53784-82-0

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Chemical Properties

pale brown solid

Upstream product

• 10016-20-3 alpha cyclodextrin 

Relevant academic research and scientific papers

An improved and alternative method for the preparation of per(6-bromo-6-deoxy)cyclodextrins

A practical and efficient approach to the regioselective synthesis of per(6-bromo-6-deoxy)cyclodextrins is described. The method utilizes the easily accessible (chloro(phenylthio)methylene)dimethylammonium chloride (CPMA), circumventing disadvantages of earlier protocols. Georg Thieme Verlag Stuttgart. New York.

Synthesis of new series of α-cyclodextrin esters as dopamine carrier molecule

A new series of amphiphilic α-cyclodextrins were synthesized by grafting N-acylated amino acids [valine, leucine, phenylalanine, methionine, and tryptophan (3a-e)] to the primary hydroxyl groups via ester bond formation. The synthetic pathway involves sel

Mechanistic Understanding of a Robust and Scalable Synthesis of Per(6-deoxy-6-halo)cyclodextrins, Versatile Intermediates for Cyclodextrin Modification

Cyclodextrin (CD) perfunctionalization reactions are challenging to study because they proceed through a number of regioisomeric intermediates, thus warranting creative approaches to understanding the reaction mechanism. Particularly useful perfunctionalization targets are per(6-deoxy-6-halo)cyclodextrins. Their standard synthesis entails selective SN2 halogenation at their primary alcohols using a Vilsmeier reagent, but this requires a strongly basic quench to unmask the Vilsmeier-capped secondary alcohols. Herein we present an alternative and simple acidic hydrolytic quench that utilizes existing HX in the end-of-reaction solution and requires only the addition of water. We performed a detailed mechanistic investigation of the new quench, and a central feature was the use of proton sponge to develop an 1H NMR titration method for HX in organic solvent. This method was used to both quantify and remove HX in the prequenched reaction solution. The HX-free prequenched solution enabled us to (1) identify sensitive intermediates during the quench, (2) quantify all of the reaction byproducts, and (3) determine that HX is critical for hydrolysis. We then studied the halogenation reaction, wherein the new acidic quench facilitated high-throughput experimentation, using mass spectrometry as well as Design of Experiments with automated reaction profiling. Through this, we were able to establish robustness and understand the complex effects of Vilsmeier equivalents and temperature on the reaction outcome.

Precise Rate Control of Pseudorotaxane Dethreading by pH-Responsive Selectively Functionalized Cyclodextrins

A family of cyclodextrins functionalized with zero, one, two, or six amines was shown to control the rate of their threading and dethreading on a molecular axle depending on the pH and their substitution pattern. The originality of this system lies in the rate control of the switch by operating the stimulus directly on the macrocycle.

A convenient procedure for the formation of per(6-deoxy-6-halo) cyclodextrins using the combination of tetraethylammonium halide with [Et 2NSF2]BF4

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.

Novel polycarboxylated EDTA-type cyclodextrins as ligands for lanthanide binding: Study of their luminescence, relaxivity properties of Gd(iii) complexes, and PM3 theoretical calculations

Novel EDTA-type cyclodextrin (CD) derivatives, AEDTA, BEDTA and GEDTA, bearing 6, 7 and 8 bis(carboxymethyl)amino (iminodiacetic acid) groups, respectively, were prepared, and their complexation with Eu(iii), Tb(iii) and Gd(iii) ions was studied. Luminescence titrations and mass spectrometry showed formation of multimetal complexes (AEDTA 2 to 3, BEDTA mainly 3 and GEDTA exactly 4 metal ions), whereas luminescence lifetime measurements revealed the presence of exchangeable water molecules. Semiempirical quantum mechanical calculations, performed by the PM3 method and assessed by DFT calculations on model ligands, indicated efficient multi-metal complexation, in agreement with the experiment. The structures showed coordination of the metal ions in the outer primary side of the CDs via 4 carboxylate O atoms, 2 N atoms and a glucopyranose O atom per metal ion. Coordination of water molecules was also predicted, in accordance with experimental results. Calculated bond lengths and angles were in agreement with literature experimental values of lanthanide complexes. Calculated energies showed that complex stability decreases in the order GEDTA > BEDTA > AEDTA. 1H NMR molecular relaxivity measurements for the Gd(iii) complexes of AEDTA, BEDTA or GEDTA in water afforded values 4 to 10 times higher than the relaxivity of a commercial contrast agent at 12 MHz, and 6 to 20 times higher at 100 MHz. Solutions of BEDTA and GEDTA Gd(iii) complexes in human blood plasma displayed relaxivity values at 100 MHz 7 and 12 times, respectively, higher than the commercial agent. MTT tests of the Gd(iii) complexes using human skin fibroblasts did not show toxicity. Attempts to supramolecularly sensitize the luminescence of the lanthanide complexes using various aromatic CD guests were ineffective, evidently due to large guest-metal distances and inefficient inclusion. The described lanthanide complexes, could be useful as contrast agents in MRI.

Per(6-guanidino-6-deoxy)cyclodextrins: Synthesis, characterisation and binding behaviour toward selected small molecules and DNA

Per(6-guanidino-6-deoxy)-cyclodextrins 4a, 4b and 4c are novel derivatives, resulting from homogeneous introduction of the guanidino group at the primary side of α-, β- and γ-cyclodextrins. The products were obtained from the corresponding amino derivatives, as direct guanidinylation of the known bromo-cyclodextrins provided mixtures. The new compounds were fully characterized by NMR spectroscopy and other analytical methods, and their interaction with guest molecules was studied. Strong complexation with 4-nitrophenyl phosphate (NPP) disodium salt was observed (Kbinding ～5 × 104 M-1), whereas the non-phosphorylated substrate nitrobenzene (NB) formed a very weak complex. 2D ROESY spectra revealed cavity inclusion in both cases, however the orientation of NPP was opposite to that of NB, such that the phosphate group is oriented toward the primary side facing the guanidine groups. The strong affinity of 4 towards the phosphorylated guest suggested that interaction with DNA was possible. The new compounds were found to completely inhibit the migration of ultra pure calf thymus DNA during agarose gel electrophoresis, whereas no effects were observed with guanidine alone or with the plain cyclodextrins. Further, the condensation of DNA into nanoparticles in the presence of 4b was demonstrated by atomic force microscopy, confirming strong electrostatic interaction between the biopolymer and the multicationic products 4. The strong guanidine-phosphate interactions between 4 and DNA were therefore attributed to the clustering of the guanidine groups in the primary area of the cyclodextrin. Cavity effects could not be assessed. This journal is The Royal Society of Chemistry.

Bilayer vesicles of amphiphilic cyclodextrins: Host membranes that recognize guest molecules

A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of α-, β-, and γ-cyclodextrins (PEG = poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueous solution. The bilayer vesicles were characterized by transmission electron microscopy, dynamic light scattering, dye encapsulation, and capillary electrophoresis. The molecular packing of the amphiphilic cyclodextrins was investigated by using small-angle X-ray diffraction of bilayers deposited on glass and pressure-area isotherms obtained from Langmuir monolayers on the air-water interface. The bilayer thickness is dependent on the chain length, whereas the average molecular surface area scales with the cyclodextrin ring size. The alkyl chains of the cyclodextrins in the bilayer are deeply interdigitated. Molecular recognition of a hydrophobic anion (adamantane carboxylate) by the cyclodextrin vesicles was investigated by using capillary electrophoresis, thereby exploiting the increase in electrophoretic mobility that occurs when the hydrophobic anions bind to the nonionic cyclodextrin vesicles. It was found that in spite of the presence of oligo(ethylene glycol) substituents, the β-cyclodextrin vesicles retain their characteristic affinity for adamantane carboxylate (association constant Ka = 7.1 × 103M-1), whereas γ-cyclodextrin vesicles have less affinity (Ka = 3.2 × 103M-1), and α-cyclodextrin or non-cyclodextrin, nonionic vesicles have very little affinity (Ka ≈100M -1). Specific binding of the adamantane carboxylate to β-cyclodextrin vesicles was also evident in competition experiments with β-cyclodextrin in solution. Hence, the cyclodextrin vesicles can function as host bilayer membranes that recognize small guest molecules by specific non-covalent interaction.

An improved synthesis of 6-deoxyhalo cyclodextrins via halomethylenemorpholinium halides Vilsmeier-Haack Type reagents

Per(6-bromo-6-deoxy)cyclomalto-hexaose, -heptaose, and -octaose and the corresponding per(6-chloro-6-deoxy) derivatives were prepared in high yield by reaction of bromomethylenemorpholinium bromide or chloromethylenemorpholinium chloride, respectively, with cyclomaltohexaose, cyclomaltoheptaose and cyclomaltooctaose in dimethylformamide.

Synthesis of monofacially functionalized cyclodextrins bearing amino pendent groups

Derivatives of the cyclodextrins, αCD, βCD, and ΥCD, in which all primary hydroxyls are substituted by amine pendant groups, may be synthesized efficiently from the per-6-bromo-6-deoxy-CD derivatives by direct reaction with amines. These ACD derivatives, which bear six, seven, or eight amine pendent groups, represent interesting biomimetic receptors and catalysts. The synthetic strategy relies on quantitative transformation and efficient purification as is demonstrated by preparation of 11 homogeneous ACD derivatives. The limitations of the synthesis and potential adaptations are illustrated by the synthesis of several more ACD derivatives to >95% purity. A synthetic route to a CD persubstituted with primary amine functionalities at the primary face, per-6-bromo-6-deoxy-CD, yields an alternative reagent to the simple per-6-bromo-6-deoxy-CD, which is more suitable for further synthetic transformations. The synthetic strategy is further adapted to preparation of a prototypical (6 + 1)-ACD derivative in which one primary position is substituted with a sulfide group and the remaining six primary face positions are substituted with amine pendent groups.