Synthesis and ion selectivity of macrocyclic metacyclophanes analogous to spherand-type calixarenes

Novel macrocyclic compounds, hexahydroxy[1.0.1.0.1.0]- (2b) and octahydroxy[1.0.1.0.1.0.1.0]metacyclophane (2c) have been prepared in 50–70% yield by base-catalyzed condensation of 5,5-di-tert-butyl-2,2-dihydroxybiphenyl (1) with formaldehyde in refluxing xylene. An attempted alkylation of the flexible macrocycles2b and2c with ethyl bromoacetate in the presence of Cs₂CO₃ under acetonitrile reflux gave only one pure stereoisomer3 and4, respectively, while other possible isomers were not observed. The structural characterization of these products is also discussed. The two-phase solvent extraction data indicated that hexaethyl ester3 and octaethyl ester4 show strong metal affinity, comparable with that of the corresponding calix[n]arenes, and a high K⁺ selectivity was observed for octaethyl ester4.¹H-NMR titration of hexaethyl ester3 and octaethyl ester4 with KSCN clearly demonstrate that a 11 complex is formed which is stable on the NMR time scale.This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.     

The synthesis of imidazole-2-thione nucleosides

Ribosylation of the trimethylsilyl derivative ( 1b ) of imidazole-2-thione ( 1a ) using either stannic chloride or silver perchlorate as catalyst resulted in the formation of the acylated derivatives of 1-(β-D-ribofuranosyl)imidazole-2-thione ( 3c ) and 1,3-di-(β-D-ribofuranosyl)imidazole-2-thione ( 4c ) with the latter predominating ( 4c:3c , ca. 2:1 ). The diribosylated nucleoside 4c was shown to be the N,N-disubstituted product rather than the N,S-disubstituted product by ¹H nmr and ¹³C nmr spectroscopy. Employment of the iodine-catalyzed fusion procedure reversed the aforementioned product ratios and provided the monoriboside 3c in excellent yield. When the trimethylsilyl derivative ( 5b ) of 2-methylthioimidazole ( 5a ) was reacted with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2d ) in acetonitrile, the major product was 1,3-di-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-imidazole-2-thione ( 4b ). The formation of 4b in this reaction is thought to arise via the Hilbert-Johnson mechanism.     

Metallic Particles from Complexing Microcapsules Dispersed in a Silica Gel

A new process to control the distribution of metal nanoparticles is proposed. It involves the use of complexing microcapsules obtained by interfacial polycondensation. The latter are hollow spheres constituted of a polymer membrane, containing an insoluble active ingredient, such as a polyacrylic acid, which can complex Co²⁺ ions. These capsules are dispersed in a silica sol followed by thermal treatments and reduction under H₂ which results in metallic Co nanoparticles confined in the capsules domains. The particles do not diffuse in the matrix.     

Synthesis,stereochemistry and pharmacological activity of rac.-cis-tetrahydro-6-hydroxy-7-(4-methoxyphenyl)-1,4-thiazepin-5(2H)-ones

Reaction of 2-aminoethanethiol ( 3 ) with trans-3-(p-methoxyplienyl)glycidate ( 4 ) gave the rac.-cis-1,4-thiazepinone 5 and a by-product 6 . The structure of 5 was proven by X-ray crystallography. The X-ray data revealed that this compound adopts the chair conformation in the solid state and the heterocyclic ring is sevenmembered. The structure of the by-product 6 was elucidated on the basis of spectral data. Compounds 9 and 10 were inactive as calcium channel blocking agents.     

Modification de la position 8 des purines nucleosides et de l'adenosine monophosphate cyclique-3′,5′. Reactions de couplage catalytique des organo-magnesiens avec les bromo-8 purines ribosides et bromo-8 adenosine monophosphate cyclique-3′,5′ silyles en presence de dichloro-bis-triphenylphosphine palladium

The palladium catalysed condensation of Grignard reagents with silyl derivatives of 8-bromopurine nucleosides and 8-bromoadenosine-3′,5′ cyclic monophosphate is a convenient method for the preparation of free 8-alkylpurine nucleosides and 8-alkyladenosine-3′,5′ cyclic monophosphate.     

Optimisation and robustness analysis of a hydrophobic interaction chromatography step

Process development, optimisation and robustness analysis for chromatography separations are often entirely based on experimental work and generic knowledge. The present study proposes a method of gaining process knowledge and assisting in the robustness analysis and optimisation of a hydrophobic interaction chromatography step using a model-based approach. Factorial experimental design is common practice in industry today for robustness analysis. The method presented in this study can be used to find the critical parameter variations and serve as a basis for reducing the experimental work. In addition, the calibrated model obtained with this approach is used to find the optimal operating conditions for the chromatography column. The methodology consists of three consecutive steps. Firstly, screening experiments are performed using a factorial design. Secondly, a kinetic-dispersive model is calibrated using gradient elution and column load experiments. Finally, the model is used to find optimal operating conditions and a robustness analysis is conducted at the optimal point. The process studied in this work is the separation of polyclonal IgG from BSA using hydrophobic interaction chromatography.     

Electrodynamic investigations of conduction processes in humid microcrystalline cellulose tablets

The conduction mechanism in microcrystalline cellulose (MCC) tablets at varying relative humidity (RH) has been investigated by using the techniques of low frequency dielectric spectroscopy and transient current analysis at room temperature. The dependence on RH on the measured conductivity and charge carrier density indicates that a high-power-law-exponent percolation process of cations being conducted on water molecules occupying available 6-OH units on the cellulose chains is the dominating dc conduction mechanism at RH below 3 wt % of moisture content. The experimentally observed decrease in charge carrier mobility with increasing moisture content shows that protons and H3O+ ions that are being blocked at empty 6-OH sites also contribute to the charge transport process in cellulose at low moisture contents.     

Folic acid analogs. III. N-(2-[2-(2,4-diarnino-6-quinazolinyl)ethyl]benzoyl)-l-glutamic acid

A trideaza analog of aminopterin, N-(4[2-(2,4-diamino-6-quinazolinyl)ethyl]benzoyl)-L-glutamic acid, was prepared by a Wittig condensation of 2,4-diaminoquinazoline-6-carboxaldehyde and [P-(N-[1,3-bis(ethoxycarbonyl)propan-1-yl]aminocarbonyl)phenylmethyl]triphenylphosphonium bromide followed by catalytic reduction and mild hydrolysis. This compound was found to have confirmed inhibitory activity against leukemia L1210 in mice.     

Microwave-enhanced carbonylative generation of indanones and 3-acylaminoindanones

The development of microwave-accelerated protocols for palladium(0)-catalyzed carbonylative cyclization of unsaturated aryl bromides and chlorides is described. By employing o-bromostyryl derivatives lacking substituents on the vinylic bond, molybdenum hexacarbonyl-mediated in situ carbonylation delivered a set of indan-1-one products in high yield after only 20 min of heating. Without the addition of the tri-tert-butylphosphine releasing Fu-salt ((t-Bu)(3)PHBF(4)), only incomplete conversions of sluggish o-styryl bromides and chlorides were realized. Internal and chemoselective palladium(0)-catalyzed Heck arylations of enamides afforded suitable starting materials for subsequent rapid ring-closing reactions. Microwave-heated intramolecular in situ carbonylation of these electron-rich and sterically congested olefins conveniently afforded eight functionalized 3-acylaminoindanone derivatives in a novel synthetic process. Attempted carbonylative annulation of electron-poor o-bromocinnamic acid derivatives furnished only the corresponding lactones via a competing hydroxycarbonylation-Michael addition reaction sequence.     

51V magic angle spinning NMR spectroscopy of Keggin anions [PVnW12-nO40](3+n)-: effect of countercation and vanadium substitution on fine structure constants

Vanadium environments in Keggin oxopolytungstates were characterized by (51)V solid-state MAS NMR spectroscopy. (C(4)H(9))(4)N(+)-, K(+)-, Cs(+)-, as well as mixed Na(+)/Cs(+)- salts of the mono-, di-, and trivanadium substituted oxotungstates, [VW(11)O(40)](4-), [V(2)W(10)O(40)](5-), and [V(3)W(9)O(40)](6-), have been prepared as microcrystalline and crystalline solids. Solid-state NMR spectra report on the local environment of the vanadium site in these Keggin ions via their anisotropic quadrupolar and chemical-shielding interactions. These (51)V fine structure constants in the solid state are determined by the number of vanadium atoms present in the oxoanion core. Surprisingly, the quadrupolar anisotropy tensors do not depend to any significant extent on the nature of the countercations. On the other hand, the chemical-shielding anisotropy tensors, as well as the isotropic chemical shifts, display large variations as a function of the cationic environment. This information can be used as a probe of the local cationic environment in the vanadium-substituted Keggin solids.