bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of peptide‐morphinans based on Diels‐Alder adducts of thebaine with enkephalin moieties (chemistry of opium alkaloids, Part XVI)
Authors: Beyerman H. C. , Lie T. S. , Maat L. , Noordam‐Weissdorf M.
Published: September 2010

The preparation of Diels‐Alder adducts of (‐)‐thebaine and ethyl acrylate is described. Hydrolysis of the major adduct gave the 7α‐carboxylic acid which was coupled with the ethyl esters of L‐leucine, L‐phenylalanyl‐L‐leucine and glycyl‐L‐phenylalanyl‐L‐leucine, respectively, three peptide segments derived from the endogenous opiate, leucine‐enkephalin. These compounds, as well as the 7β‐ethoxycarbonyl isomer, were O‐demethylated to give the corresponding 3,6‐dihydro‐xymorphinan derivatives. N‐(6,14‐endo‐Etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐carbonyl)‐L‐phenylalanyl‐L‐leucine ethyl ester and its 7,8‐dihydromorphine analogue were reduced to the corresponding leucinols.

Pharmacological screening

Dr. A. E. Jacobson, National Institutes of Health, Bethesda, Maryland, U.S.A.

showed that several of these compounds are morphine‐like analgesics, notably compound 11, N‐(6,14‐endo‐etheno‐7,8‐dihydromorphine‐7α‐carbonyl)‐L‐leucine ethyl ester.
1‐Methylpyridinio and 2,4‐dinitrophenyl groups as electron acceptors in poly(iminomethylenes)
Authors: Oostveen E. A. , Drenth W.
Published: September 2010

The synthesis and charge‐transfer (CT) spectra are described for a series of homopolymers and copolymers of poly(iminomethylenes), magnified image, which contain pyridinium groups as acceptor and iodide ions as donor. The group R includes 3‐[1‐CH3‐N⊕C5H4]CH2‐(1c), 3‐[1‐CH3‐N⊕C5H4]CH(CH3)‐ (2c), 4‐[1‐CH3‐N⊕C5H4]CH(CH3)‐ (3c) and 4‐[1‐CH3‐N⊕C5H4]CH2CH2‐ (4c), I− being the counter ion. The copolymers consist of either the monomeric units of 1c and 4c [ratio 1: 1 (5c) and 1:2 (5d] or of [3−[1−[2,4−(NO2)2C6H4CH2]−N⊕C5H4]]CH(CH3)N=magnified image and C6H5CH(CH3)N=magnified image (7c), Comparison is made between the iodide to pyridinium CT spectra of 1,3‐dimethylpyridinium iodide (8) and the polymer of 4‐vinyl‐1‐methylpyridinium iodide (9). With respect to the former compound, these CT bands of the polymers 1c‐4c show a large bathochromic shift, which is largely attributed to their low microenvironment polarity. An even larger bathochromic shift was observed in the CT spectra of the copolymers 5a and 5d. This additional effect is attributed to iodide ions being intercalated between pyridinium cations. On complexing copolymer 7c with N,N,N′,N′‐tetramethyl‐1,4‐benzenediamine, complete charge transfer occurred. This phenomenon is attributed to intercalation of the diamine between two dinitrophenyl groups.
Chemistry of crown ethers XIX. Functionalized crown ethers for the solubilization of barium sulfate
Authors: de Jong F. , van Zon A. , Reinhoudt D. N. , Torny G. J. , Tomassen H. P. M.
Published: September 2010

The use of seawater as injection fluid in oil‐producing formations often leads to blocking of the wells as a result of barium sulfate‐scale formation. Macrocyclic complexants specifically designed to solubilize barium sulfate efficiently into water have been synthesized and their BaSO4‐solubilizing capacities have been determined. The stability of barium complexes of macrocyclic polyethers can be greatly increased by the introduction of flexible side‐chains containing anionic groups. Most of the newly synthesized complexants, based mainly on diaza‐18‐crown‐6, give very stable complexes. However, many of them are extremely insoluble in water. Only bis(carboxymethyl)diaza‐18‐crown‐6, bis(phosphonomethyl)diaza‐18‐crown‐6 and, to a lesser extent, bis‐(dicarboxymethyl)diaza‐18‐crown‐6 and bis[(hydroxyphosphinyl)methyl]diaza‐18‐crown‐6 are efficient solubilizers of BaSO4 in water.
The Chichibabin amination of 4‐phenyl‐ and 4‐tert‐butyl‐pyrimidine
Authors: Breuker J. , van der Plas H. C.
Published: September 2010

During a study on the amination of 4‐phenylpyrimidine in potassium amide/ liquid ammonia it was found that the extent to which the SN(ANRORC) mechanism operates in the amination largely depends upon whether an ammonium salt is used in quenching the reaction. The composition of the σ‐adduct mixture, the structure of the open‐chain intermediates, the inhibition of the SN(ANRORC) mechanism and the course of the amination in apolar solvents have been investigated. In addition, it has been found that, in the amination of 4‐tert‐butylpyrimidine, the SN(ANRORC) mechanism occurs to only a very limited extent.
Synthesis of fragments of human β‐lipotropin, βh‐LPH. Part VI. The synthesis of des‐1‐tyrosine‐α‐endorphin and shortened peptides
Authors: Bijl W. A. A. J. , van Nispen J. W. , Greven H. M.
Published: September 2010

The synthesis of des‐1‐tyrosine‐α‐endorphin and fourteen fragments of this psychostimulant type of neuropeptide is described. In these syntheses use has been made of the classical fragment condensation approach.
Selective allylation of sugar derivatives containing the 1,1,3,3‐tetraisopropyldisiloxane‐1,3‐diyl protective group
Authors: Oltvoort J. J. , Kloosterman M. , van Boom J. H.
Published: September 2010

Using the method of Guibe et al. we were able to selectively introduce an allyl group at the 2‐position in methyl‐4,6‐O‐(tetraisopropyldisiloxane‐1,3‐diyl)‐α‐D‐glucopyranoside and benzyl‐4,6‐O‐(tetraisopropyldisiloxane‐1,3‐diyl)‐β‐D‐glucopyranoside. The dynamic properties of the tetraisopropyldisiloxane‐1,3‐diyl protective group gave us access to a glucose derivative which carried a 1‐propenyl group at the 2‐position, an allyl group at the 6‐position and a tetraisopropyldisiloxane‐1,3‐diyl at the 3,4‐position together with a glucose derivative protected with an allyl, an acetyl and a 3‐hydroxytetraisopropyldisiloxanyl at the 2‐, 3‐ and 4‐positions, respectively.
Cycloaddition of (dimethylamino)allene to some electrophilic alkenes and its application to the synthesis of 3‐alkylidenecyclobutenes
Authors: Klop W. , Klusener P. A. A. , Brandsma L.
Published: September 2010

(Dimethylamino)allene and electrophilic alkenes react under mild conditions to give [2 + 2]‐ and [2 + 4]‐cycloadducts in excellent yields. Conversion of the amino group in the [2 + 2]‐adducts into quaternary salts, followed by elimination of tertiary amine and hydrogen halide, under the influence of l,8‐diazabicyclo[5. 4. 0]undec‐7‐ene (DBU) in hexamethylphosphoric triamide (HMPT), affords 3‐alkylidenecyclobutenes in high yields.
Characterization of a glassy‐carbon‐electrode surface pretreated with rf‐plasma
Authors: Schreurs J. , van den Berg J. , Wonders A. , Barendrecht E.
Published: September 2010

The composition of oxidic groups at a glassy‐carbon surface has been studied using phase‐sensitive ac‐voltammetry. Two types of quinones have been identified, i.e. the 1, 2‐naphtoquinone‐ and the 9, 10‐phenanthrenequinone‐like structures. The 1, 4‐naphtoquinone‐ and 9, 10‐anthraquinone‐like structures are, most probably, also present at the glassy‐carbon surface, although in lower surface concentrations. The o‐quinones can be converted into the corresponding benzophenazines (by reaction with o‐phenylenediamine), which are also electroactive. The differences in redox potentials between the quinones and phenazines make detection of intermediate reaction stages possible. The effect of oxygen and argon rf‐plasma treatment upon the composition of the quinone‐surface groups has also been studied. Pretreatment of the glassy‐carbon surface by an oxygen rf‐plasma is a very powerful and clean oxidation technique. Argon rf‐plasma increases the 9, 10‐phenanthrenequinone‐like structures, while oxygen rf‐plasma, with successive cooling in an argon atmosphere, diminishes the surface concentration of quinone structures and increases that of the acidic surface groups, as can be concluded from modification experiments. From phase‐sensitive ac‐voltammetry measurements, a lower limit of 103 s−1 was determined for both the quinone and the phenazine surface reaction rate constants (ks).
The structure of cis‐platinum trinucleoside diphosphate species; the influence of ligand substitutions upon the conformation of the adducts
Authors: den Hartog Jeroen H. J. , Altona Cornelis , van Boom Jacques H. , Reedijk Jan
Published: September 2010

The conformations of the trinucleoside diphosphates in cis‐Pt(LL)[d(GpCpG)‐N7(1), N7(3)] complexes have been studied with LL = (NH3)2 1, cyclohexane‐1, 1‐bis(methanamine) (chbma) 2, 1, 2‐ethanediamine (en) 3, or N, N, N′ N′ ‐tetramethyl‐1, 2‐ethanediamine (tmen) 4. The 1H NMR chemical shifts, together with the conformational equilibria in the sugar rings and the nuclear Overhauser enhancements, have been studied as a probe for structural changes. It appears that the structure of the oligonucleotide part of the molecule is to a large extent the same in 1, 2 and 3. In contrast, the tmen ligand induces relatively large chemical‐shift changes in 4 with respect to 1, 2 and 3. It is suggested that this behaviour is caused by a retarded rotation about the Pt – N7 bonds, giving rise to a more rigid, preferred conformer in the case of 4. The conformational freedom observed in compounds 1, 2 and 3 is indicative of fast rotation on the NMR time scale along the Pt‐N7 bonds and thus of a “head‐to‐tail” arrangement around the platinum atom.
An investigation of the electronic structure of α, β‐unsaturated acetylamino acid ethyl esters using He(I) and He(II) photoelectron spectroscopy
Authors: Ajò D. , Casarin M. , Granozzi G. , Ottenheijm H. C. J. , Plate R.
Published: September 2010

The He(I)‐ and He(II)‐excited photoelectron spectra of the ethyl esters of α, β‐unsaturated acetylamino acids (1a–4a) are presented and discussed. The spectra are assigned by comparison with those of related molecules and by analysis of the relative band intensities under different radiation sources. The effects of β‐substitution on the electronic structure and conformation are also discussed.
Nouvelles synthèses de systèmes bihétérocycliques II. Cycloaddition dipolaire‐1,3 et condensation de carbène sur des triazépines‐1,2,4
Authors: Hasnaoui A. , El Messaoudi M. , Lavergne J.‐P.
Published: September 2010

The condensation of mesitonitrile and dichlorocarbene in aqueous medium to 1,2,4‐triazepines has been studied. In all cases this cycloaddition is peri and regiospecific. Compounds with the unknown ring systems isoxazolo[5,4‐e]‐1,2,4‐triazepine and azirino[2,1‐g]‐1,2,4‐triazepine have been synthesized. The structural elucidation of these products was accomplished by spectral evidences.
The chemistry of small‐ring compounds. Part 48. Oxidation of cyclopropylidenecycloalkanes with singlet oxygen
Authors: van den Heuvel C. J. M. , Steinberg H. , de Boer Th. J.
Published: September 2010

Cyclopropylidenecyclohexane undergoes the ene reaction with singlet oxygen. The migrating allylic hydrogen originates exclusively from the cyclohexane ring and therefore the hydroperoxy group becomes attached to the cyclopropane ring. Since the O ‐ O bond in cyclopropyl peroxy systems is weak, the reaction product undergoes homolysis even at − 50°C and this also triggers rupture of the small ring.

The resulting radical pair, consisting of 7 and the hydroxyl radical, recombines to form unsaturated β‐hydroxy ketone 8 and the di‐α, β‐unsaturated ketone 9 (cf. Scheme 2).

As a model for a cyclopropylidenecycloalkane containing no active allylic hydrogen, the adamantyl derivative 10 was subjected to photo‐oxidation. In this case, the product is lactone 11 (yields in Table I), formed by early ring enlargement, i.e. before O ‐ O rupture, as outlined in Scheme 4.

The zwitter ion 15a isomerises to the key intermediate carbonyl oxide 17 and, as a result of the presence of the cyclobutane ring, this can rearrange to lactone 11 in various ways (cf. Scheme 5 and 6). By photo‐oxygenation in 18O‐labelled acetone, zwitter ion 17 is trapped by the solvent as an unstable ozonide which decomposes with formation of 18O‐labelled lactone (Scheme 7). Photo‐oxygenation in the presence of TCNE gives exclusively ketone 12 by deoxygenation of 17 (Scheme 4).
Mechanistic photochemical studies on the 1,3‐acyl shift and oxa‐di‐π‐methane rearrangement of two β,γ·γ′,δ′‐dienones
Authors: Koppes Margareth J. C. M. , Cerfontain Hans
Published: September 2010

The photochemical rearrangement of the two 2‐(2‐alkenyl)‐2‐(1‐cyclopentenyl)cyclopentanones (E)‐1aand (E)‐2ahave been studied under conditions of both direct (λ 300 nm) and tripletsensitized irradiation in order to determine the applicability of 2‐alkenyl moieties as intramolecular quenchers of the lowest excited triplet states of the β,γ‐enone chromophore.

The β,γ·γ′,δ′‐dienone (E)‐1a, upon direct irradiation, exhibits a reversible 1,3‐acyl shift (1,3‐AS) leading to an eventual photostationary state {[(E)‐1a]/[(E)‐1b]}pss= 4.0 ± 0.8, whereas triplet photosensitization of (E)‐1agives the ODPM isomer (E)‐1c. Both processes occur without (E)‐(Z) isomerization of the 2‐butenyl side‐chain. Direct irradiation of (E)‐2ayields, albeit very inefficiently, the 1,3‐AS compound (E)‐2b(Φ < 0.001) as the primary product which, upon electronic excitation, forms, in competing reactions, (E)‐2a(Φ = 0.18) and (Z)‐2b(Φ = 0.035). Upon triplet photosensitization of both (E)‐2aand (E)‐2b, only (E)‐(Z) isomerization of the styryl side‐chain is observed. The eventual photostationary state in the direct irradiation equals {[(E)‐2a]/[(Z)‐2a]/[(E)‐2b]/[(Z)‐2b]}pss=(33± 1)/(33 ± 1)/(17 ± 1)/(17 ± 1).

The differences in photochemical behaviour of the β,γ·γ′,δ′‐dienone substrates and their 1,3‐AS products are discussed with special emphasis being placed upon the triplet energies of the 2‐alkenyl chromophores relative to those of the β,γ‐enone chromophores and the occurrence of CT interaction which enhances the internal conversion of theS1(nπ*) states of the β,γ‐enone chromophores.
Photochemical synthesis of 5‐alkylpyrimidine nucleosides
Authors: Hassan Mohamed E.
Published: September 2010

5‐Alkylpyrimidine nucleosides, bearing different functional groups attached to the newly formed carbon chains at C‐5, were synthesized via a photocoupling reaction. 5‐(2‐Hydroxyethyl)uridine and its derivatives were obtained from the reaction of uridine (U) or 2′‐deoxyuridine (DU) with 2‐iodoethanol. Trimethylsilyl derivatives of 5‐iodouridine (IU) and 5‐iodo‐2′‐deoxyuridine (IDU), when treated with methyl acrylate, gave methyl 3‐(5‐uridinyl)propenoate and methyl 3‐(2′‐deoxy‐5–uridinyl) propenoate, respectively, which, upon catalytic hydrogenation, afforded 5‐[2‐(methoxy‐carbonyl)ethyl]uridine and its 2‐deoxyuridine analogue. IU and IDU also gave 5‐(2‐cyano‐ethenyl(uridine and its 2′‐deoxyuridine analogue, when treated with acrylonitrile. The latter compounds gave the corresponding 5‐(2‐cyanoethyl) nucleosides when subjected to catalytic hydrogenation.
Synthesis and properties of nitro derivatives of 2‐tert‐butyl‐ and 2,7‐di‐tert‐butylpyrene
Authors: Rodenburg L. , Brandsma R. , Tintel C. , van Thuijl J. , Lugtenburg J. , Cornelisse J.
Published: September 2010

Nitration of 2‐tert‐butyl‐ and 2,7‐di‐tert‐butylpyrene affords molecules with severely hindered nitro groups. A nitro group ortho to a tert‐butyl group is twisted at least 82° out of the plane of the aromatic nucleus. The lack of interaction between the hindered nitro group and the aromatic system is reflected in the chemical behaviour, as well as in the spectroscopic properties, of these nitro derivatives.

Upon fragmentation in the mass spectrometer, the tert‐butyl group is always replaced by a hydrogen atom. Nitro groups are only replaced by a hydrogen atom if they are ortho to a tert‐butyl group.
Synthesis of the mirror image of the RNA fragment D‐CAAGG: A model compound to study interactions between oligonucleotides of opposite handedness
Authors: Visser G. M. , van Westrenen J. , van Boom J. H. , van Boeckel C. A. A.
Published: September 2010

The pentamer L‐CAAGG was prepared starting from properly protected β‐L‐ribonucleosides via a phosphotriester approach. The identity and chiral purity of the pentamer were established by 1H NMR and CD spectroscopy, respectively.
Conformational analysis of synthetic heparin‐like oligosaccharides containing α‐L‐idopyranosyluronic acid
Authors: van Boeckel C. A. A. , van Aelst S. F. , Wagenaars G. N. , Mellema J.‐R. , Paulsen H. , Peters T. , Pollex A. , Sinnwell V.
Published: September 2010

High‐field NMR spectroscopy of synthetic heparin‐like di‐ and trisaccharides has afforded a complete set of inter‐proton‐coupling data on α‐L‐idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α‐L‐iduronic acid may display considerable conformational freedom including 1C4, 4C1 and 2S0 (e.g. compound 1) conformers.

The 2‐O‐sulphate substituent at iduronic acid tends to stabilize the 1C4 conformation (e.g. compounds 2 and 4). In addition carbohydrate substituents at position 4 hinder the 4C1 conformation (e.g. compound 3a,b versus 1).

Furthermore, the conformation of α‐L‐idopyranosyluronic acid 2‐sulphate is affected seriously by the substituent at position 2 of the non‐reducing glucosamine residue. Thus the presence of an ammonium group (i.e. compound 7) leads to unexpected deformation of the 1C4 form of iduronic acid, whereas a sulphamino substituent at this position (e.g. compound 5a,b) brings about the 2S0 skew boat conformation.

The iduronic acid moiety of a trisaccharide (compound 6), which represents a part of the anti‐thrombin III‐binding site of heparin, shows conformational preference for the 2S0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength (e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1C4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT‐III protein upon heparin binding.

Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo‐anomeric effect and Van der Waals interactions have been taken into account.
Synthesis and conformational analysis of an analogue of the antithrombin‐binding region of heparin: The role of the carboxylate function of α‐L‐idopyranuronate
Authors: van Boeckel C. A. A. , Lucas H. , van Aelst S. F. , van den Nieuwenhof M. W. P. , Wagenaars G. N. , Mellema J.‐R.
Published: September 2010

An analogue of the antithrombin‐III‐binding region of heparin has been synthesized. This analogue [GlcNSO3 (6‐OSO3)‐GlcU‐GlcNSO3 (3,6‐OSO3)‐Xyl(2‐OSO3)‐GlcNSO3 (6‐OSO3), i.e. compound 11] lacks the carboxylate function of the α‐L‐iduronic acid moiety, which implies that the 2‐O‐sulphated α‐L‐idopyranuronate unit is replaced by 2‐O‐sulphated β‐D‐xylopyranose. Compound 11 was prepared from fully protected pentasaccharide 10a, which was synthesized from two disaccharides (7 and 6b) and a monosaccharide (9). Synthesis of disaccharide 6b required preparation of a new, suitably protected xylopyranose‐building block: 2‐O‐acetyl‐ or 2‐O‐benzoyl‐3‐O‐benzyl‐4‐O‐levulinoyl‐α‐D‐xylopyranosyl fluoride 4a,b.

High‐field NMR spectroscopy of compound 11 afforded a complete set of interproton coupling data and Nuclear Overhauser Enhancement data, which have been used for conformational analysis. It appears that β‐D‐xylopyranose in compound 11 adopts exclusively the 4C1 conformation, whereas it is known that α‐L‐idopyranuronate in the naturally occurring heparin fragment exhibits 2S0 and 1C4 conformations. Thus, the carboxylate function of α‐L‐idopyranuronate in the heparin fragment is an important conformational drive.

Since neither compound 11 nor another analogue containing L‐idose (with similar conformational properties as the natural fragment) elicit AT‐III‐mediated activity, it is proposed that the carboxylate of idopyranuronate interacts with AT‐III to bring about the active conformation of the protease inhibitor.
Conformational analysis of three simple organosilicon compounds
Authors: Jenneskens Leonardus W. , Louwen Jaap N. , van den Berg Ellen M. M. , van Beuzekom Aart A. , Lugtenburg Johan
Published: September 2010

The 1H NMR spectra of 3‐(triethoxysilyl)propanenitrile (1), 3‐(trichlorosilyl)propanenitrile (2) and trichloropropylsilane (3) show that these systems are present to about 40% in the gauche conformer. For 1 and 3, the solvent dependence of the conformational equilibrium has also been studied. In more polar solvents, the more polar gauche conformers contribute to a greater extent to the equilibrium mixture. The results of MNDO calculations for these compounds are compared with the conclusions drawn from the NMRz measurements. The reliability of MNDO for the description of this type of organosilicon compound is described.
Mechanistic studies of the oxidative‐coupling polymerization of 2,6‐dimethylphenol. Part V: Effect of different copper counter‐ions on the structure of the copper complex, its catalytic activity and specificity for polymer formation
Authors: Viersen F. J. , Challa G. , Reedijk J.
Published: September 2010

In studying the mechanism of the oxidation coupling polymerization of 2,6‐dimethylphenol, the effect of the copper counter‐ion was also investigated. This polymerization is catalyzed by copper(II)‐amine complexes. In these experiments, tmed*** is used as amine ligand. The counter‐ions were divided into strongly coordinating (viz. Cl− and Br−), weakly coordinating (viz. NO3−) and non‐coordinating counter‐ions (viz. ClO4−, CF3SO3− and BF4−).

Catalyst solutions, prepared from copper salts with coordinating counter‐ions, yield very high maximum activities at OH/Cu ≈︁ 1, whereas the non‐coordinating counter‐ions give much lower maximum reaction rates at OH/Cu ≈︁ 2 or higher. Copper‐amine complexes of weakly and non‐coordinating counter‐ions were found to yield hydroxo‐bridged complexes with a very low catalytic activity under all conditions. Due to this stable dihydroxo bridge and the absence of coordinating counter‐ions (Cl−, Br−) to replace them, only phenolate anion can readily attack this complex and occupy a coordination site at the expense of a coordinated OH− ion, thus explaining the optimum activity at an OH/Cu ratio of 2 or higher. However, even under these conditions, catalytic activity of these complexes is still low compared to catalysts prepared from CuCl2 or CuBr2, further suggesting that preformation of a chloro‐bridged or bromo‐bridged copper complex is beneficial. Thus, these experiments indicate that the active catalyst, or its precursor, is the chloro‐bridged, or bromo‐bridged, dinuclear copper complex with hydroxide acting as a co‐catalyst required for the formation of strongly coordinating phenolate anions.

Although large differences in reactivity were observed, the product composition, i.e. the fraction polymer (by C‐O coupling) and diphenoquinone (DPQ, undesired side‐product formed by C‐C coupling), was not affected by the counter‐ion used, viz. 3.5% DPQ. These results are a further indication that specificity is not primarily determined by the catalyst structure.
Thermally Stable Arylpalladium Diamine Complexes as Versatile Precursors in Organopalladium Chemistry; Synthesis and X‐Ray Molecular Structure of PdIPh(tmeda) and its Conversion to PdMePh(tmeda) {tmeda = Me2N(CH2)2NMe2}
Authors: de Graaf Wim , van Wegen John , Boersma Jaap , van Koten Gerard , Spek Anthony L.
Published: September 2010

The new complex PdIPh(tmeda) (1) (tmeda = Me2N(CH2)2NMe2) was prepared by oxidative addition of iodobenzene to {bis(dibenzylideneacetone)}palladium(0) in the presence of tmeda and has been characterized by NMR spectroscopy and X‐ray crystallography. Treatment with MeLi affords the remarkably stable mixed diorgano species PdMePh(tmeda) (2). Both (1) and (2) are useful precursors to other organopalladium species by ligand exchange reactions.
Chemisorption and catalysis of zeolite‐entrapped palladium
Authors: Homeyer S. T. , Karpiński Z. , Sachtler W. M. H.
Published: September 2010

The chemisorption of H2and of CO and the catalysis of neopentane conversion have been studied on two groups of Y‐zeolite‐supported Pd samples. One group was prepared under conditions which result in the formation of “grape‐shaped” Pd particles filling adjacent supercages. In the second group, pretreatment conditions were chosen which yield isolated Pd particles of the size of the supercages. Both groups of Pd/NaY samples differ in adsorption of H2and CO; the COads/Hadsratios are in agreement with the different particle morphologies. The selectivity of neopentane conversion does not detectable depend on Pd morphology; however, the activation energy for reaction is significantly higher for the samples of the first group.
Preparation of optically pure 2‐aryl‐ and 2‐aryloxy‐propionates by selective enzymatic hydrolysis
Authors: Mutsaers J. H. G. M. , Kooreman H. J.
Published: September 2010

Selective enzymatic hydrolysis of racemic esters is an attractive method for the resolution of 2‐aryl‐ and 2‐aryloxy‐propionates. The non‐steroidal antiinflammatory drugs, naproxen, ibuprofen, flurbiprofen and the herbicides, fluazifop and diclofop, can be obtained in high optical purity with the aid of carboxylesterase NP. This enzyme was brought to high production levels by cloning it into Bacillus subtilis 1‐85. The unfavourable influence of a non‐specific lipase, present in the wild type rain, was also completely eliminated by cloning. The ability of the esterase under application conditions was greatly improved by chemical modification, the be results being obtained with formaldehyde, glutaraldehyde and glyoxal.
Biocatalytic production of hydroxylated aromatic and alicyclic compounds: Products derived from tetralin
Authors: Sikkema Jan , de Bont Jan A. M.
Published: September 2010

Biological hydroxylation is an area with many opportunities for the production of fine chemicals. Especially for the production of hydroxylated aromatic and alicyclic compounds, the specificity and mildness of biocatalysis can be beneficial. 1,2,3,4‐Tetrahydronaphthalene (Tetralin) is a bicyclic aromatic compound, consisting of an aromatic and an alicyclic moiety. The biological oxidation of this compound provides an interesting model reaction, because different sites of initial attack are possible. Eight rains of bacteria that utilize tetralin as sole source of carbon and energy have been teed for the formation and accumulation of interesting oxidation products. Accumulation of oxidation products characteristic of both the oxidation of the aromatic and the alicyclic moiety has been demonstrated. Two rains, aCorynebacteriumand anAcinetobacterhave been studied in more detail.CorynebacteriumC125 starts with initial attack on the aromatic ring by a dioxygenase type of enzyme resulting in the formation of acis‐dihydro diol that is chemically dehydrated to a phenol in an acid environment.AcinetobacterT5 starts with oxidation of the benzylic carbon atom, resulting in the formation of an alcohol, that is further oxidized via a ketone.
Molecular recognition of neutral molecules by rigid binaphthyl metalloclefts: Synthesis, complexation and calculations
Authors: van Doorn Arie R. , Rushton David J. , Verboom Willem , Reinhoudt David N. , Bos Marinus
Published: September 2010

The binaphthyl metallocleft 2 in which an electrophilic uranyl cation is immobilized was synthesized by reaction of 1,2‐benzenediamine and aldehyde 5. According to 1H‐NMR spectroscopy, 2 is formed as a mixture of meso and racemic diastereomers (ratio 1:0.85). The complexation of 2 with pyridine, (iso)quinoline, acridine, benzylamine, and 1‐naphthalenemethanamine was investigated. The association constants of the complexes with aromatic amines vary from 3.5 · 102 to 3.6 · 106 M−1 (meso‐2) and 1.5 · 102 to 1.0 · 106 M−1 (racemic‐2). The higher stability of the complexes with meso‐2 is in agreement with the results of molecular mechanics calculations.
Chemical modification of azasugars, inhibitors of N‐glycoprotein‐processing glycosidases and of HIV‐I infection: Review and structure‐activity relationships
Authors: van den Broek L. A. G. M. , Vermaas D. J. , Heskamp B. M. , van Boeckel C. A. A. , Tan M. C. A. A. , Bolscher J. G. M. , Ploegh H. L. , van Kemenade F. J. , de Goede R. E. Y. , Miedema F.
Published: September 2010

The synthesis of a series of analogues of the α‐glucosidase inhibitor 1‐deoxynojirimycin (dNM, 1) and of the α‐mannosidase inhibitor 1‐deoxymannojirimycin (dMM, 3) is described. The ability of dNM, dMM and a series of N‐alkylated dNM and dMM derivatives to interfere with biosynthesis, transport and maturation of the glycoprotein α1‐antitrypsin in human hepatoma HepG2 cells and with the syncytium‐inducing capacity of HIV‐infected cells was investigated. A strong correlation was observed between α‐glucosidase inhibition found in HepG2 cells and antiviral activity in HIV‐I‐infected cells. N‐Butyl‐ (35), N‐pentyl‐ (38), N‐benzyl‐ (41) and N‐decyl‐dNM (47) showed high activity in both assays. N‐Decyl‐dNM was active at 0.01 mM but showed drug‐related cell toxicity at concentrations exceeding 0.1 mM. Branching of the N‐alkyl side chain reduced the activity of dNM derivatives considerably. N‐Benzyl‐6‐O‐butyryl‐dNM (42) and N‐decyl‐6‐O‐benzoyl‐dNM (48) showed activity comparable to that of N‐benzyl‐dNM (41) and N‐decyl‐dNM (47), respectively. None of the dMM analogues prevented HIV‐induced syncytia formation. The 3‐hydroxyl group in dNM and in dMM plays a crucial role in the interaction of these drugs with the corresponding processing glycosidases: 3‐O‐methyl‐dNM (49) and 3‐O‐methyl‐dMM (56) were inactive in both assays. The plasma membrane constitutes a permeability barrier for castanospermine (CAS, 2), but not for dNM, since the activity of CAS in streptolysin‐O‐permeabilized HepG2 cells was significantly higher than that in intact HepG2 cells. Finally, an overview is given of structures, other than the many N‐substituted derivatives that were described, related to dNM and dMM that have appeared in the literature in recent years.
Synthesis and characterization of isotopically labelled drugs
Authors: Kaspersen Frans M. , Vader Jan F. , Funke Carel W. , Sperling Eric M. G.
Published: September 2010

The article describes approaches for the synthesis and analysis of isotopically (2H,3H,13C,14C,35S) labelled drugs necessary for the development of a pharmacologically active compound into a registered drug.

Special features such as isotope effects, radiolysis and3H NMR spectra are discussed.
The synthesis and properties of some long‐chain alkyl‐D‐glucofuranosidurono‐6,3‐lactones, D‐glucofuranosides and derivatives thereof
Authors: Raaijmakers Harry W. C. , Zwanenburg Binne , Chittenden Gordon J. F.
Published: September 2010

Several long‐chain alkyl‐D‐glucofuranosidurono‐6,3‐lactones were synthesized by the acid‐catalysed glycosidation of glucurono‐6,3‐lactone. The alkyl β‐D‐glucofuranosidurono‐6,3‐lactones were reacted with sodium borohydride to give the corresponding alkyl β‐D‐glucofuranosides, and with 2‐aminoethanol andN,N‐dimethylethanediamine to give the corresponding alkyl‐N‐(2‐hydroxyethyl)‐β‐D‐glucofuranosiduronamides and alkyl‐N‐[2‐(dimethylamino)ethyl]‐β‐D‐glucofuranosiduronamides, respectively. The dodecyl‐N‐[2‐(dimethylamino)ethyl]‐β‐D‐glucofuranosiduronamides were quaternized with iodomethane to give the ammonium iodides. These new compounds, and some representative derivatives, were characterised by1H‐ and13C‐NMR spectroscopy. The physical properties (liquid‐crystal behaviour, surface tension, CMC) of some of these compounds were also determined.
Steroid cyclophanes as artificial receptors embedded in synthetic bilayer membranes: Aggregation behavior and molecular recognition
Authors: Murakami Yukito , Kikuchi Jun‐Ichi , Inada Masahiko , Miura Hideaki , Suehiro Kazuaki , Hayashida Osamu
Published: September 2010

Two steroid cyclophanes, having individually L‐lysine and L‐aspartate residues as connector units interposed between a 1,6,20,25‐tetraaza[6.1.6.1]paracylophane skeleton and four cholate moieties, were designed and synthesized. The cationic steroid cyclophane, having L‐lysine residues, binds anionic and non‐ionic guests very efficiently, while it has no capacity to bind a guest with a positive charge in aqueous solution. On the other hand, the anionic steroid cyclophane, bearing L‐aspartate residues, shows good binding affinity toward hydrophobic guests in aqueous solution regardless of their charged states. Aggregate morphology of the cationic and anionic peptide lipids, involving an L‐alanine residue interposed between a charged head moiety and a hydrophobic double‐chain segment, in the sonicated vesicular state was not perturbed significantly upon formation of hybrid assemblies with the steroid cyclophanes in 2.5 mol%. Even though the anionic bilayer vesicle interacts only weakly with anionic guests, the corresponding hybrid assembly formed with the cationic steroid cyclophane is capable of marked molecular recognition of anionic guests, along with shape‐sensitive discrimination, through electrostatic and hydrophobic interactions in aqueous solution. In a similar manner, the cationic bilayer membrane alone is incapable of binding a cationic guest. However, the guest‐binding ability is not much enhanced in the presence of the anionic steroid cyclophane. Consequently, the cationic steroid cyclophane can act as an efficient cell‐surface receptor model for anionic guests while the anionic steroid cyclophane is not a good receptor model when both are embedded in bilayer membranes.
Application of the Mitsunobu reaction to ephedrines and some related amino alcohols. Aspects of intramolecular participation of the amino group
Authors: Poelert Martin A. , Kellogg Richard M. , Hulshof L. A.
Published: September 2010

Inversion of configuration at the benzylic hydroxyl group of (1S,2S)‐pseudoephedrine (2) to afford (1R,2S)‐ephedrine is known to be a difficult process. The Mitsunobu reactions of 1 and 2 might offer a route to achieve such inversions. In fact Mitsunobu reactions on 1 and 2 are known to proceed via aziridines formed on intramolecular SN2 substitution by the amine functionality. The Mitsunobu reactions of N‐methylated and N‐benzylated ephedrines have been found to proceed via the corresponding aziridinium ions. These aziridinium ions can be opened (SN2 substitution) by nucleophiles like phthalimide and thiols. Intramolecular participation in 2 can be avoided by use of the tert‐butyloxycarbonyl‐ (BOC) or benzyloxycarbonyl‐ (CBZ) protected derivatives. Mitsunobu reactions on these derivatives lead to inversion of configuration at the benzylic hydroxyl center. In contrast the BOC and CBZ derivatives of 1 are deprotected under Mitsunobu conditions. The Mitsunobu reactions of threo (1S,2,S)‐2‐amino‐1,3‐propanediol have also been examined. An attempt to achieve protection by reaction with dimethylformamide dimethyl acetal led to the more substituted 2‐oxazoline as established by X‐ray crystallography. The desired inversion of configuration of the benzylic hydroxylic group was eventually achieved by protection of the amino substituent as the phthalimide and protection of the primary hydroxyl group as the tosylate.
Enantiomer separation of chiral inhalation anesthetics (enflurane, isoflurane and desflurane) by gas chromatography on a γ‐cyclodextrin derivative
Authors: Schurig Volker , Grosenick Heiko , Juza Markus
Published: September 2010

The preparative enantiomer separation of the inhalation anesthetics enflurane (1), isoflurane (2) and, for the first time, desflurane (3) in high chemical and enantiomeric purity by preparative gas chromatography on octakis(3‐O‐butanoyl‐2,6‐di‐O‐pentyl)‐γ‐cyclodextrin (4) dissolved in SE‐54 and coated on Chromosorb P (AW‐DMCS) is described. Thermodynamic data for the observed enantioselectivities are reported. A discrepancy between the chiroptical and gas‐chromatographic assignment of the relative configuration of2and3is discussed. The1H‐ and19F‐NMR spectra of racemic1in the presence of4show good separation of the resonances of the enantiomers of1. Thermodynamic complexation constants derived from the1H‐NMR spectra of the complexes formed by4and the enantiomers of1were in good agreement with those obtained by GC.
Solid support synthesis of a PNA‐DNA hybrid
Authors: van der Laan A. C. , Meeuwenoord N. J. , Kuyl‐Yeheskiely E. , Oosting R. S. , Brands R. , van Boom J. H.
Published: September 2010

The solid support synthesis of a homothymine PNA‐DNA octamer (i.e. hybrid 13) could be realized using tetrabutylammonium N‐(2‐(4‐methoxytrityl)‐aminoethyl)‐N‐((thymin‐1‐yl)acetyl)glycinate as PNA building block and the respective 2‐cyanoethyl‐N,N‐diisopropylphosphoramidite derivatives of both 5′‐O‐(4,4′‐dimethoxytrityl)thymidine and 5′‐N‐(4‐methoxytrityl)amino‐5′‐deoxythymidine.
Nanogel engineering for new nanobiomaterials: from chaperoning engineering to biomedical applications
Authors: Sasaki Yoshihiro , Akiyoshi Kazunari
Published: September 2010

Nanosize hydrogels (nanogels) are polymer nanoparticles with three‐dimensional networks, formed by chemical and/or physical cross‐linking of polymer chains. Recently, various nanogels have been designed, with a particular focus on biomedical applications. In this review, we describe recent progress in the synthesis of nanogels and nanogel‐integrated hydrogels (nanogel cross‐linked gels) for drug‐delivery systems (DDS), regenerative medicine, and bioimaging. We also discuss chaperone‐like functions of physical cross‐linking nanogel (chaperoning engineering) and organic‐inorganic hybrid nanogels. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Published online in Wiley InterScience (www.interscience.wiley.com)DOI 10.1002/tcr.201000008
Chlorophenol stress affects aromatic amino acid biosynthesis—a genome‐wide study
Authors: Yadav Vikas , Shitiz Kirti , Pandey Rishi , Yadav Jyoti
Published: September 2010

Chlorophenols are a class of chemicals commonly used in preservatives, disinfectants, algaecides, herbicides and pesticides. However, there is a growing evidence that these compounds are a threat to human health. This is alarming as many chlorophenols are common pollutants found in the global environment at potentially biohazardous levels. Despite chlorophenols being abundant, widely used and poisonous, we know relatively little about their mechanism of toxicity in eukaryotes. Thus, we performed genome‐wide growth screens usingSaccharomyces cerevisiaeto understand the molecular basis of chlorophenol toxicity. Of ∼4850 single gene knockout strains tested, 393 mutants showed growth sensitivity to treatment with 4‐chlorophenol (4‐CP), 2,4‐dichlorophenol (2,4‐DCP) or pentachlorophenol (PCP). Only eight mutants showed growth hypersensitivity to all the three treatments and harboured deletions in genes important for aromatic amino acid biosynthesis (ARO1, ARO7) or mitochondrial protein synthesis and respiration (ATP5, ISA1, RML2, GET2, SLS1, MRPL38). Copyright © 2010 John Wiley & Sons, Ltd.
Is it True that Injecting Palmar Finger Skin Hurts more than Dorsal Skin? New Level 1 Evidence
Authors: Wheelock Margaret E. , LeBlanc Martin , Chung Bryan , Williams Jason , Lalonde Donald H.
Published: September 2010

Background

Since the first texts on local anesthesia were written in the early 1900s, it has been widely quoted and believed that dorsal finger skin is less sensitive to needlestick pain than volar finger skin. The result is that the most commonly used finger block for local anesthesia is the dorsal two injection technique.

Methods

In this study, the needlestick discomfort associated with dorsal and volar finger skin was compared in a group of 78 volunteers who had the long finger of both hands poked with a 25 G needle; one in the midline of the volar side and the other in the lateral web space of the dorsal side. Volunteers then completed a pain scale for each needlestick and ranked which technique they would prefer for future injections.

Results

We found that there was no significant difference in needlestick pain or preference of future needle location between the dorsal and volar aspects of the finger.

Conclusions

We provide level 1 evidence that the needlestick of the SIMPLE block which has one needlestick on the volar side of the finger is not more painful than the needlestick of the dorsal finger block.
Gorham–Stout Disease Affecting Both Hands: Stabilisation during Biphosphonate Treatment
Authors: Silva Santiago
Published: September 2010

The Gorham–Stout syndrome is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report a patient with osteolysis of the metacarpal bones in both hands due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy with bisphosphonates may prevent local progressive osteolysis.
A life course approach: research orientations and future challenges
Authors: Heikkinen Eino
Published: September 2010

The need to study lifelong changes in health and functioning has resulted in increasing emphasis on a life course approach in different fields of inquiry. The aim of this approach is to explore how biological, psychological, and social risk factor trajectories, acting across the entire life course, influence age-related diseases, functional decline, and disability. The importance of the first years of life upon later development and adult characteristics was generally recognized already in the first half of the twentieth century, but it was not until the 1990s that different strands of medical and social research converge in the field of life course epidemiology, in which epidemiological processes are approached using different models such as biological programming, critical periods, pathways, and accumulation. The biological programming model holds that organ development in utero and early infancy determines the maximum functional capacity that an individual can attain and influences the development of certain chronic diseases later in life. The critical period model extends the idea to include child development and key social transitions over the entire life course. The pathway model focuses on the cumulative effect of life events along the developmental trajectories, with early advantage or disadvantage setting a person on a pathway to a later etiologically important exposure. The accumulation model describes the underlying social, behavioral, and biological processes that drive the impact of the life course on health. The growing focus on life course determinants of aging also has implications for studies of long-term changes in physical activity and their role in determining both gains and losses of health and functioning with aging. A life course approach presents great challenges for the continued development of testable theoretical models and effective study design and analysis.
Secondary immunodeficiency (immune paralysis) following spinal cord injury
Authors: Brommer B. , Kopp M.A. , Laginha I. , Schwab J.M.
Published: September 2010

Infections are a leading cause of morbidi­ty and mortality in patients with acute spinal cord injury (SCI). It has recently become clear that SCI might increase susceptibility to infec­tion by central nervous system (CNS)-specific mechanisms: CNS injury induces a disrup­tion of the normally well-balanced interplay between the immune system and the CNS. As a result, SCI also leads to secondary im­munodeficiency (SCI injury-induced immu­nodepression, SCI-IDS) and infection. SCI-IDS (a) starts early after SCI (within 24 h), (b) af­fects both the innate and adaptive immune system, and (c) is independent of iatrogenic application of high-dose corticosteroids. The fact that increased immunosuppression cor­relates with lesion level underlines a neurogenic origin. Here we summarize the current understanding and main pathophysiological features of leukocyte dysfunction following SCI. A better understanding of this syndrome may provide insights into how the CNS controls the immune system. Furthermore, the identification of patients suffering from spi­nal cord injury as immunocompromised is a clinically relevant, yet widely underappreci­ated finding.
Leapfrog Representation and Extremism: A Study of American Voters and Their Members in Congress
Authors: BAFUMI JOSEPH , HERRON MICHAEL C.
Published: September 2010

We consider the relationship between the preferences of American voters and the preferences of the U.S. legislators who represent them. Using an Internet-based, national opinion survey in conjunction with legislator voting records from the 109th and 110th Congresses, we show that members of Congress are more extreme than their constituents, i.e., that there is a lack of congruence between American voters and members of Congress. We also show that when a congressional legislator is replaced by a new member of the opposite party, one relative extremist is replaced by an opposing extremist. We call this leapfrog representation, a form of representation that leaves moderates with a dearth of representation in Congress. We see evidence of leapfrog representation in states and House districts and in the aggregate as well: the median member of the 109th House was too conservative compared to the median American voter, yet the median of the 110th House was too liberal. Thus, the median American voter was leapfrogged when the 109th House transitioned to the 110th. Although turnover between the 109th and 110th Senates occurred at approximately the same rate as between the 109th and 110th Houses, the Senate appears to be a more moderate institution whose median member does not move as abruptly as that of the House.
LINKING COMMUNITY-BASED SEED PRODUCERS TO MARKETS FOR A SUSTAINABLE SEED SUPPLY SYSTEM
Authors: WITCOMBE J. R. , DEVKOTA K. P. , JOSHI K. D.
Published: September 2010

A review of the outcomes of past attempts at establishing sustainable seed producer groups in Nepal showed that after donor support was withdrawn a lack of marketing skills resulted in the groups no longer producing seed. Learning from this review, when we initiated new attempts at establishing sustainable seed producer groups in Chitwan district, Nepal, we emphasized the strengthening of their marketing and managerial capabilities rather than training in technical issues such as seed quality control. We imparted marketing skills to committee members of farmer groups at an initial training course in Chitwan in 2001. This inspired at least three existing farmer groups in Chitwan, already established for other agricultural activities, to enter into cereal and legume seed production and its marketing. Following their establishment in 2002 we supported them initially by purchasing some of their seed production. This was progressively withdrawn and, after three years, the groups independently marketed all of their substantial seed production. They built up capital reserves mainly from subsidies and by attracting funds from new shareholders with only a small contribution from retained profits that were only about 5% of total turnover. The capital reserves reduced or eliminated the need for loans thus increasing the chances that the enterprises would be sustainable. In contrast, other government-supported groups had practically no cash reserves despite substantial seed sales. By 2010, two of the three groups were still operating and had substantially increased turnover. Shareholders who were also seed producers benefited from being members of the group and from an increased income of 10% by producing seed instead of grain. Our intention in supporting these groups was to promote the scaling out of new rice varieties produced by client-oriented breeding (COB) or identified by participatory varietal selection but most of the seed that was produced was of obsolete varieties. Policies are needed to preferentially promote new varieties by supplying more information about them and increasing the subsidy on their seeds compared with older varieties. Continuing promotion by the organizations that bred them is also desirable but constrained by limited funding for COB.