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%).     

Investigation on the Interaction of Bendazac with β-, Hydroxypropyl-β-, and γ-, yclodextrins

The interactions of Bendazac, a topical non-steroidal anti-inflammatory drug, with-cyclodextrin, hydroxypropyl--cyclodextrin and -cyclodextrinwere investigated to evaluate possibilities to improve the drug's poor water solubilityand eventually to enhance the topical delivery of Bendazac. Phase solubility studiesdemonstrated the ability of the selected cyclodextrins to complex with Bendazac andincrease drug solubility. The amount of solubilized Bendazac increased linearly withthe addition of each cyclodextrin according toA_L type plots. ¹³C-NMR studiesshowed that the Bendazac A-ring was included in the cavity of the three cyclodextrins.The -cyclodextrin was also able to include the B-ring of Bendazac, forminga complex where one drug molecule fitted into two cyclodextrin molecules. Equimolarsolid systems of the drug with each cyclodextrin carrier were prepared using varioustechniques (physical mixing, spray-drying and freeze-drying). The results of differential scanning calorimetry and Fourier transform infrared analysis, performed on the solid systems, demonstrated that freeze-dried and spray-dried products had a high degree of amorphization and agreed with the hypothesis of the existence of drug–cyclodextrin interaction in the solid state. The cyclodextrins tested were able to improve the dissolution of Bendazac. The dissolution profile of the drug was also affected by the physico-chemical properties of each solid system, the freeze-dried products being the most rapidly dissolving forms.     

Interactions of amphiphilic drugs withα-,β-, andγ-cyclodextrins

The association of several amphiphilic drugs with -, -, and -cyclodextrins has been measured by use of drug-sensitive electrodes. Drugs investigated are hydrochlorides of chlorpromazine, dibucaine, tetracaine, and procaine, and valethamate bromide. Each drug forms the drug:cyclodextrin=11 complex with - and -cyclodextrin, and both the 11 and 21 complex with -cyclodextrin, except valethamate which only forms the 11 complex. The strength of the 11 complex formations is in the order of CyD>-CyD>-CyD. The association constant of the 21 complex in drug--CyD is larger than that of 11 complex. The free energy change of the conplex formation has a positive correlation with that of the micelle formation of drugs. The deviation from this relation is explained in terms of fittability of the bulky hydrophobic group of drugs into the cyclodextrin's cavity. The free energy change for the complex formation between chlopromazine or valethamate and -CyD is governed by the enthalpy term and not by the entropy term which controls the surfactant--CyD interactions.     

On the origin of the relative stability of Wells-Dawson isomers: a DFT study of α-, β-, γ-, α*-, β*-, and γ*-[(PO4)2W18O54](6-) anions

Density functional theory calculations have been carried out to investigate α-, β-, γ-, α*-, β*-, and γ*-[(PO(4))(2)W(18)O(54)](6-) Wells-Dawson isomers, which exhibited stability in the order of α > β > γ > γ* > β* > α*, reproduced the experimental observations (α > β > γ), and confirmed the hypothesis of Contant and Thouvenot (γ* > β* > α*). Energy decomposition analysis reveals that both the spatial arrangement of the host W(18)O(54) cage (eclipsed or staggered) and its structural distortion induced by the encapsulated guest anions are two dominant factors in control of the stability order, while the influences of host-guest interaction and distortion of the guest anions are very small. A building block decomposition approach is designed and provides an effective means to clarify the detailed relationship between the local distortion and energy. By using this method, it is found that the eclipsed belt, and in particular the staggered belt, significantly distort the two caps inside the Wells-Dawson structure. Notably, there is a direct relationship between the overall stability and distortion in the belts, which is proven to be partly originating from the dominance in the quantity of the belt building blocks over that of the caps (12:6). Besides, half-unit {XW(9)} decomposition confirms that [(XO(4))(2)W(18)O(54)](n-) (X = Si, Ge, Al, and Ga) are thermodynamically instable because of the notable electrostatic repulsion between two {XW(9)} units induced by the highly charged guest anions.     

Impact of α-, γ-, and δ-tocopherol on the radiation induced oxidation of rapeseed oil triacylglycerols

Gamma-irradiation (doses: 2, 4, 7, and 10 kGy) was used as oxidation tool to study the antioxidant effects of α-, γ-, and δ-tocopherol (enrichments 500–5000 ppm) in purified rapeseed oil triacylglycerols (RSOTG). Fatty acid composition, tocopherol degradation, primary (conjugated dienes (CD) and peroxide value (POV)) and secondary (p-anisidine value) oxidation products were chosen as test parameters. Fatty acid composition did not change. While secondary oxidation products could not be found in the irradiated samples, the POVs and CDs showed a significant, dose-dependent increase. α-Tocopherol did not inhibit the formation of peroxides, whereas γ- and δ-tocopherol reduced the POVs by more than 30%. No uniform effect of the different tocopherol concentrations at the particular doses could be established. The influence of the individual tocopherols on the CD formation was not pronounced. The degradation of the tocopherols decreased with increasing concentration. None of the tocopherols showed a prooxidant effect.     

Preparation of both enantiomers of β-(3,4-dihydroxybenzyl)-β-alanine, higher homologues of Dopa

β²-(3,4-Dihydroxybenzyl)-β-alanine [β²-Homo-Dopa, 1] is a novel β-amino acid homologue of Dopa, the most successful therapeutic agent in the treatment of Parkinson's disease. Enantioenriched (R)-1 and (S)-1 were obtained via the diastereoselective alkylation of enantiopure pyrimidinone (R)- and (S)-3, chiral derivatives of β-alanine, with veratryl iodide. The major diastereomeric products (2S,5R)-4 and (2R,5S)-4 were hydrolyzed with 57% HBr, and the desired β-amino acids were purified by silica gel chromatography. Alternatively, enantioenriched (R)- and (S)-1 were prepared by means of the highly diastereoselective alkylation (3,4-dimethoxybenzyl iodide) of open-chain β-aminopropionic acid derivatives (R,R,S)-8 and (S,S,R)-8 containing the chiral auxiliary α-phenylethylamine. Finally, nearly enantiopure (R)- and (S)-1 were obtained by resolution of racemic N-benzyloxycarbonyl-2-(3,4-dibenzyloxybenzyl)-3-aminopropionic acid, rac-12, with (R)- or (S)-α-phenylethylamine, followed by catalytic hydrogenolysis.     

Solubility of Oxygen in Some 1-1, 2-1, 1-2, and 2-2 Electrolytes as a Function of Concentration at 25°C

The solubility of oxygen has been measured in a number of electrolytes [(LiCl, KCl, RbCl, CsCl, NaF, NaBr, NaI, NaNO₃, KBr, KI, KNO₃, CaCl₂, SrCl₂, BaCl₂, Li₂SO₄, K₂SO₄, Mn(NO₃)₃)] as a function of concentration at 25°C. The solubilities, mol (kg-H₂O)^–1, have been fitted to a function of the molality m (standard deviation < 3mol-kg^–1)

Total Syntheses of 11-Acetoxy-4-deoxyasbestinin D, 4-Deoxyasbestinin C,Asbestinin-10, -20, -21 and -23

Six members of the asbestinin family of marine diterpene natural products have been synthesized in an efficient and stereoselective manner from a single oxa-bridged intermediate. Five of these natural products have not been synthesized previously and the structures of four of them have been confirmed as those proposed originally or following revisions to the original structures. The fifth natural product—asbestinin-21—has been shown to be a diastereomer of the compound that had been proposed previously.     

A simple molecular-orbital study of theβ-,α-, and p-bands in triphenylenes

Clar has observed that the spectra of annellated derivatives of triphenylene such as II, III, IV below show remarkable resemblance to those of the phenes defined by the central ring of the triphenylene and its two longest acene limbs, II resembling tetraphene I, and III and IV pentaphene V. We show that this observation can be explained in terms of a simple modification of the Hückel molecular-orbital method.

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Zusammenfassung Eine Beobachtung von Clar hat gezeigt, daß die Spektren der Benzologen des Triphenylens, wie z. B. II, III, IV außerordentlich ähnlich sind denen der Phene, die ausgehend vom zentralen Ring und den beiden längsten Armen der obigen Systeme gebildet werden. Daher ähnelt das Spektrum von II stark dem des Tetraphens I und die von III und IV dem des Pentaphens V. Es wird gezeigt, daß dieser Beobachtung durch eine einfache Modifikation der Hückelschen MO-Theorie Rechnung getragen werden kann.

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Résumé Clar a observé que les spectres d'absorption des dérivés annelés du triphénylène tels que, II, III et IV montrent une ressemblance extraordinaire à ceux des phènes définis par l'anneau central du triphényléne et ses deux armes les plus longues. Ainsi le spectre de II ressemble à celui du tétraphène et ceux de III et de IV à celui du pentaphène V. Nous avons démontré qu'on peut expliquer cette observation par une modification simple de la méthode des orbitales moléculaires d'Hückel.

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We gratefully acknowledge many helpful discussions with Dr. E. Clar and Dr. J.-F. Guye-Vuilléme and the award of a D. S. I. R. Maintenance Grant to one of us (D. A. M.-B.). Chemistry Department, University of Glasgow.     

Steric effects in the catalytic amination of γ-, δ-, and ε-glycols

The amination of butane-1,4-diol, isomeric dipropylene glycols, and cyclohexane-1,4-diyldimethanol in the presence of nickel/copper/chromium catalysts has been studied. The effect of the initial glycol structure on the reaction selectivity has been estimated.     

Binding behaviors of scutellarin with α-, β-, γ-cyclodextrins and their derivatives

A series of cyclodextrin/scutellarin inclusion complexes were prepared from α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with scutellarin (SCU), and their inclusion complexation behaviors, such as stoichiometry, complex stability constants and inclusion mode, were investigated by means of UV/Vis spectroscopy, ¹H NMR and 2D NMR. The results showed that the SCU could be efficiently encapsulated in the cyclodextrin cavity in aqueous solution to produce complexes that were more soluble than free SCU. The enhanced binding ability of cyclodextrins towards SCU was discussed from the viewpoint of the size/shape-fit and multiple recognition mechanism between host and guest.     

Studies on Mechanism of Chemiluminescence Reaction of 2, 6, 7-Trihydroxyl-9-(4'-chlorophenyl )-3-fluorone

1INTRoDUCTIONPhenylfluoroneisanimportanttypeofreagentinanalytica1chemistry"~'>.Themoleculesofthisreagenthavearigidplanarstructuret5'6i,sotheenergyofmolecularorbitsofthereagentscanbecalculatedbyHuckelmolecularorbitalmethod(HMO).WehadtriedtoassigndissociationconstantsforsomesuchreagentsbyacombinedspectrophotometricandHMOmethodt7'8i.Them.thodissimpleandtheresultsaresatisfactory.Inthispaper,apossiblemechanismforcatalyticchemiluminescencere-actionofCl-PFisproposedonthebasisofstudyingchemil…     

A Convenient Synthesis of 2, 3 - DI- O - Acetyl-1, 6 - Anhydro- β - D – Glucopyranose

Abstract

1, 2, 3-Tri-O-acetyl-6-O-benzyl-4-O-chloroacetyl-α- and -β-D-glucopyranose (4α β)were derived from 1, 2, 3-tri-O-acetyl-4, 6- O -benzyl-idehe-β-D-giucopyranose (1) in two steps. Compound 1, 1, 2, 3-tri-O -acetyl-β-D-glucopyranose (2), and 4α,β were subjected to the cyclization reaction using Lewis acids ( SnCl₄ and BF₃-etherate), to give corresponding 1, 6-anhydro derivatives.     

Complexes of α-, β-, and γ-cyclodextrins with nitrophenols: A theoretical study of the structure and energy

Detailed quantum mechanical calculations of the interaction of cyclodextrin (α-, β-, and γ-CD) with 4-nitrophenol (I), 4-nitro-2,6-dimethylphenol (II), 4-nitro-3,5-dimethylphenol (III), and their anions (IVVI) with the formation of intercalation complexes are carried out for the first time. The calculations of the compounds are performed within the density functional theory by the hybrid Becke–Lee–Yang–Parr (B3LYP) method with LanL2DZ basis sets. For the α-CD+III and α-CD+VI complexes it is shown that a nitrophenol molecule of III and a nitrophenolate anion of VI are not contained in the α-CD torus, which agrees with the experimental equilibrium constants. It is found that the calculated equilibrium constants of the formation of guest–host complexes with phenolate anions are much larger than those of neutral molecules. The most stable CD complexes with nitrophenols and their anions should be expected for γ-CD. The β-CD complexes when the guest enters into the host cavity are formed only with compounds I, V, and VI.     

The Crystal Structure of 1, 4, 7, 10- Tetraazacyclododecane Hydrate Triperchlorate

1=mTRODUCTIONMacroazacyclicligandisofwideinterestbecauseofitsstructuralsimilaritywiththeskeletonofPOrphyrinringinsomebibectivesubstancessuchaschlorophyllandhemeetc.tl1.Asametalsimulationenzyme,macroazacyclicligandcoordinatedwithtransitionmetalhasbeeninvestigatedthoroghlyinkinetic,dynamicandstructuralcharactert2.3).Butthere'isnorePOrtaboutthecrystalstructureof1,4,7,1o-tetraaza-cyclododecanehydratetriperchlorate.2EXPERIMENTAL2-lSynthesisoftheTitleComplexTetraazacycldodecanewassynthes…     

Distribution of α-, β-, and γ-Phases in a Multi-flow Injection-molded Hierarchical Structure

In the current work, a custom-made vibration injection molding device that can provide oscillatory pressure was utilized to create an injection-molded hierarchical structure. Growth competition among α, β, and γ phases in the injection-molded structure can be studied because of the presence of this hierarchical structure, wherein shish-kebab and spherulite layers were arranged alternately along the thickness direction. The γ crystals only existed in layers subjected to high pressure and shear stress, whereas β crystals formed between the shear layers. The change in trend of the γ fraction was similar to that of parent-to-daughter ratio. In addition, this hierarchical and alternating crystal structure can sharply increase the mechanical properties.     

Samarium diiodide induced cyclizations of γ-, δ- and ε-indolyl ketones: reductive coupling, intermolecular trapping, and subsequent transformations of indolines

This comprehensive study describes our results of samarium diiodide induced 5-exo-trig to 8-exo-trig cyclization/alkylation sequences of 3'-acceptor-substituted indolyl ketones. All cyclization precursors were easily prepared by simple N-alkylation or N-acylation of indole derivatives with the corresponding iodo alkanones, acid chlorides, or lactones. After treatment of indolyl ketones with two equivalents of SmI(2), the generated stabilized carbanionic intermediates were trapped with different electrophiles leading to a variety of highly substituted indoline derivatives in good to very good yields. In general, the cyclization products were obtained as single diastereomers bearing a newly generated quaternary center, a common structural motif in various indole alkaloids. The relative configurations of the products were established by NOE experiments and by single-crystal analysis and follow the rules already established. Furthermore, the obtained products were subjected to a series of chemical transformations, such as oxidation, reduction, and metathesis reactions resulting in a range of interesting synthetic building blocks valuable for further applications.