The Influence of β-Cyclodextrins on the Solubility of Furosemide

Furosemide (F) is practically insoluble in water (10.26 mg/100 mL).Different -cyclo- dextrins (-CD derivatives) were applied ashost to improve the solubility of furosemide as guest molecule via inclusioncomplex formation. Various molar ratios of F : -CD derivatives (1 :1/2, 1 : 1 and 1 : 2) and different preparative methods (physical mixing,kneading, precipitation, spray-drying and freeze-drying) were used. Theincrease in the dissolution characteristics and the solubility of furosemidedepends on the type of -CD derivative, on the furosemide concentrationin the product and on the method of preparation. The inclusion complexesformed between the hosts and the guest were investigated by XRD, IR, and¹H-NMR spectral methods.     

Study on the Reaction of α-Ketohemithioacetal

Aromatic α-sulfinyl carboxylic acids can be rearranged to hemithioacetals or other derivatives of glyoxylic acid under the action of acid reagents was first reported by Pummerer¹. Later, Russell and coworkers applied this rearrangement to β-ketosulfoxides, synthesized α-ketohemithioacetal², which can be transformed to α-keto alcohol, α-keto aldehyde and α-hydroxy alcohol, α-hydroxy acid³. Furthermore, Hall and Poet reported that α-ketohemithio-acetal can be rearranged to the corresponding α-hydroxythioester in the presence of magnesium nitrate and sodium acetate or tertiary amine⁴. However, few reports of reaction of α-ketohemithioacetal can be seen in literature.     

Study on the Reaction of α-Thiobenzoylthioformylmorpholine

a-ThiocaIbonylthiOformnddesareOfalmostunexploredclassOfcomPOundsll],althoughtheyhavebeenpreParedsincel98Ol2-3].ThisattractSustoexploretheirchendStryandutilityinSynthesisOfheteropcles.Accordingtoourpreviousmethodl`1,a-benzOylthiOfOrmyl-morpholine1wasprePaIedfirst,fOllowedbysumirizationOfcarbonylwithLawessenreagnttoaffordtheexpeCtedcr-thjobenzoylthiOformylmorpholine2,whchhastWothiotnylgrous.onthebasisOfstructUreof2,itcanbereactedwithcomPOundsbearingdrinctionalgrouP,suchasdidrineandsen…     

Complexation of Monosulfonated Triphenylphosphine with Chemically Modified β-Cyclodextrins: Effect of Substituents on the Stability of Inclusion Complexes

Interactions between the meta-substituted monosulfonated triphenylphosphine and chemically modified β-cyclodextrins were investigated in aqueous solution by NMR and UV–vis spectroscopy. Titration and continuous variation plots obtained from ³¹P NMR data indicate that the monosulfonated triphenylphosphine forms 1:1 inclusion complexes with the 2-hydroxypropylated β-cyclodextrin, the methylated β-cyclodextrin and the (2-hydroxy-3-trimethylammoniopropyl)-β-cyclodextrin chloride. These inclusion complexes are more stable that those formed with native β-cyclodextrin, confirming that poisoning of the chemically modified β-cyclodextrins by the hydrosoluble phosphine occurs when modified cyclodextrins are used as mass transfer promoters in aqueous-phase organometallic catalysis.This revised version was published online in July 2005 with a corrected issue number.     

Complexation of the Non-steroidal Anti-inflammatory Drug Loxoprofen with Modified and Unmodified β-Cyclodextrins

The inclusion complex of the anti-inflammatory drug, loxoprofen, with -cyclodextrin-(CD), sulfated -CD, and glycerol ether -CD was studied by UV-VIS absorption and ¹H-NMR spectroscopy in solution. The inclusion complex of loxoprofen with -CDs was prepared by freeze-drying, and then characterized in the solid state by thermal analysis, X-ray diffraction, FT-IR and FT-Raman spectroscopy, and scanning electron microscopy (SEM). Furthermore, a physical mixture of loxoprofen/-CD (1/1, mol-%) in the solid state was also characterized. The solubility of the loxoprofen increased on addition of -CDs. The solubility enhancement of the loxoprofen with -CDs is in the following order: glycerol ether -CD > sulfated -CD > -CD.     

Correlation between Thermodynamic Behavior and Structure in the Complexation of Modified β-Cyclodextrins and Bile Salts

Complex stability constants (K _S), standard molar enthalpy changes (ΔH ⁰) and entropy changes (ΔS ⁰) for the inclusion complexation of two cyclodextrin dimers, 6,6′-{2,2′-diselenobis[2-(benzoylamino)ethylamino]}-bridged bis(β-cyclodextrin) (1) and o-phenylenediseleno bridged bis(β-cyclodextrin)s (3), and their monomer analogs, 6-deoxy-6-{[2-(2,3-dihydro-3-oxo-1,2-benzisoselenazol-2-yl)ethyl]amino}-β-cyclodextrin (2) and mono[6-(phenylseleno)-6-deoxy]-β-cyclodextrin (4), with two bile salt guests, sodium cholate (CA) and sodium deoxycholate (DCA), were determined at 25°C in Tris buffer solutions (pH 7.4) at 298.15?K by means of isothermal titration microcalorimetry (ITC). The interactions and binding modes between the host cyclodextrins and the guest bile salts were further studied by ROESY spectroscopy. The thermodynamic parameters obtained, together with the ROESY spectra, were used to examine the correlations between thermodynamic behavior and binding modes of the host–guest complexation. The results indicate that the length, structure and conformation of the tethers linked to the cyclodextrins determine the binding modes and the binding abilities between hosts and guests to a great extent, leading to a reversion in binding ability when comparing the corresponding dimer and its monomer analog.     

Molecular Binding Ability and Selectivity of Natural α-, β-, γ-Cyclodextrins and Oligo(ethylenediamino) Modified β-Cyclodextrins with Chinese Traditional Medicines

The binding ability andinclusion complexation behavior of natural -, -, -cyclodextrins (1–3) and two mono[6-oligo(ethylenediamino)-6-deoxy]--cyclodextrins(4, 5) with fourChinese traditional medicines, that is, -asarone (AS), ferulic acid (FA), magnolol (MA) and honokiol (HO), have been investigated in aqueous phosphate buffer solutions(pH = 7.20). The spectral titrations have been performed at 25 °C by using fluorescence spectroscopy to calculate the complex stability constants (K_S) and Gibbs free energy changes ( G°) for the stoichiometric 1 : 1 inclusion complexation of hosts1–5 with guest medicines. The results obtained indicate that the different guest medicines fit in with hydrophobic cavities of different sizes and the appended substitutes of hosts 4 and 5 change the hydrophobic microenvironment of -cylcodextrin 2, influencing the original binding ability and molecular selectivity of host 2 consequently. The binding ability and inclusion complexation behavior of these hosts 1–5 are discussed according to the size/shape fit concept and hydrogen bonding interaction between host cyclodextrins and guest medicine molecules.     

Enzymatic Resolution of Ethyl α-Hydroxyphosphinates in a Modified Reaction Environment

The enzymatic resolutions of two racemic ethyl hydroxyalkane(P-phenyl)phosphinates were performed by both esterification and hydrolysis approaches. The first reaction was performed in anhydrous diisopropyl ether with triethylamine or pyridine as additives by using lipases from three different sources (Candida cylindracea, Aspergillus niger, and Mucor javanicus). The increase in enantioselectivity was observed when NEt₃ was applied. The second reaction—lipase-catalysed hydrolysis of ethyl butyryloxyalkane(P-phenyl)phosphinates—was carried out by Candida cylindracea lipase in diisopropyl ether saturated with water or in aqueous solutions containing MgCl₂, LiCl, or Triton X-100. The usefulness of biphasic systems consisting of diisopropyl ether and water or aqueous solution of MgCl₂, LiCl, or Triton X-100 also were tested. The use of biphasic system in the presence of Triton X-100 resulted in the higher conversion of the substrates.     

Role of Mononuclear Rare Earth Metal Complexes in Promoting the Hydrolysis of 2-Hydroxypropyl p-Nitrophenyl Phosphate

Two long-chain multidentate ligands： 2,9-di-（n-2＇,5＇,8＇-triazanonyl）-1,10-phenanthroline （L^1） and 2,9-di- （n-4＇,7＇,10＇-triazaundecyl）-1,10-phenanthroline （L^2） were synthesized. The hydrolytic kinetics of 2-hydroxypropyl p-nitrophenyl phosphate （HPNP） catalyzed by the complexes of L^1 or L^2 with La（Ⅲ） or Gd（Ⅲ） have been studied in aqueous solution at （298.2±0.1） K, I=0.10 mol·dm^-3 KNO3 in pH 7.5-9.1, respectively, finding that the catalytic effect of GdL^1 was the best among the four complexes for hydrolysis of HPNP. Its kLnLH-1, kLnLand pKa are 0.047 mol^-1·L·s^-1, 0.000074 mol^-1·L·s^-1 and 8.90, respectively. This paper expounded the studied result with the structure of the ligands and the properties of the metal ions, and deduced the catalysis mechanism.     

Selective Modification of β-Cyclodextrin on the Secondary Side 4:Preparation of Arylated β-Cyclodextrins with a Flexible Chain

Cyclodextrins(CDs,includinga-,o-,a-CD,etc.)havegainedprominenceinrecentyearsbecauseoftheirtorus-shapedcavity,whichishydrophilicoutsideandhydrophobicinside,caPableofprovidingidealprototypestoconstructefficientartificialenzymes,molecuIarrecognitionsensorsandotherfunctionalmodels.l-3Forbuildingmoreefficientartificialenzymesandmolecularrecognitionsensors,wehavepreparedaseriesof6-CDderivativesbearingchromophores'-'andfoundthat3"-'anarylmoietycouldactasaspectrometryprobeaswellasafunctionalgroup.F…     

Direct Synthesis of Amphiphilic α-, β-, and γ-Cyclodextrins

ABSTRACT

The clean one step synthesis of the amphiphilic α-, β-, and γ-cyclodextrins starting from per-(6-bromo-6-deoxy)-α-, -β-, and -γ-cyclodextrins is described. The role of the lipophilic tail is played by various aryl groups (phenyl, p-bromophenyl, p-O-butoxyphenyl, p-pentylphenyl, and o-, m-, and p-nitrophenyl) linked by a thioether bridge to the position C-6 of each glucopyranose unit. The yields of the S-alkylation reactions were very high (85-95%).     

Reaction of 2-aminopyridines with α, β-unsaturated acids

The reaction of 2-amino- and 2-amino-5-halopyridines with acrylic, methacrylic, and crotonic acids forms N-(2-pyridyl)- and N-(5-halo-2-pyridyl)--alanines and the betaines 2-amino-1-(2-carboxylatoethyl)pyridinium or 3,4-dihydropyrido[1,2-a]pyrimidin-2-ones, or their homologs.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 80–85, January, 1992.     

Studies on the Silylation Reaction of α,β-Epoxy Esters Synthesized by Darzen's Condensation Reaction

Me₃SiCl/Mg in HMPA was used for silylation of α,β-epoxy esters resulting in the corresponding β-silylated esters in a one pot reaction with reasonable yields.     

Effects of substituent and solvent on the Sonogashira coupling reaction of β-bromoporphyrin

A series of experiments were designed to understand the effects of substituent and solvent on the Sonogashira coupling reaction of β-bromoporphyrin using a Pd₂(dba)₃/AsPh₃ system as the catalyst. Electron-efficient groups and aprotic solvents are conducive to the reaction. A possible explanation was given. A new family of β-pyrrole substituted porphyrins was also synthesized during the study.     

A Convenient Procedure for the Synthesis of 6-O-Mono-Phosphate β-Cyclodextrins

Abstract

The synthesis of β-cyclodextrin derivatives bearing one phosphate group on the primary rim is reported. These compounds were prepared in good to excellent yields, by reacting β-cyclodextrin with dialkyl chlorophosphates in the presence of 4-dimethyl amino pyridine (DMAP) catalyst and dimethylformamide (DMF) as solvent. The methodology described is highly selective and the purification of the title compounds is simple, because difficulties due to phosphate regioisomers mixture are avoided.     

Guest-Binding and Catalytic Properties of Immobilized β-Cyclodextrins

Abstract

Cyclodextrins¹(CyDs), cyclic oligomers of 6–8 glucose units, form inclusion complexes with guest compounds and have been used as catalyst for the selective syntheses.² Previously, immobilization of CyD with epichlorohydrin as crosslinking agent have been described.^3-4 Here, we report the first successful immobilization of β-CyD using various crosslinking agents. The guest binding abilities and the catalytic abilities of these immobilized β-CyDs are shown.     

Stereoelectronic Effects on the Nucleophilic Addition of Phosphite to the Carbonyl Double Bond: Ab Initio Molecular Orbital Calculations on Reaction Surfaces and the α-Effect

Ah initio molecular orbital calculations have been carried out on adducts of trihydroxy phosphine, P(OH)₃, and formaldehyde, H₂C=0. Stationary points were located and a reaction surface calculated. One stationary point exists as a stable pentacovalent phosphorane, and the other as a 1,3-dipolar transition state. Calculations differing in the conformation about the P-OH bonds of the phosphite reveal that an antiperiplanar (app) lone pair on oxygen to the phosphorus lone pair (acyclic analogue) raises the energy of the molecule by 1.7 kcal/mol relative to a phosphite conformation with no app lone pairs to the phosphorus lone pair (bicyclic analogue). In the transition state, the relative energy between the two conformations reverses with the acyclic analogue transition state 5 kcal/mol lower energy than the bicyclic analogue transition states. The lower energy for the acyclic analogue in the transition state is attributed to the mixing of the app lone pairs on the oxygens of the phosphite mixing with the σ orbital of the newly formed bond between phosphorus and carbon. This kinetic Stereoelectronic effect can explain why acyclic phosphites react much faster in nucleophilic reactions than bicyclic phosphites. This phenomenon suggests that the origin of the α-effect, the enhanced nucleophilicity of a base possessing a heteroatom with an adjacent unshared electron pair arises from the stereoelectronic effect.     

Synthetic Potential of the Reaction of Allylic Phosphonium Ylides with α, β-Unsaturated Carbonyl Compounds

The reaction of triphenylphosphonium-2-propenylide (14) with mesityl oxide (9) is shown to proceed via initial Michael addition followed by trans ylidation and an intramolecular Wittig condensation to yield 1, 5, 5-trimethyl-1, 3-cyclohexadiene (10) as the reaction product.     

Kinetics of the Micellar Effects on the Alkaline Hydrolysis of 2-Chloro-quinoxaline in Acetonitrile-Water Mixtures at 35°C

Pseudo-first-order reaction rate for alkaline hydrolysis of 2-chloroquinoxaline (2-CQX) is carried out in acetonitrile (AN)-water (H₂O) mixtures at 35°C. Cationic surfactants as dodecyltrimethylammonium bromide (DOTAB) and an anionic surfactant as sodium dodecylsulphate (SDS) are used above their critical micelle concentration (cmc) to study the effect of micelles on reaction rate. When increasing the percentage of volume of AN, the rate profiles with DOTAB are shown to slightly increase with increasing surfactant concentration, while that with SDS are found to smoothly decrease. The micellar effect is explained in terms of a modified pseudo-phase ion exchange model. The binding constant (K_S) between 2-CQX and DOTAB as micelle showed a decrease by increasing percentage of volume of AN, while that with SDS increased. The counterion micellar coverage degrees (β) are found to be 0.55 and 0.85 with DOTAB and SDS systems, respectively, at all range of volume percentage of AN. Finally, the calculated ratio between rate constants in water to that in the micelle region k_w/k_M at different volume percentage of AN indicated that DOTAB enhances the reaction rate while SDS inhibits it.