
(2018/02/06)
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- Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates
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Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4.7?μM. The time-of-addition assay indicated that compound 28 inhibited the entry of influenza virus into host cell. Further hemagglutination inhibition (HI) and surface plasmon resonance (SPR) assays indicated that compound 28 tightly bound to influenza HA protein with a dissociation constant (KD) of 4.0?μM. Our results demonstrated a strategy of using per-O-methylated β-CD as a scaffold for designing multivalent compounds to disrupt influenza HA protein-host receptor protein interaction and thus block influenza virus entry into host cells.
- Tian, Zhenyu,Si, Longlong,Meng, Kun,Zhou, Xiaoshu,Zhang, Yongmin,Zhou, Demin,Xiao, Sulong
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p. 133 - 139
(2017/04/14)
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- Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins
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A number of per-6-substituted cyclodextrin derivative syntheses have been effectively carried out in a planetary ball mill under solvent-free conditions. The preparation of Bridion and important per-6-amino/thiocyclodextrin intermediates without polar aprotic solvents, a source of byproducts and persistent impurities, could be performed. Isolation and purification processes could also be simplified. Considerably lower alkylthiol/halide ratio were necessary to reach the complete reaction in comparison with thiourea or azide reactions. While the presented mechanochemical syntheses were carried out on the millimolar scale, they are easily scalable.
- Jicsinszky, Laszlo,Caporaso, Marina,Martina, Katia,Gaudino, Emanuela Calcio,Cravotto, Giancarlo
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supporting information
p. 2364 - 2371
(2016/12/07)
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- Pyridyl-cyclodextrin for ultra-hydrosolubilization of [60]fullerene
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An efficient hydrosolubilizing reagent for [60]fullerene (C60) was newly developed with a γ-cyclodextrin (γ-CD) derivative having triazole-methoxypyridyl moieties at its 6-hydroxyl positions (PCD). Through solid-state mechanochemical complexation, PCD forms a hydrosoluble inclusion complex of C60 with a concentration of more than 70 mM. This is approximately 90 times greater than that with non-substituted γ-CD prepared by the same method. This journal is the Partner Organisations 2014.
- Nobusawa, Kazuyuki,Payra, Debabrata,Naito, Masanobu
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supporting information
p. 8339 - 8342
(2014/07/22)
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- A convenient procedure for the formation of per(6-deoxy-6-halo) cyclodextrins using the combination of tetraethylammonium halide with [Et 2NSF2]BF4
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A convenient and efficient procedure for the regioselective halogenation of the primary alcohols of cyclodextrins using the reagent combination of tetraethylammonium halide with [Et2NSF2]BF4 is described. Georg Thieme Verlag Stuttgart New York.
- Liu, Xiaofeng,Cheng, Sen,Wang, Xiaolei,Xue, Weihua
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p. 3103 - 3105
(2013/12/04)
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- 6-Mercapto-cyclodextrin derivatives:reversal agents for drug-induced neuromuscular block
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Disclosed is a 6-mercapto-cyclodextrin derivative having general formula (I) wherein m is 0-7 and n is 1-8 and m+n=7 or 8; R is (C1-6)alkylene, optionally substituated with 1-3 OH groups, or (CH2)o-phenylene-(CH2)p—; o and p are independently 0-4; X is COOH, CONHR1, NHCOR2, SO2OH, PO(OH)2, O(CH2—CH2—O)q—H, OH or tetrazol-5-yl; R1is H or (C1-3)alkyl; R2is carboxyphenyl; q is 1-3; or pharmaceutically acceptable salts thereof. The 6-mercaptocyclodextrin derivative is highly suitable for use in the reversal of drug-induced neuromuscular block.
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Page column 8-9
(2010/02/06)
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- Isothiocyanates and cyclic thiocarbamates of α,α'-trehalose, sucrose, and cyclomaltooligosaccharides
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6,6'-dideoxy-6,6'-diisothiocyanato-α,α'-trehalose (4), 6-deoxy-6-isothiocyanato-α-D-fructofuranose β-D-fructopyranose 1,2':2,1'-dianhydride (11), 6,6'-dideoxy-6,6'-diisothiocyanatosucrose (16), and per(6-deoxy-6-isothiocyanato)-cyclomaltohexaose (23), -cyclomaltoheptaose (27), and -cyclomaltooctaose (31) have been prepared in high yield by reaction of the corresponding amino sugars with thiophosgene.In the absence of base, all isothiocyanates were stable and could be stored and acetylated without decomposition.In the presence of trietylamine, 6,6'-dideoxy-6,6'-diisothiocyanato-α,α'-trehalose underwent intramolecular cyclisation involving HO-4 to give the corresponding bis(cyclic thiocarbamate).The product of cyclisation at a single glucopyranosyl unit was obtained in the treatment of the above diisothiocyanate with mixed (H+, HO-) ion-exchange resin.Under identical reaction conditions, 6,6'-dideoxy-6,6'-diisothiocyanatosucrose yielded exclusively the product of intramolecular cyclisation at the D-glucopyranosyl moiety, while derivatives of α-D-fructofuranose β-D-fructopyranose 1,2':2,1'-dianhydride and cyclomaltooligosaccharides remained unchanged. Keywords: Sugar isothiocyanates; Trehalose; Difructose dianhydrides; Sucrose; Cyclomaltooligosaccharides
- Fernandez, Jose Manuel Garcia,Mellet, Carmen Ortiz,Blanco, Jose Luis Jimenez,Mota, Jose Fuentes,Gadelle, Andree,et al.
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