Stereoisomer separation of flavanones and flavanone‐7‐O‐glycosides by means of nanoliquid chromatography employing derivatized β‐cyclodextrins as mobile‐phase additive

A nanoliquid chromatographic method for the stereoisomer separation of some flavanone aglycones and 7‐O‐glycosides has been proposed employing a C18 capillary column and a chiral mobile‐phase additive such as cyclodextrin. The chiral separation of eriodictyol, naringenin, and hesperitin was obtained by addition of carboxymethyl‐β‐cyclodextrin to the mobile phase, whereas eriocitrin, naringin, narirutin, and hesperidin diastereoisomers were resolved by using sulfobutyl ether‐β‐cyclodextrin. The influence of the composition of the mobile phase, the length of the capillary column, and the flow rate on the chiral recognition were investigated. At optimum conditions, baseline separation for the selected aglycones and glycosylated forms were achieved with a mobile phase consisting of 50 mM sodium acetate buffer pH 3 and 30% methanol containing 20 mM of carboxymethyl‐β‐cyclodextrin and 10 mM of sulfobutyl ether‐β‐cyclodextrin, respectively. Precision, linearity, and sensitivity of the method were tested. Limits of detection and quantification for the studied flavanone glycosides were in the range 1.3‐2.5 and 7.5‐12.5 µg/mL, respectively. The method was used for the determination of the diastereomeric composition of the flavanone‐7‐O‐glycosides in Citrus juices after solid‐phase extraction procedure.     

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d‐maltosyl‐β‐cyclodextrin

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin were synthesized using functionalized silica as a matrix, 4‐(phenyldiazenyl)phenol as a light‐sensitive monomer, and 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin as a template. Fourier transform infrared spectroscopy results indicated that 4‐(phenyldiazenyl)phenol was grafted onto the surface of functionalized silica. The obtained imprinted polymers exhibited specific recognition toward 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin. Equilibrium binding experiments showed that the photoirradiation surface molecularly imprinted polymers obtained the maximum adsorption amount of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin at 20.5 mg/g. In binding kinetic experiments, the adsorption reached saturation within 2 h with binding capacity of 72.8%. The experimental results showed that the adsorption capacity and selectivity of imprinted polymers were effective for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin, indicating that imprinted polymers could be used to isolate 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin from a conversion mixture containing β‐cyclodextrin and maltose. The results showed that the imprinted polymers prepared by this method were very promising for the selective separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin.     

2-萘-(OCH2CH2)n-金刚胺与6-单取代环糊精衍生物的光诱导电子转移反应

A number of naphthalene donor compounds that possess an adamantanamine binding moiety and an (OCH2CH2)n (nn1, 2, 3, 4, 6, 8) spacer were synthesized. The fluorescence quenching between these donor substrates and mono-6-O-p-nitrobenzoyl-β-cyclodextrin (pNBCD) and mono-6-O-m-nitrobenzoyl-β-cyclodextrin(mNBCD) was studied in detail. It was found that very efficient fluorescence quenching could occur in these supramolecular systems. This quenching was attributed to the photoinduced electron transfer inside the supramolecular assembly between the naphthalene donors and cyclodextrin acceptors. Detailed Stern-Volmer constants were measured and they were partitioned into dynamic Stern-Volmer quenching constants and static binding constants. It was demonstrated that the binding constants between all the naphthalene compounds and cyclodextrins are the same as they possess the same binding site, i.e., adamantanamine.     

Intramolecular Oxidative O‐Demethylation of an Oxoferryl Porphyrin Complexed with a Per‐O‐methylated β‐Cyclodextrin Dimer

The intramolecular oxidation of ROCH₃ to ROCH₂OH, where the latter compound spontaneously decomposed to ROH and HCHO, was observed during the reaction of the supramolecular complex (met‐hemoCD3) with cumene hydroperoxide in aqueous solution. Met‐hemoCD3 is composed of meso‐tetrakis(4‐sulfonatophenyl)porphinatoiron(III) (Fe^IIITPPS) and a per‐O‐methylated β‐cyclodextrin dimer having an ‐OCH₂PyCH₂O‐ linker (Py=pyridine‐3,5‐diyl). The O=Fe^IVTPPS complex was formed by the reaction of met‐hemoCD3 with cumene hydroperoxide, and isolated by gel‐filtration chromatography. Although the isolated O=Fe^IVTPPS complex in the cyclodextrin cage was stable in aqueous solution at 25 °C, it was gradually converted to Fe^IITPPS (t_1/2=7.6 h). This conversion was accompanied by oxidative O‐demethylation of an OCH₃ group in the cyclodextrin dimer. The results indicated that hydrogen abstraction by O=Fe^IVTPPS from ROCH₃ yields HO‐Fe^IIITPPS and ROCH₂^.. This was followed by radical coupling to afford Fe^IITPPS and ROCH₂OH. The hemiacetal (ROCH₂OH) immediately decomposed to ROH and HCHO. This study revealed the ability of oxoferryl porphyrin to induce two‐electron oxidation.     

Synthesis of the chiral selector heptakis(6‐O‐methyl)‐β‐cyclodextrin by phase‐transfer catalysis and hydrazine‐mediated transfer‐hydrogenation

The exhaustive primary‐side alkylation of cyclodextrins has never been achieved directly. The undesired and simultaneous derivatization of the secondary hydroxyl moieties generates intricate isomeric mixtures that are challenging to purify, analyse and characterize. The aim of this study was to develop a chromatography‐free and up‐scalable strategy towards the preparation of per‐6‐O‐methylated cyclodextrin and to test the compound as potential chiral selector. The target molecule was prepared according to a five‐step synthesis by using methyltriphenylphosphonium bromide as catalyst under heterogeneous conditions. The removal of benzyl moieties, used as temporary secondary‐side protecting groups, was attained by applying hydrazine‐carbonate in the presence of Pd/C. All the intermediates were obtained in high yields, thoroughly characterized and their purity was assessed by ad‐hoc developed HPLC methods. The per‐6‐O‐methylated β‐cyclodextrin showed promising chiral recognition ability as background electrolyte additive in cyclodextrin‐modified capillary electrophoresis using the recreational drug methylene‐dioxypyrovalerone as model compound. Additionally, a model for the inclusion geometry between the single isomer host and the selected drug was developed based on the extensive 2D NMR analysis. The versatility of the proposed synthetic strategy opens the way to the industrial production of homogeneously primary‐alkylated cyclodextrins and to their wide application in chiral separation of various drugs.     

Synergetic mechanism and enantioseparation of aromatic β‐amino acids by biphasic chiral high‐speed counter‐current chromatography

A biphasic chiral recognition system based on chiral ligand exchange with Cu(II)‐N‐n‐dodecyl‐L‐proline and hydroxypropyl‐β‐cyclodextrin as an additive was developed to enantioseparate aromatic β‐amino acids by high‐speed counter‐current chromatography. The biphasic chiral recognition system was established with an n‐butanol/water (1:1, v/v) solvent system by adding N‐n‐dodecyl‐L‐proline and Cu(II) ions to the organic phase and hydroxypropyl‐β‐cyclodextrin to the aqueous phase. Several separation parameters, such as temperature, pH value, and chiral selector concentration, were systematically investigated by enantioselective liquid–liquid extraction. Under the optimal separation conditions, 54.5 mg of (R,S)‐β‐phenylalanine and 74.3 mg of (R,S)‐β‐3,4‐dimethoxyphenylalanine were baseline enantioseparated. More importantly, the synergistic enantiorecognition mechanism, based on the Cu(II)‐N‐n‐dodecyl‐L‐proline and hydroxypropyl‐β‐cyclodextrin, was discussed for the first time.     

The influence of the substituent position in monocarboxymethyl‐γ‐cyclodextrins on enantioselectivity in capillary electrophoresis

Three newly synthesized chiral selectors, namely, 2^I‐O‐, 3^I‐O‐, and 6^I‐O‐carboxymethyl‐γ‐cyclodextrin, native γ‐cyclodextrin, and commercially available carboxymethylated γ‐cyclodextrin with degree of substitution of 3–6 were used as additives in a background electrolyte composed of phosphate buffer at 20 mmol/L concentration and pH 2.5. This system was used for the analysis of several biologically significant low‐molecular‐mass chiral compounds by capillary electrophoresis. The results confirmed that the position of carboxymethyl group influences the enantioseparation efficiency of all the studied analytes. The 2^I‐O‐ and 3^I‐O‐ regioisomers provide a significantly better resolution than native γ‐cyclodextrin, while the 6^I‐O‐regioisomer gives only a slightly better enantioseparation than native γ‐cyclodextrin. The application of γ‐cyclodextrin possessing higher number of carboxymethyl groups led to the best resolution for the majority of the compounds analyzed.     

Preparative enantioseparation of loxoprofen precursor by recycling countercurrent chromatography with hydroxypropyl‐β‐cyclodextrin as a chiral selector

Recycling countercurrent chromatography was successfully applied to the resolution of 2‐(4‐bromomethylphenyl)propionic acid, a key synthetic intermediate for synthesis of nonsteroidal anti‐inflammatory drug loxoprofen, using hydroxypropyl‐β‐cyclodextrin as chiral selector. The two‐phase solvent system composed of n‐hexane/n‐butyl acetate/0.1 mol/L citrate buffer solution with pH 2.4 (8:2:10, v/v/v) was selected. Influence factors for the enantioseparation were optimized, including type of substituted β‐cyclodextrin, concentration of hydroxypropyl‐β‐cyclodextrin, separation temperature, and pH of aqueous phase. Under optimized separation conditions, 50 mg of 2‐(4‐bromomethylphenyl)propionic acid was enantioseparated using preparative recycling countercurrent chromatography. Technical details for recycling elution mode were discussed. The purities of both the S and R enantiomers were over 99.0% as determined by high‐performance liquid chromatography. The enantiomeric excess of the S and R enantiomers reached 98.0%. The recovery of the enantiomers from eluted fractions was 40.8–65.6%, yielding 16.4 mg of the S enantiomer and 10.2 mg of the R enantiomer. At the same time, we attempted to enantioseparate the anti‐inflammatory drug loxoprofen by countercurrent chromatography and high‐performance liquid chromatography using a chiral mobile phase additive. However, no successful enantioseparation was achieved so far.     

A new single‐urea‐bound 3,5‐dimethylphenylcarbamoylated β‐cyclodextrin chiral stationary phase and its enhanced separation performance in normal‐phase liquid chromatography

A new single‐urea‐bound chiral stationary phase based on 3,5‐dimethylphenylcarbamoylated β‐cyclodextrin was prepared through the Staudinger reaction of mono (6^A‐azido‐6^A‐deoxy)‐per(3,5‐dimethylphenylcarbamoylated) β‐cyclodextrin and 3‐aminopropyl silica gel under CO₂ atmosphere. The new phase exhibited good enantioseparation performance for 33 analytes using normal‐phase HPLC conditions; 19 of them were baseline separated. Effects of structure of analytes, alcoholic modifiers, and acidic/basic additives on separation performances of this new cyclodextrin chiral stationary phase have been studied in detail. The results showed that the retention and resolution of acidic and basic analytes on the CSP were greatly affected by the additives. Peak symmetry for some analytes could be improved by simultaneously adding acidic and basic additives to the mobile phase. This work expands the potential applications of the cyclodextrin‐based chiral stationary phases in the normal‐phase HPLC.     

Synthesis and Structure/Property Relationships of Regioselective 2‐O‐, 3‐O‐ and 6‐O‐Ethyl Celluloses

Regioselectively ethylated celluloses, 2‐O‐ ( 1 ), 3‐O‐ ( 2 ), and 6‐O‐ethyl‐ ( 3 ) celluloses were synthesized via ring‐opening polymerization of glucopyranose orthopivalate derivatives. The number‐average degrees of polymerization (DP_ns) of compounds 1 and 2 were calculated to be 10.6 and 49.4, respectively. Three kinds of compound 3 with different DP_ns were prepared: DP_ns = 12.9 ( 3‐1 ), 60.3 ( 3‐2 ), and 36.1 ( 3‐3 ). The 2‐O‐, 3‐O‐, and 6‐O‐ethylcelluloses were soluble in water, confirmed by NMR analysis. Furthermore, the 3‐O‐ ( 2 ), and 6‐O‐ethyl‐ ( 3‐2 ) celluloses showed thermo‐responsive aggregation behavior and had a lower critical solution temperature (LCST) at about 40 °C and 70 °C, respectively, based on the results from turbidity tests and DSC measurements. The 6‐O‐ethyl‐cellulose ( 3‐3 ) with DP_n = 36.1 and DP_w = 54.6 showed gelation behavior over approx 70 °C, whereas the 6‐O‐ethyl‐celluloses 3‐1 and 3‐2 with lower and higher molecular weight, such as DP_ns 12.9 and 60.3, did not show gelation behavior at this temperature. It was revealed that the position of ethyl group affected the phase transition temperature. According to our experiments, the 3‐O‐ethyl and 6‐O‐ethyl groups along the cellulose chains caused the thermo‐responsive property of their aqueous solutions. The appropriate DP of the regioselective 6‐O‐ethyl‐cellulose existed for gelation of the aqueous solution.

     

Influence of substituent position and cavity size of the regioisomers of monocarboxymethyl‐α‐, β‐, and γ‐cyclodextrins on the apparent stability constants of their complexes with both enantiomers of Tröger's base

Enantiomers of Tröger's base were separated by capillary electrophoresis using 2^I‐O‐, 3^I‐O‐, and 6^I‐O‐carboxymethyl‐α‐, β‐, and γ‐cyclodextrin and native α‐, β‐, and γ‐cyclodextrin as chiral additives at 0–12 mmol/L for β‐cyclodextrin and its derivatives and 0–50 mmol/L for α‐ and γ‐cyclodextrins and their derivatives in a background electrolyte composed of sodium phosphate buffer at 20 mmol/L concentration and pH 2.5. Apparent stability constants of all cyclodextrin–Tröger's base complexes were calculated based on capillary electrophoresis data. The obtained results showed that the position of the carboxymethyl group as well as the cavity size of the individual cyclodextrin significantly influences the apparent stability constants of cyclodextrin–Tröger's base complexes.     

The study of enantioselectivity of all regioisomers of mono‐carboxymethyl‐β‐cyclodextrin used as chiral selectors in CE

This work documents the influence of the position of single carboxymethyl group on the β‐cyclodextrin skeleton on the enantioselectivity. These synthesized monosubstituted carboxymethyl cyclodextrin (CD) derivatives, native β‐cyclodextrin, and commercially available carboxymethyl‐β‐cyclodextrin with degree of substitution approximately 3 were used as additives into the BGE consisting of phosphate buffer at 20 mmol/L concentration, pH 2.5, and several biologically significant low‐molecular‐mass chiral compounds were enantioseparated by CE. The results indicate that different substituent location on β‐cyclodextrin skeleton has a significant influence on the enantioseparation of the investigated enantiomers. The enantioselectivity of 2^I‐O‐regioisomer was better than with native β‐cyclodextrin. Comparable results to native β‐cyclodextrin were obtained for 6^I‐O‐ regioisomer and the enantioselectivity of 3^I‐O‐regioisomer was even worse than with native β‐cyclodextrin. Commercially available derivative of CD provides better resolutions than the monosubstituted carboxymethyl CD derivatives for most of the investigated analytes.     

Synthesis of benzyl O-(2,3,3'-tri-O-acetyl-β-D-apiofuranosyl)-(1→3)-2,4-di-O-benzoyl-α-D-xylopyranoside and its X-ray structure

The protected apiose-containing disaccharide, benzyl O-(2,3, 3'-tri-O-acetyl-β-D-apiofuranosyl)-( 1→3)-2, 4-di-O-benzoyl-α-D-xylopyranoside, was synthesized and its X-ray structure provided.     

First Synthesis of 3‐O‐Functionalized Cellulose Ethers via 2,6‐Di‐O‐Protected Silyl Cellulose

The present paper describes the synthesis of 2,6‐di‐O‐thexyldimethylsilyl cellulose as a novel 2,6‐di‐O‐protected cellulose derivative. This material was obtained by reacting cellulose in N,N‐dimethylacetamide/LiCl solution with thexyldimethylchlorosilane and imidazole for 24 h at 100°C. In a typical subsequent reaction the residual OH‐group in position 3 could be completely etherified without loss of any protecting groups. Treatment with tetrabutylammonium fluoride leads to the novel compounds 3‐O‐allyl and 3‐O‐methyl cellulose. The structures of all polymers are revealed by means of one‐ (¹H and ¹³C) and two‐dimensional (COSY and HMQC) NMR techniques.     

O‐Ethyl and O‐methyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐glucopyranosyl)thiocarbamate

In both the title structures, O‐ethyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d ‐gluco­pyran­osyl)­thio­carbam­ate, C₁₇H₂₅NO₁₀S, and O‐methyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d ‐gluco­pyran­osyl)­thiocar­bam­ate, C₁₆H₂₃NO₁₀S, the hexo­pyran­osyl ring adopts the ⁴C₁ conformation. All the ring substituents are in equatorial positions. The acetoxy­methyl group is in a gauche–gauche conformation. The S atom is in a synperi­planar conformation, while the C—N—C—O linkage is antiperiplanar. N—H?O intermolecular hydrogen bonds link the mol­ecules into infinite chains and these are connected by C—H?O interactions.     

catena‐Poly[[(acetato‐κ2O,O′)triaquabarium(II)]‐μ3‐acetato‐κ4O:O,O′:O′]

The present form of barium acetate, formulated as [Ba(C₂H₃O₂)₂(H₂O)₃]_n, is the largest reported hydrate of the salt and this leads to a distinct structural behaviour setting it apart from the rest of the family. The compound is a linear polymer with a nine‐coordinate Ba(O_aqua)₃(O_acetate)₆ monomer unit. The non‐H part of the structure is ordered according to C2/m symmetry, while the disordered water H atoms only abide by this symmetry in a statistical sense. Each molecule is halved by a mirror plane bisecting the Ba centre, one water molecule and one acetate ligand, while containing the other acetate ligand. The chains are interconnected by a disordered water–water/acetate O—H...O hydrogen‐bonding network involving all water H atoms. The structure and stability of this phase are compared with the other known acetates of barium which differ in the degree of hydration.     

Veronicafolin－β-环糊精的物化表征及Veronicafolin－羟丙基-β-环糊精包合物溶解性的增强

用氢谱、红外光谱、X-射线粉末衍射、热分析、元素分析等测试方法研究了Veronicafolin (3,5,4′-三羟基-6,7,3′-三甲氧基黄酮) 和β-环糊精 (β-CD) 的固体包合物的谱学特征。元素分析结果显示形成Veronicafolin-β-CD·20H2O包合物，其中C：39.58%, H: 5.75%，表明包合物中主客体比为1∶1。该包合类型属于A_L-型。通过紫外-可见分光光度法研究了在羟丙基-β-环糊精（HP-β-CD）的存在下Veronicafolin的相溶解度曲线，测得校正曲线为y = 24148x + 0.0075 (r=0.9999)，相溶解曲线为y=0.4738x-2.0×10^-7 (r=0.9490)，包结平衡常数Ks为4.5×10⁶mol-1。HP-β-CD提高了黄酮醇Veronicafolin的溶解度。     

β‐Cyclodextrin‐modified three‐dimensional graphene oxide‐wrapped melamine foam for the solid‐phase extraction of flavonoids

A new three‐dimensional graphene oxide‐wrapped melamine foam was prepared and used as a solid‐phase extraction substrate. β‐Cyclodextrin was fabricated onto the surface of three‐dimensional graphene oxide‐wrapped melamine foam by a chemical covalent interaction. In view of a specific surface area and a large delocalized π electron system of graphene oxide, in combination with a hydrophobic interior cavity and a hydrophilic peripheral face of β‐cyclodextrin, the prepared extraction material was proposed for the determination of flavonoids. In order to demonstrate the extraction properties of the as‐prepared material, the adsorption energies were theoretically calculated based on periodic density functional theory. Static‐state and dynamic‐state binding experiments were also investigated, which revealed the monolayer coverage of flavonoids onto the β‐cyclodextrin/graphene oxide‐wrapped melamine foams through the chemical adsorption. ¹H NMR spectroscopy indicated the formation of flavonoids–β‐cyclodextrin inclusion complexes. Under the optimum conditions, the proposed method exhibited acceptable linear ranges (2–200 μg/L for rutin and quercetin‐3‐O‐rhamnoside; 5–200 μg/L for quercetin) with correlation coefficients ranging from 0.9979 to 0.9994. The batch‐to‐batch reproducibility (n = 5) was 3.5–6.8%. Finally, the as‐established method was satisfactorily applied for the determination of flavonoids in Lycium barbarum (Goji) samples with relative recoveries in the range of 77.9–102.6%.     

Synthesis of an analog of ( )-goniopypyrone from 3- O- benzyl-1,2- O-isopropylidene-5- C-phenyl-α-D-gluco-pentofuranose

8,9-Dimethoxy-7-epi-goniopypyrone, an analog of ( )-go-niopypyrone, was synthesized from 3-O-benzyl-1, 2-O-iso-propylidene-5-C-phenyl-α-D-gluco-pentofuranose (3).     

Synthesis and Properties of O‐β‐D‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐ O‐phosphate and Its Derivatives

The efficient synthesis of O‐β‐D ‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐O‐phosphate and O‐β‐D ‐ribofuranosyl‐(1″→2′)‐adenosine‐5″‐O‐phosphate, minor tRNA components, have been developed, and their conformational properties were examined by NMR spectroscopy.