Glycoclusters presenting lactose on calix[4]arene cores display trypanocidal activity (original) (raw)
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Synthesis of upper rim calix[4]arene divalent glycoclusters via amide bond conjugation
Tetrahedron, 2005
Synthetic routes for linking two sugar units at the upper rim of cone calix[4]arenes, through the formation of amide bonds, have been explored. Steric effects prevent the coupling of calix[4]arene dicarboxylic acid with simple aminoglycosides, whereas the corresponding reaction with carbohydrates bearing a two or three carbon atoms spacer, terminating with a primary amino group, allows the synthesis of several difunctionalized calix[4]arene neoglycoconjugates, attractive in chemical glycobiology and supramolecular chemistry. q
Organic & Biomolecular Chemistry, 2009
We present the first synthesis of calix[4]arene-based S-glycoclusters via photoinduced multiple thiol-ene coupling of tetra-and octa-allyl calix[4]arenes with peracetylated glucosyl thiol (67-88% yields). Moreover we describe the dual clustering at the upper and lower rim of a calix[4]arene with two different sugars (galactose and glucose) via sequential copper(I)-catalyzed azide-alkyne cycloaddition and photoinduced thiol-ene coupling. Ever since we reported in the mid-1990s on the first synthesis of calix[4]arene O-glycosides, 1 increasing interest has been focused by us 2 and others 3,4 on multiple glycosylation of calix[4]arene platforms to give glycoclusters. The final goal of those synthetic efforts was the preparation of structurally well-defined clusters to be used as probes in carbohydrate-lectin molecular recognition processes. Thus, in view of the fact that non-natural C-glycosides are impervious toward hydrolytic degradation, 5 subsequent research in our laboratory was carried out on the assembly of calix[4]arene-based C-glycoclusters. Accordingly, we first synthesized compounds in which the carbohydrate fragments were grafted to the macrocycle through a carbon chain formed by Wittig reaction of calix[4]arene aldehydes and sugar phosphoranes. 2c In a second instance we prepared C-glycoclusters via N-heterocycle ring formation, namely tetrazole from thermal azide-nitrile cycloaddition (ANC) 6 and triazole from Cu(I)-catalyzed azidealkyne cycloaddition (CuAAC). 7 Recently, we took advantage of the efficiency of the latter reaction, the quintessential click process, 8 for anchoring up to eight sialyl residues to calix[4]arene scaffolds in a one-pot process. 3 In this case S-sialoclusters were formed because all sialyl residues featured an anomeric thioether linkage. S-Linked glycoconjugates are known to display low susceptibility to enzymatic hydrolysis because the rate of hydrolysis of the thioglycosidic bond by glycohydrolases is several order of magnitudes slower than that of the corresponding O-glycosides. 9 The calix[4]arene-based S-sialoclusters proved to be active at submillimolar concentrations against BK (etiological agent of nephropathies) and influenza A viruses. Hence, giving the need to prepare calix[4]arene-based glycoclusters with robust tethers by the use of simple and efficient ligation reactions, we would like to report here on calixarene glycoclustering through sulfide bridges
Calix[8]arene-based glycoconjugates as multivalent carbohydrate-presenting systems
Tetrahedron Letters, 2003
An efficient approach for the introduction of eight mono-or disaccharide sugar moieties (D-glucose, N-acetyl-D-glucosamine, D-galactose, L-fucose, D-maltose and D-cellobiose) at the upper rim of calix[8]arene 1, using thioureido linkers, is reported. The obtained water-soluble, nanosized glycocalix[8]arenes 5b-10b may act as biomimetic carbohydrate systems and as hosts for highly polar organic molecules. Preliminary 1 H NMR complexation experiments of octaglycosyl derivative 7b and 10b with ionic guests are also reported.
Synthesis of carbohydrate functionalised n-propoxy-Calix[4]arenes
Tetrahedron Letters, 1998
The Suzuki ~action has been used to couple para-bromophenyl glycosides to boronic acid derivatives ofn-propox3,-Calix[41arenc ; " a one-pot " methodology eliminates the need to isolate the boronic acids and increases the overall yield. The synthesis provides a new class of carbohydrate containing calixarencs with a deepened cavi .ly. In order to enlarge the cavity of calix[4]arene derivatives, Atwood et allhave prepared a pphenylcalix[4]arene tetramethylether. Such calix[4]arene derivative should be capable of binding organic guest molecules. However the methyl derivatives are present in the semi-cone conformation, which is neither optimised for guest binding nor for increasing carbohydrate recognition by cooperative interaction. 2 In view of this, the tetra-propyl derivatives blocked in the cone conformation are of great interest. Bearing in mind the significant role played by sugars in many biological events, the coupling of carbohydrate antennae to the calix[4]arenes may provide a new class of molecular vectors. To this end, Dondoni and Ungaro3'4et al have described the synthesis of calix[4]arenes substituted by carbohydrate units at
Synthesis and Properties ofO-Glycosyl Calix[4]Arenes (Calixsugars)
Chemistry - A European Journal, 1997
Model 0-glycosylation reactions at either rim of calix arenes are described with the aim ofproviding access to 21 new family of carbohydrate-containing calixarene derivatives named calixsugars. One or two sugar moieties (u-mannofuranose and Li-glucopyranose) were introduced at the lower rim of the parent calix[4]arene by glycosylation of the phenolic hydroxyl groups by mcans of a Mitsunobu reaction. Tetrapropoxy calix[4]arcnes bearing two or four hydroxy-methyl groups at the upper rim wcre coupled with perbenzoylated thioethyl Dgalactoside and D-lactoside in thc presencc of the thiophilic promoter copper(i1) triflate. In this way /,'-linked bis-Keywords calixarenescarbohydrates * glycosylations host-guest chemistry * Mitsunobu reaction and tetrakis-0-galactosyl calix[4]arenes were obtained in good yield, the latter showing some solubility in water. For the 0-lactosyl derivatives only the bis-substituted compound could be obtained because of the competing formation of an intramolecular ether linkage between 1.3hydroxymethyl groups. Preliminary binding studies showed some affinity of the galactose-containing calixsugars toward charged carbohydrates and dihydrogen phosphate anion.
Molecules, 2020
The design and synthesis of a novel tert-butyl-calix[4]arene functionalized at 1, 3 positions of the lower rim with two terminal 2-hydroxybenzeledene-thiosemicarbazone moieties is reported. The new ligand with multi-dentate chelating properties was fully characterized by several techniques: ESI-Mass spectroscopy, FT-IR, 1H-NMR, and single crystal X-ray diffraction. The solid state structure confirms that the calix[4]arene macrocycle has the expected open cone conformation, with two opposite phenyl rings inclined outwards with large angles. The conformation of the two alkoxythiosemicarbazone arms produces a molecule with a C2 point group symmetry. An interesting chiral helicity is observed, with the two thiosemicarbazone groups oriented in opposite directions like a two-blade propeller. A water molecule is encapsulated in the center of the two-blade propeller through multiple H-bond coordinations. The antibacterial, antifungal, anticancer, and cytotoxic activities of the calix[4]arene-thiosemicarbazone ligand and its metal derivatives (Co2+, Ni2+, Cu2+, and Zn2+) were investigated. A considerable antibacterial activity (in particular against E. coli, MIC, and MBC = 31.25 µg/mL) was observed for the ligand and its metal derivatives. Significant antifungal activities against yeast (C. albicans) were also observed for the ligand (MIC = 31.25 µg/mL and MBC = 125 µg/mL) and for its Co 2+ derivative (MIC = 62.5 µg/mL). All compounds show cytotoxicity against the tested cancerous cells. For the Saos-2 cell line, the promising anticancer activity of ligand L (IC 50 < 25 µg/mL) is higher than its metal derivatives. The microscopic analysis of DAPI-stained cells shows that the treated cells change in morphology, with deformation and fragmentation of the nuclei. The hemo-compatibility study demonstrated that this class of compounds are suitable candidates for further in vivo investigations.
Synthesis of Novel Calixsugars: Calix[4]arene–Monosaccharide Conjugates Based on Amide Bonds
Tetrahedron, 2000
Novel calix[4]arenes containing two sugar moieties in the molecule have been prepared. Both components are connected through the amidic bonds on the lower rim of a calixarene unit preorganised in the cone conformation. This design leads to new chiral receptors with potential recognition ability towards suitable guest molecules. ᭧ Scheme 1. (a) NaN 3 , DMF-H 2 O, NH 2 CONH 2 , 120ЊC, two days; (b) PPh 3 , THF, rt.
Journal of the American Chemical Society, 2004
Self-assembly of molecular containers such as calixarene or resorcinarene derivatives has been widely studied in recent years to obtain interesting supramolecular structures. 1 The self-assembly process has been induced by hydrogen bonding, 2 ion pairing, 3 metal coordination, 4 and solvophobic forces. 5 Among the hydrogenbonded systems, particularly studied are the calixarene tetraurea derivatives, which give rise to the formation of dimeric selfassembled capsules able to complex, in a reversible fashion, neutral organic molecules and organic cations. It is well-known that amino acids and peptides are involved in the formation of several selfassembled structures such as R-helices,-sheets, and nanotubes. 6 However, they have never been used as promoters of selfassembling capsules from molecular cavities. 7 Only two examples are known in which amino acid derivatives have been used to adorn calix[4]arene tetraurea capsules to (i) increase their stability via peripheral hydrogen bonds 8 or (ii) transfer chiral information through noncovalent molecular assemblies. 9 Recently, we have been engaged in the study of N-and Clinked peptidocalix[4]arenes which have shown interesting supramolecular properties. 10 In this communication we report the first synthesis of a calixarene amino acid (5) and the unique self-assembly properties of the pseudopeptides in which this macrocyclic unit has been incorporated. To the best of our knowledge calix[4]arene amino acids, having an amino group on one aromatic nucleus and a carboxylic group on another, are unknown, since their synthesis is rather difficult. After several unsuccessful attempts, we finally synthesized compound 5 (Scheme 1), passing through derivative 3 11 which was
Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands
Beilstein Journal of Organic Chemistry, 2014
Four novel calix arene-based glycoclusters were synthesized by conjugating the saccharide units to the macrocyclic scaffold using the CuAAC reaction and using long and hydrophilic ethylene glycol spacers. Initially, two galactosylcalix[4]arenes were prepared starting from saccharide units and calixarene cores which differ in the relative dispositions of the alkyne and azido groups. Once the most convenient synthetic pathway was selected, two further lactosylcalix[4]arenes were obtained, one in the cone, the other one in the 1,3-alternate structure. Preliminary studies of the interactions of these novel glycocalixarenes with galectin-3 were carried out by using a lectin-functionalized chip and surface plasmon resonance. These studies indicate a higher affinity of lactosylover galactosylcalixarenes. Furthermore, we confirmed that in case of this specific lectin binding the presentation of lactose units on a cone calixarene is highly preferred with respect to its isomeric form in the 1,3-alternate structure.