bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent Melanophore‐Dispersing and Tyrosinase‐Stimulating Activity of Synthetic Leucine9‐α‐melanotropin
Authors: Eberle Alex , Schwyzer Robert
Published: December 2004

Leucine9‐α‐melanotropin ([Leu9]α‐MSH) was synthesized in homogeneous solution by a fragment condensation approach, and it was assayed for its melanophore‐dispersing and its tyrosinase‐stimulating activity with a reflectometricin vitrofrog skin assay and with cultured mouse melanoma cells, respectively. In both assay systems, parallel log dose‐response curves were obtained for ([Leu9)]α‐MSH and α‐MSH; however, in the frog skin assay the activity of the title compound was 1 middot; 1010Units/mmol,i.e.25% of the activity of α‐MSH, whereas its tyrosinasestimulating potency was only 1% compared to α‐MSH (EC50= 2.5 · 10−7M). This indicates a major difference in the recognition/stimulation process of the receptors of the two cell types.
α‐Melanotropin Labelled at its Tyrosine2 Residue: Synthesis and Biological Activities of 3′‐Iodotyrosine2‐,3′‐125Iodotyrosine2‐,3′,5′‐Diiodotyrosine2‐, and (3′,5′‐3H2)tyrosine2‐α‐Melanotropin, and of Related Peptides
Authors: Eberle Alex , Hübscher Willy
Published: December 2004

α‐MSH was labelled at its tyrosine2 residue with tritium and iodine. Several synthetic routes were investigated by preparing 13 precursor or mode compounds and 4 different labelled products (via about 40 intermediates). Their melanotropic activity was determined with an in vitro frog skin assay and, for some of the compounds, with a tyrosinase assay. The tritiation was performed on [Tyr(I2)2]α‐MSH by catalytic halogen/tritium exchange, yielding α‐MSH of high specific radioactivity (34 Ci/mmol) and full biological activity. Iodination was studied in detail using five different techniques. An equimolar chloramine T procedure proved to be the most convenient and reproducible method, resulting in monoiodinated α‐MSH containing 99% of the label in position 2. The biological activity was 50% that of α‐MSH; the specific radioactivity, determined in a competitive binding assay with a highly specific α‐MSH antiserum and [Tyr(I)2]α‐MSH as competitor, was 1530 Ci/mmol. The labelling techniques and the bioligical results are discussed.
The Radical Anion of 1,2‐Diphenylcyclopentene
Authors: Gerson Fabian , Martin William B. , Wydler Christoph
Published: December 2004

ESR. and ENDOR. studies are reported for the radical anions of 1,2‐diphenylcyclopentene (3) and its di(pe+deuteriophenyl)‐derivative (3‐D10). Comparison of the coupling constants of the phenyl protons in 3\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}. with the analogous values for the radical anions of 1,2‐diphenyl substituted cyclopropene (1) and cyclobutene (2) reveals regular changes in the sequence 1\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, 2\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, 3\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}, which are caused by an increasing twist of the phenyl groups about the C(1), C(1′)‐ and C(2), C(1″)‐bonds linking them to the ethylene fragment. Such a twist is shown to be also responsible for the large difference in the coupling constants of the methylene β‐protons in 3\documentclass{article}\pagestyle{empty}\begin{document}$ ^{\ominus \atop \dot{}} $\end{document}. (0.659 and 0.293 mT). It is suggested that ‐ in order to minimize the losses caused by this twist in the π‐delocalization energy ‐ the 2 pz‐axes at the centres 1 and 2 deviate from a perpendicular orientation to the mean plane of the cyclopentene ring. A deviation by 19° from such an orientation is required to account for the observed β‐proton coupling constants in terms of their conventional cos2‐dependence on the dihedral angles θ.
Synthese und Chiralität von (5R, 6R)‐5,6‐Dihydro‐β, ψ‐carotin‐5,6‐diol, (5R, 6R, 6′R)‐5,6‐Dihydro‐β, ε‐carotin‐5,6‐diol, (5S, 6R)‐5,6‐Epoxy‐5,6‐dihydro‐β, ψ‐carotin und (5S, 6R, 6′R)‐5,6‐Epoxy‐5,6‐dihydro‐β,ε‐carotin
Authors: Eschenmoser Walter , Uebelhart Peter , Eugster Conrad Hans
Published: December 2004

Synthesis and Chirality of (5R, 6R)‐5,6‐Dihydro‐β, ψ‐carotene‐5,6‐diol, (5R, 6R, 6′R)‐5,6‐Dihydro‐β, ε‐carotene‐5,6‐diol, (5S, 6R)‐5,6‐Epoxy‐5,6‐dihydro‐β,ψ‐carotene and (5S, 6R, 6′R)‐5,6‐Epoxy‐5,6‐dihydro‐β,ε‐carotene

Wittig‐condensation of optically active azafrinal (1) with the phosphoranes 3 and 6 derived from all‐(E)‐ψ‐ionol (2) and (+)‐(R)‐α‐ionol (5) leads to the crystalline and optically active carotenoid diols 4 and 7, respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9, respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].
Carotenoids of Rhizobia. IV. Isolation and structure elucidation of the carotenoids of a mutant of Rhizobium lupini
Authors: Beyer Peter , Kleinig Hans , Englert Gerhard , Meister Walter , Noack Klaus
Published: December 2004

The structures of the main carotenoid pigments from the mutant 1‐207 of Rhizobium lupini were elucidated by spectroscopic techniques (UV./VIS., CD., 270 MHz 1H‐NMR., and MS.). Ten carotenoids were identified, namely β,β‐carotene (1), β,β‐caroten‐4‐one (echinenone, 2), β,β‐carotene‐4,4′‐dione (canthaxanthin, 3), (3S)‐3‐hydroxy‐β,β‐caroten‐4‐one ((3S)‐3‐hydroxyechinenone, 4), (2R, 3R)‐β,β‐carotene‐2,3‐diol (5), (3S)‐3‐hydroxy‐β,β‐carotene‐4,4′‐dione ((3S)‐adonirubin, 6), (2R, 3S)‐2,3‐dihydroxy‐β,β‐caroten‐4‐one (7), (2R, 3S)‐2,3‐dihydroxy‐β,β‐caroten‐4,4′‐dione (8), (2R, 3S, 2′R, 3′R)‐2,3,2′,3′‐tetrahydroxy‐β,β‐caroten‐4‐one (9) and the corresponding (2R, 3S, 2′R, 3′S)‐4,4′‐dione (10). Structures 5, 7, 8 and 10 have not been reported before. From the observed carotenoid pattern it is concluded that in this mutant the oxidation to 4‐oxo compounds is favoured compared to the hydroxylation at C(3) and C(2).
Über Pterinchemie. 71. Mitteilung. Trennung der Diastereomeren (6R)‐ und (6S)‐5,6,7,8‐Tetrahydro‐L‐neopterin
Authors: Furrer Hans‐Jürg , Bieri Jost H. , Viscontini Max
Published: December 2004

Separation of the Diastereomers (6R) and (6S)‐5,6,7,8‐Tetrahydro‐L‐neopterin

The mixture of the diastereomers of the pentaacetylderivative IV of (6RS)‐5,6,7,8‐tetrahydro‐L‐neopterins could be separated by fractional crystallisation in methanol into the diastereomers IV A and IV B. Hydrolysis with hydrochloric acid gives the pure, diastereomeric, (6R)‐ and (6S)‐5,6,7,8‐tetrahydro‐L‐neopterins.
The Radical Anions of Some Substituted [2.2]Paracyclophanes
Authors: Fürderer Peter , Gerson Fabian , Ohya‐Nishiguchi Hiroaki , Böhm Ingrid , Hopf Henning
Published: December 2004

The radical anions of the following substituted [2.2]paracyclophanes have been characterized by ESR. and ENDOR. spectroscopy: 4, 16‐dicyano‐ (o‐2), 4, 12‐dicyano‐ (p‐2), 4,5,12,13‐tetracyano‐ (3) and 4,5,12,13‐tetrakis (alkoxycarbonyl)‐ [2.2]paracyclophanes (4‐R, where R = Me, Et, iPr or tBu is the ester alkyl group); 4,5‐bis(methoxycarbonyl)[2.2]paracyclophane‐12, 13‐dicarboxylic anhydride (5); [2.2]paracyclophane‐4,5:12, 13‐tetracarboxylic bisanhydride (6) and bisimides (7‐R, where R = H, D, Me or Ph is the substituent at the imide N‐atom). Comparison of the hyperfine data for these radical anions with those for analogously substituted derivatives of benzene indicates that the most prominent coupling constants are approximately halved on passing from the latter to the former. Lowering of the symmetry, as a consequence of ion pairing, has been observed for the radical anions 4‐iPr\documentclass{article}\pagestyle{empty}\begin{document}$^{\ominus \atop \dot{}}$\end{document} and 4‐tBu\documentclass{article}\pagestyle{empty}\begin{document}$^{\ominus \atop \dot{}}$\end{document} associated with the counterion K⊕ in 1,2‐dimethoxyethane at 183 K, but not for 4‐Me\documentclass{article}\pagestyle{empty}\begin{document}$^{\ominus \atop \dot{}}$\end{document} and 4‐Et\documentclass{article}\pagestyle{empty}\begin{document}$^{\ominus \atop \dot{}}$\end{document} under the same conditions. This result suggests that the migration of K⊕ between the preferred sited in two equivalent ion pairs is slowed down by the steric hindrance arising from the bulky iPr and tBu ester groups.
Die Cope‐Umlagerung als Prinzip einer repetierbaren Ringerweiterung
Authors: Bruhn Jens , Heimgartner Heinz , Schmid Hans
Published: December 2004

The Cope Rearrangement, a Reaction for Repeatable Ring Expansions

Starting with the unsaturated β‐ketoesters of type I, a vinyl group is introduced into the β‐position by 1,4‐addition of vinyl magnesium chloride to give II (Scheme 3). Treatment of the β‐ketoester II with phenyl vinyl sulfoxide in the presence of sodium hydride yields the sulfoxides III, which on thermolysis lead to the α, β‐divinyl ketoesters of type IV via elimination of sulfinic acid (Scheme 3). The Cope‐System IV undergoes rearrangement to V, which is again an unsaturated β‐ketoester. The latter is suitable for a further ring expansion sequence. These reaction steps were carried out with the nine‐, twelve‐ and fifteen‐membered ketoesters 32, 33 and 34, as well as with the open‐chain compound 35 (Table 1). With the cyclohexane derivative 31, ring expansion could not be achieved with the described sequence.
Beitrag zur absoluten Konfiguration der Spermin‐Alkaloide O‐Methylorantin und Aphelandrin. 175. Mitteilung über organische Naturstoffe
Authors: Dätwyler Peter , Bosshardt Herbert , Hesse Manfred , Johne Siegfried
Published: December 2004

Contribution to the Absolute Configuration of the Spermine Alkaloids O‐Methylorantine and Aphelandrine

The absolute configuration of the spermine alkaloid O‐methylorantine (1) isolated from Chaenorhinum minus (L.) WILLK. ET LGE. and Ch. villosum (L.) WILLK. ET LGE. was determined. Besides the difference in the substitution at C(31) (OCH3 versus OH) the constitution of 1 and aphelandrine (2) [6] is the same. This was established by spectroscopic evidence, by isomerization reactions of 2, orantine (4) and their derivatives (Scheme 2), and by degradation reactions of 1 and 4, respectively. The methyl ether 1 of orantine (4), the latter prepared by base catalyzed isomerization from aphelandrine (2), is in all respects identical with the natural O‐methylorantine (1). Orantine (4) is identical (UV., CD., 1H‐NMR. and TLC. evidence) with ephedradine A, recently isolated by Hikino et al. [8], who determined the absolute configuration of ephedradine A by X‐ray analysis. The absolute configuration of aphelandrine (2) was related to the one of 4 by chemical degradation.
Anion Coordination Chemistry: Polyguanidinium Salts as Anion Complexones
Authors: Dietrich Bernard , Fyles Deborah L. , Fyles Thomas M. , Lehn Jean‐Marie
Published: December 2004

The synthesis of a series of polyguanidinium salts of potential interest as anion complexones is described. Among the various synthetic methods investigated, the polyguanidinium salts were found to be most conveniently prepared from polyamines via polynitroguanidine intermediates. The complexation of phosphate and carboxylate anions by these complexones and by related polyammonium salts were studied by analysis of pH‐metric titration data. The ligands studied from relatively stable complexes (log Ks = 2.0–4.0 for PO in water) which also present good selectivities in some cases. Both the stability and the selectivity of complexation are primarily governed by electrostatic forces and thus depend on charge accumulation in the interacting species; structural effects are also observed. Since the binding is primarily electrostatic, polyammonium salts from more stable complexes (at a given charge) than do polyguanidinium salts. However, whereas the complexation properties of the latter are independent of pH, the complexes of the former are observed only in the limited ranges of pH where both the protonated polyamine and the anion of interest can coexist. The polycationic ligands may, in principle, form chelate type anion complexes. Comparison with the corresponding single binding sites reveals an increase in complexation constant of about two or three orders of magnitude; this may be considered as a thermodynamic indication of a chelate effect for the polydentate ligands (by analogy with the well known effects displayed by cation complexones); however, structural data on the formation of chelate ‘rings’ are not yet available. The nature of the complexes and the prospects of anion complexones in various fields are discussed.
Die Synthese von 4‐substituierten Bicyclo[2.2.2]oct‐1‐yl‐p‐nitrobenzolsulfonaten
Authors: Grob Cyril A. , Rich Roland
Published: December 2004

Synthesis of 4‐Substituted Bicyclo[2.2.2]oct‐1‐yl‐p‐Nitrobenzenesulfonates

The syntheses of the 4‐substituted bicyclo[2.2.2]oct‐1‐yl‐p‐nitrobenzenesulfonates 1a–2s are described.
Mehrkernige Kobaltkomplexe. V. Präparative Herstellung von Tetrakis (äthylendiamin)‐μ‐peroxo‐μ‐amido‐ und μ‐peroxo‐μ‐thiocyanatodikobalt (III)‐Komplexen ausgehend von Tetrakis (äthylendiamin)bis‐(ammin)‐μ‐peroxo‐dikobalt (III)‐tetraperchlorat
Authors: Zehnder Margareta
Published: December 2004

Polynuclear Cobalt Complexes. V. Preparation of tetrakis (ethylenediamine)‐μ‐peroxo‐μ‐amido and μ‐peroxo‐μ‐thiocyanato‐dicobalt (III) complexes starting from tetrakis (ethylenediamine)bis‐(ammine)‐μ‐peroxo‐dicobalt (III)‐tetraperchlorate

Racemic tetrakis (ethylenediamine)‐μ‐peroxo‐μ‐amido‐dicobalt (III) thiocyanate and its corresponding hydroperoxo‐ and superoxo‐complexes have been isolated from [(en)2(NH3)Co(O2)(NH3)(en)2](ClO4)4. A new binuclear peroxo complex containing thiocyanate as bridging ligand was prepared by the same method. The stretching frequencies of the CN‐ and CS‐group as well as the NCS‐bending frequence in the IR. spectrum of [(en)2Co(O2, SCN)Co(en)2](NO3)3 suggest that the μ‐thiocyanato group is N‐bonded (2050, 750, 475 cm−1). A comparison of IR. spectra of known singly and doubly bridged μ‐peroxo complexes is made. Characteristic absorption bands, assignable to ν(OO) and ν(CoO) are given.
Chemie des 2‐Aminospiro[indan‐1,3′‐pyrrolidin]‐Systems
Authors: Strasser Michael , Loosli Hans‐Rudolf , Zardin‐Tartaglia Therese
Published: December 2004

The chemistry of the 2‐aminospiro[indan‐1,3′‐pyrrolidine]system

2‐Aminospir[indan‐1,3′‐pyrrolidines] 1 are easily synthesized from the α‐hydroxyiminoketones 6 and 19 (Schemes 2 and 3, and 6 respectively). Removal of the N‐acetyl group in the intermediate 8 of the trans series induces transposition to the 3a‐aminomethyl‐indano[2,1‐b]pyrrolidine system. The configurations of all compounds have been determined by 1H‐NMR. spectroscopy.
Synthese von [1,2,4]Triazolo [1,5‐a]chinazolinen. Ableitung der Konformation von Substituenten mit Hilfe der 13C‐NMR.‐Spektroskopie
Authors: Heckendorn Roland , Winkler Tammo
Published: December 2004

Synthesis of [1,2,4]Triazolo[1,5‐a]quinazolines. Assignment of the Conformation of Substituents with the Aid of 13C‐NMR. Spectroscopy

The synthesis of [1,2,4]triazolo[1,5‐a]quinazolines by condensation of 2‐hydrazinobenzoic acid with N‐cyano‐imidates is reported. The preferred conformation of substituents at C (5), e.g. N (CH3)2, N (CH3)NH2, N (CH3)OH, relative to the aromatic system is deduced with the aid of 13C‐NMR. chemical shifts and proton nuclear Overhauser effect experiments.
13C‐ and 1H‐NMR. Assignments for colchicine derivatives
Authors: Hufford Charles D. , Capraro Hans‐Georg , Brossi Arnold
Published: December 2004

The 13C‐NMR. spectra of a number of colchicine derivatives are given comprising examples of the normal series (4→10), iso series (11→16) and colchicine series (17), which were either reported in the literature or obtained by partial synthesis or degradation reactions. The 13C‐NMR. assignments were made by comparisons with known compounds and selective single‐frequency offresonance decoupling experiments. Selective proton decoupling experiments have also allowed assignments of the H—C(11) and H—C(12) protons of the iso and colchicine series.
Struktur von sechs Coleonen (Diterpenen) aus Solenostemon monostachys (P. BEAUV.) BRIQ. (Labiatae)
Authors: Miyase Toshio , Rüedi Peter , Eugster Conrad Hans
Published: December 2004

Structures of Six Coleons (Diterpenoids) from Solenostemon monostachys (P. BEAUV.) BRIQ. (Labiatae)

The above mentioned African labiate has been investigated for its leaf‐gland pigments. Besides the already known coleons C (1) and H (2), 2a‐formoxy‐coleon C (3), 12β‐O‐acetyl‐coleon Z (7), 12β‐O‐acetyl‐7‐O‐formyl‐7‐O‐desacetyl‐coleon Z (8) and a not separated mixture of 17‐acetoxy‐12β‐O‐acetyl‐coleon Z (9a) and 12β‐O‐acetyl‐17‐formoxy‐coleon Z (9b) have been isolated.
Nucleophile Aminoalkylierung mit Thiopivalamiden
Authors: Lubosch Winfried , Seebach Dieter
Published: December 2004

Nucleophilic Aminoalkylation with Thiopivalamides

Vorläufige Mitt. [1].

Of the twelve thioamides 7a‐e and 8a‐g, only N,N‐dimethylthiopivalamide (7a) could be metallated at the CH‐group in a‐position to the N‐Atom. The reagent 9 thus obtained (Table 1) reacts in high yields with primary haloalkanes, with aldehydes, and with non‐enolizable ketones (Table 2). As shown in Scheme 1, the products can be hydrolyzed to pivalamides, cleaved to secondary amines, or reduced to neopentylamines (see 18/19, 15/equation (4) and (5), and 16/20, respectively).
Globularifolin, A New Acyl Iridoid Glucoside from Globularia cordifolia
Authors: Chaudhuri Ratan K. , Sticher Otto
Published: December 2004

Six iridoid glucosides have been isolated from Globularia cordifolia by the combination of open column ‐ and high performance liquid chromatography. The structure of the new compound, named globularifolin, and the identity of the others have been established by chemical transformations and spectral evidence of the compounds and their derivatives.
2‐Oxocephems. II. ‐ synthesis of 2‐oxocephalexin from hetacillin
Authors: Ernest Ivan
Published: December 2004

2‐Oxocephalexin 4, a very labile representative of the novel group of 2‐oxocephem‐4‐carboxylic acids, has been synthesized from hetacillin.
N,N,N′,N′‐Tetrabutyl‐3,6‐dioxaoctan‐dithioamid, Ionophor mit Selektivität für Cd2+
Authors: Schneider Jürg K. , Hofstetter Peter , Pretsch Ernö , Ammann Daniel , Simon Wilhelm
Published: December 2004

N,N,N′,N′‐Tetrabutyl‐3,6‐dioxaoctane‐dithioamide, an Ionophore with Selectivity for Cd2+

The dioxa‐dithioamide 3 behaves as a highly selective ionophore for Cd2+ in solvent polymeric membranes. It induces cation‐permselectivity in these membranes with a transference number of 1 for Cd(NO3)2‐ and of 2 for CdCl2‐solutions. In the presence of a proton carrier, 3 may be used to selectively pump Cd2+ through membranes by coupling with a pH gradient.
Synthesis of (±)‐4‐Demethoxydaunomycinone by Double Diels‐Alder Additions to 2, 3, 5, 6‐Tetramethylidene‐7‐oxanorbornane
Authors: Bessière Yvonne , Vogel Pierre
Published: December 2004

Sequential Diels‐Alder additions of methylvinyl ketone and dehydrobenzene to 2, 3, 5, 6‐tetramethylidene‐7‐oxanorbornane (4) yielded the (5, 12‐epoxy‐1, 2, 3, 4, 5, 6, 11, 12‐octahydro‐2‐naphtacenyl) methyl ketone (10) which, in few steps was oxidized to a precursos of (±)‐4‐demethoxydaunomycinone. The preparations of two precursors of anthracyclinones, the (5‐acetoxy‐) and (12‐acetoxy‐1, 2, 3, 4‐tetrahydro‐2‐naphtacenyl) methyl ketones (14, 15) are presented. The synthesis of 6, 13‐epoxy‐6, 13‐dihydropentacene (8) is also reported.
Volumes of Activation for Dimethylsulfoxide and N,N‐Dimethylformamide Exchange with Hexasolvates of Aluminium (III) and Gallium (III) Ions in Deuterionitromethane Solution
Authors: Ammann Claude , Moore Peter , Merbach André E. , McAteer Colin H.
Published: December 2004

High‐pressure 1H‐NMR. has been used to determine volumes of activation (ΔV#) for solvent exchange with [M(S)6]3+ ion (M = Al(III), Ga(III); S = dimethylsulfoxide (DMSO) and N,N‐dimethylformamide (DMF)) in [2H]3‐nitromethane solution. For Al(III),Δ V# = + 15.6 ± 1.4 (S = DMSO, 358.5 K) and ΔV# = + 13.7 ± 1.2 cm3mol−1 (S = DMF, 354.5 K), whilst for Ga(III), ΔV# = + 13.1 ± 1.0 (S = DMSO, 334.6 K) and ΔV# = +7.9 ± 1.6 cm3mol−1 (S= DMF, 313.8 K). Variable temperature studies over a temperature range of 107.2 K (Al(III)) and 101.1 K (Ga(III)) were carried out for solvent exchange with [M(DMF)6]3+ ions in [2H]3‐nitromethane solution, using stopped‐flow NMR, and conventional linebroadening, and gave ΔH# = 88.3 ± 0.9 and 85.1 ± 0.6 kJ+ mol−1, and ΔS# = 28.4 ± 2.7 and 45.1 ± 1.9 JK−1 mol−1 for Al(III) and Ga(III) ions respectively. All of these results are consistent with dissociative modes of activation.
Carotinoid‐Glycosylester 4. Mitteilung. Synthese von 8′‐Apo‐β‐carotin‐8′‐säure‐(β‐D‐glucosyl)ester und Vitamin‐A‐säure‐(β‐D‐glucosyl)ester
Authors: Pfander Hanspeter , Läderach Manfred , Wittwer Fritz
Published: December 2004

Carotenoid Glycosyl Esters Synthesis of β‐D‐Glucosyl 8′‐Apo‐β‐carotene‐8′‐oate and β‐D‐Glucosyl Vitamin‐A‐oate (β‐D‐Glucosyl Retionate)

β‐D‐glucosyl 8′‐apo‐β‐carotene‐8′‐oate (III) and β‐D‐glucosyl vitamin‐A‐oate (VI) were regio‐ and stereoselectively synthesized in high yields from the N‐acylimidazoles I and IV, respectively, or from the N‐acyltriazoles II and V, respectively, and unprotected β‐D‐glucose, according to the method described for the synthesis of di(β‐D‐glucosyl) 8,8′‐diapo‐carotene‐8,8′‐dioate [1]. It seems that this method can generally be applied for the synthesis of β‐D‐glucosyl esters of polyene carboxylic acids.
Eine einfache Methode zur Herstellung von Benzoxazolen
Authors: Seha Zdenek , Weis Claus D.
Published: December 2004

A Facile Method for the Synthesis of Benzoxazoles

The preparation of benzoxazoles by a facile one‐pot reaction is reported. The reaction of carboxylic acids with 2‐chloro‐N‐methyl‐Δ1‐pyrrolinium chloride in an excess of N‐methyl‐2‐pyrrolidone afforded carboxylic acid chlorides which were converted subsequently to their 2‐hydroxyanilides by addition of 2‐aminophenols. Cyclization of the 2‐hydroxy‐anilides at elevated temperatures furnished the benzoxazoles in high yield and purity.
Réactions chimiques oscillantes III. Effets de la température et de la composition chimique sur la «période d'induction» des systèmes BrO/Ce4+/Cyclohexanone et BrO/Ce4+/Cyclopentanone
Authors: Farage par Vincent J. , Janjic Désimir
Published: December 2004

Oscillating Chemical Reactions. III. Effects of the Temperature and Chemical Composition on the ‘Induction Period’ of the BrO/Ce4+/Cyclohexanon and BrO/Ce4+/Cyclopentanon Systems

A study of the influence of the temperature and composition of the BrO/Ce4+/cyclohexanon (S1) and BrO/Ce4+/cyclopentanon (S2) systems has shown a very particular behaviour for τind. for a given ratio α of concentrations:

Moreover, for 0.27 ⩽ α ⩽ 0.32, log1/τind. is no longer a linear function of the inverse of the temperature: a break in the line log1/τind. = f(1/T) occurs.
Eine einfache Allencarbonsäureester‐Synthese mittels der Wittig‐Reaktion
Authors: Lang Robert W. , Hansen Hans‐Jürgen
Published: December 2004

A Simple Synthesis of Alkyl Allenecarboxylates (Allenic Esters) by the Wittig‐Reaction

A simple one‐pot synthesis of variously substituted α‐allenic esters (7–23, cf. Scheme 4) is described. Either of the phosphonium salts 1 and 2 or the phosphoranes 3–6 in methylene chloride (or acetonitrile) when treated with acid chlorides at room temperature in the presence of triethylamine give the corresponding allenic compounds in fairly good yields (cf. Tables 3a and 3b). This procedure shows for the first time, that the Wittig‐reaction with acid chlorides as starting material can also be used for the synthesis of 2‐H‐substituted allenic esters (7–13; for numbering see Scheme 7). The deuterium labeled compounds 26–31 (cf. Scheme 7) are prepared in the same manner. The course of the reaction involves an in situ generation of ketenes which are trapped by the resonance stabilized phosphonium ylides. The thus formed betains readily decompose, already at room temperature, to the anticipated allenes by the well known Wittig‐reaction.
Etude du Comportement Photochimique de quelques Diaryl‐1,3‐triazènes
Authors: Julliard Par Michel , Vernin Gaston , Metzger Jacques
Published: December 2004

Study of the Photochemical Behaviour of Some Diaryl‐1,3‐triazenes

The photolysis of Diaryl‐1,3‐triazenes gives products whose structures are consistent with a cage recombination process of homolytically formed radicals and subsequent abstraction of hydrogen from the solvent molecules by arylamino radicals. In aromatic solvents, a free‐radical chain process leads to the formation of products resulting from the homolytic substitution on the solvent. Quenching experiments show that singlet and triplet excited states are reactive but that intersystem crossing efficiency is low.
Photochemical Rearrangement of a Steroidal α, β‐Epoxylactam. Photochemical reactions, XII [1]
Authors: Cánovas Antonio , Bonet Juan‐Julio
Published: December 2004

The UV. irradiation of 17β‐hydroxy‐4α, 5α‐epoxy‐2‐azaandrostan‐3‐one (1) yields 17β‐hydroxy‐2‐aza‐10 (5 → 4‐abeo)‐4ζ (H)‐androsta‐3,5‐dione (3).
15N‐NMR. Studies of Aminopyridines, Aminopyrimidines and of Some Diazine N‐Oxides
Authors: Städeli Werner , Philipsborn Wolfgang Von , Wick Alexander , Kompiš Ivan
Published: December 2004

15N‐NMR. spectra of mono‐ and diaminopyridines, and mono‐, di‐ and triaminopyrimidines including trimethoprim and other dihydrofolate reductase inhibitors have been studied in neutral and acidic media. Complete chemical shift assignments are given. Ring‐nitrogen shifts are discussed in terms of β‐, χ‐ and δ‐substituent effects of amino and alkyl groups. Protonation states in TFA‐ and FSO3H‐solution and protonation increments for the 15N‐shifts of ring and amino N‐atoms are determined. A linear correlation is observed between amino substituent effects (Δδ(15N)) on the ring N‐atom in aminopyridines and corresponding Δδ (13C) values in aminobenzenes and, similarly, between Δδ(15N) values in aminopyrimidines and Δδ(13C) values in aminopyridines. Assignment of the 15N‐NMR. spectra of pyrimidine N‐oxides, pyrazine N‐oxides and pyridazine N‐oxides is achieved by comparison with 14N‐NMR. data and with the aid of Yb(fod)3‐induced shifts. One‐bond 15N, 1H‐coupling constants are reported for aminopyridines and aminopyrimidines and discussed in terms of conjugative interaction between NH2‐group and ring system.
Photoreaktionen des 3‐Methyl‐4‐phenylsydnons
Authors: Pfoertner Karl‐Heinz , Foricher Joseph
Published: December 2004

Photoreactions of 3‐Methyl‐4‐phenylsydnone

A procedure for the synthesis of 3‐methyl‐4‐phenylsydnone (1) is given. UV. irradiation of 1 in solution generates the nitrile‐imine 4 which reacts with activated C, C double bonds and with heterocumulenes to give five‐membered heterocycles. In contrast to the 2H‐azirines which photochemically react with the C, O double bond of phenylisocyanate, 4 adds to the C, N double bond of the latter.
Nucleophilic addition to C,C double bonds. III. Chemical reactivity of 1endo, 4endo: 5exo, 8exo‐dimethano‐1,2,3,4,4a,5,8,8a‐octahydronaphthalen‐10syn‐ol and X‐ray structure analysis of its p‐nitrobenzoate
Authors: Pfund Rolland A. , Bernd Schweizer W. , Ganter Camille
Published: December 2004

The title compound 1 is a further example of an olefinic alcohol that undergoes ether formation under basic conditions (→ 3) although the double bond is not activated by an electron‐attracting group. This unusual reactivity is due to steric compression, which is increased in the 10‐methyl analogue 2. This forms the corresponding ether 7 at a much higher rate. ‐ In a deuteriated medium, base‐catalysed cyclization of 1 gives the exo‐deuteriated ether 6, corresponding to trans‐addition. ‐ An X‐ray structure analysis of 4, the p‐nitrobenzoate of 1, is presented.
Citrus‐Carotinoide. 1. Mitteilung. Synthese von Apocarotinoiden mit einer anders gelagerten Methylgruppe; Strukturaufklärung von Citrus‐Carotinoiden
Authors: Pfander Hanspeter , Hadorn Martin , Lachenmeier Andreas , Englert Gerhard
Published: December 2004

Synthesis of Apocarotenoides with a Shifted Methyl Group; Structure Elucidation of Citrus‐Carotenoides

With regard to the investigation of the biosynthesis of the C30‐carotenoids in citrus fruits apocarotenoids with a methyl group shifted by one position (diapocarotenoids) were synthesized. Characteristical differences, especially in the 270‐MHz‐1H‐NMR. spectra between the apo‐ and the diapocarotenoids are reported. The comparison of the natural pigments with the synthetic compounds proves that the natural products belong to the apocarotenoids as has been postulated earlier.
Synthesis, Enzymic Degradation, Lipophilic Properties, and Biological Activity of [D‐Alanine2, t‐butylglycine5]enkephalin Amide
Authors: Fauchère Jean‐Lue , Petermann Claudia
Published: December 2004

L‐Cα‐t‐Butylglycine (Bug), its amide, methyl ester, and Nα‐t‐butoxycarbonyl derivative were prepared by an asymmetric synthesis, and the Hansch side‐chain hydrophobic (lipophilicity) parameter determined. A new enkephalin analogue, H · Tyr‐D‐Ala‐Gly‐Phe‐Bug · NH2 was synthesized which is pharmacologically active in two in vitro assays and strongly resistant against a number of enzymes in vitro.
Heterocyclic spiro‐naphthalenones. Part IV. Synthesis of some 3,4‐dihydrospiro [naphthalene‐2(1H),2′‐pyrrolidine]‐1‐ols from 3,4‐dihydrospiro [furan‐2(5H),1′(2′H)‐naphthalene]‐2′,5‐dione
Authors: Berney Daniel , Schuh Karlheinz
Published: December 2004

Depending on the experimental conditions the spirolactone 3 on treatment with methylamine gave compounds 6, 7 or the rearranged product 4. Compound 4 was used to prepare the title compounds 11–13, 15, 18–20 and other derivatives.
Heterocyclic Spiro‐naphthalenones. Part V. Synthesis of Some 2‐Benzazepines from 3,4‐Dihydrospiro [furan‐2‐(5H), 1′(2′H)‐naphthalene]‐2,5‐dione
Authors: Berney Daniel , Schuh Karlheinz
Published: December 2004

Compound 2 was rearranged on treatment with 2N NaOH to the 2‐benzazepine‐3‐propanoic

See footnote (5) of the preceding paper.

acid 3. Some aspects of the chemistry of this acid were studied.
Nickel‐catalyzed Asymmetric Alkylation of Some Chiral and Achiral Allylic Alcohols. Preliminary communication
Authors: Consiglio Giambattista , Morandini Franco , Piccolo Oreste
Published: December 2004

[(−) (R)‐1,2‐bis (Diphenylphosphino)‐1‐phenylethane]nickel (II) chloride was found to catalyze the asymmetric alkylation of some chiral and achiral allylic alcohols with Grignard reagents, leading to the formation of optically active olefins. Enantiomer discrimination of the substrate takes place in the alkylation of chiral allylic alcohols.
The Acetolysis of exo‐ and endo‐5,6‐Dimethylidene‐2‐Norbornyl p‐Bromobenzenesulfonates and of their Optically Active and Deuterium‐Labelled Derivatives
Authors: Sonney Jean‐Marie , Vogel Pierre , Burger Ulrich
Published: December 2004

The buffered (AcOK) acetolyses of exo, (11) and endo‐5, 6‐dimethylidene‐2‐norbornyl brosylate (12) yielded exo5, 6‐dimethylidene‐2‐norbornyl (16) and (3‐methylidene‐2‐nortricyclyl)methyl acetates (18). Endo‐5, 6‐dimethylidene‐2‐norbornyl (17) and 2‐methylidene‐3‐tricyclo [3.2.1.03,6]octyl acetates (20) could not be detected. The titrimetric rate constants of the acetolysis of 11 (kt(exo)=4.49 ± 0.02) · 10−5 s−1 at 25°, ΔH≠=23.6 ±0.7 kcal mol−1, ΔS≠=0.7 ±2 calmol−1 K−1 and 12 (kt(endo)=1.9 ±0.08) · 10−9 s−1 at 25°, ΔH≠=27 ±1 kcal mol−1, ΔS≠=‐8 ±2.5 calmol−1 K−1) were measured and compared with the polarimetric rate constants (kα/k(exo)=6.8 at 25°,(kα/k(exo)=1.0 at 121°) of the buffered acetolyses of the optically active brosylates (+)‐11 and (+)‐12 . Neither a common‐ion (KOBs) nor a special ion effect (LiClO4) on kt(endo) could be detected, although external return might well intervene as some exo‐5,6‐dimethylidene‐2‐norbornyl tosylate (21) was formed upon solvolysis in the presence of KOTs. Acetolysis of (+)‐11 yielded completely racemized products, whereas (+)‐12 led to incomplete racemization. The buffered acetolysis of exo‐(3exo‐D)‐5,6‐dimethylidene‐2‐norbornyl brosylate (24) furnished (3exo‐D)‐(26:37.5%), exo‐(7syn‐D)‐5,6‐dimethylidene‐2‐norbornyl brosylate (27: 37.5%) and [(5anti‐D)‐3‐methylidene‐2‐nortricyclyl]methyl acetates (28:25%). The acetolysis of endo‐(2exo‐D)‐5,6‐dimethylidene‐2‐norbornyl brosylate (25) yielded (2endo‐D)‐(29: 54%), exo‐(1‐D)‐5,6‐dimethylidene‐2‐norbornyl (30: 36%) and [(6‐D)‐3‐methylidene‐2‐nortricyclyl]methyl acetates (31: 10%). Product analysis and deuterium label distribution was established by a combination of GC., 1H‐NMR., 2H‐{1H}‐NMR. and MS. techniques. The results are rationalized by invoking anchimerically assisted ionization of the exo‐brosylate 11 to symmetrical ion‐pairs (cyclopropylcarbinyl cation intermediates) which undergo internal (and probably also external) return. Acetolysis of the endo‐brosylate 12 is not anchimerically assisted and leads initially to non‐symmetrical ion pairs. These evolve to symmetrical ion pair intermediates or, to a minor extent, are intercepted by solvent.
The Penems, a New Class of β‐Lactam Antibiotics. 6. Synthesis of 2‐alkylthiopenem carboxylic acids
Authors: Lang Marc , Prasad Kapa , Gosteli Jaques , Woodward Robert B.
Published: December 2004

A synthesis of 2‐alkylthiopenems by an intramolecular Wittig‐type reaction between a phosphorane and a trithiocarbonate ester is described.
Ruthenium Dioxide Electrodes as Suitable Anodes for Water Photolysis
Authors: Neumann‐Spallart Michael , Kalyanasundaram Kuppuswamy , Grätzel Carole , Grätzel Michael
Published: December 2004

This paper presents a cell system in which a photoinduced redox reaction occurs in the cathodic compartment which is coupled to a RuO2‐anode. The light induced oxidation of the ruthenium complex Ru (bipy) by peroxodisulfate is used to illustrate that even under diffuse room light irradiation the photopotentials developed at the Pt‐cathode are sufficient to afford water oxidation in the anode compartment. The oxygen produced at the RuO2‐electrode stands in a stochiometric relation to the current passed through the circuit. Implications for a cell system in which H2 and O2 are produced in separate compartments under illumination are discussed.
Das s‐cis‐/s‐trans‐Konformerengleichgewicht bei Allencarbonsäureestern
Authors: Lang Robert W. , Hansen Hans‐Jürgen
Published: December 2004

The s‐cis/s‐trans Conformational Equilibrium of Allenic Esters

The following UV. and 1H‐NMR. spectroscopic investigations of the allenic compounds 1–9 (cf. Scheme 2) refer for the first time on a concrete experimental base to the preferred s‐trans conformation of the allenic esters 1–6. With an additional allenic increment of 12 nm, the well established Woodward‐Fieser rules in UV. spectroscopy could be extended on conjugated allenic compounds for the calculation of the (π→π*)‐type band position as well as for the prediction of the s‐cis/s‐trans conformational fraction (cf. Scheme 1). From 1H‐NMR. shift experiments we conclude, that even small structural changes at the molecular framework have a measurable influence on the conformational equilibrium. In contrast to the situation in similarly substituted α, β‐unsaturated compounds (14 und 15), the allenic esters (1 and 4) exhibit preferentially s‐trans conformations (cf. Scheme 3), but in both cases, the equilibrium is displaced toward s‐cis conformation, when the α‐position is methyl substituted (e.g. 14 → 15 and 1 → 4).
Ein einfacher und allgemeiner Zugang zu 2‐Fluor‐1,3‐dienen
Authors: Spahić Bojana , Thu Truong Thi My , Schlosser Manfred
Published: December 2004

A Ready and General Access to 2‐Fluoro‐1,3‐dienes

Upon treatment of 1‐chloro‐1‐fluoro‐2‐halomethylcyclopropanes with zinc, fluorodienes are formed in high yield. The general applicability of this method is illustrated by examples using model compounds of the acyclic and cyclic type.
Linking integrin to IP3 signaling is important for ovulation in Caenorhabditis elegans
Authors: Xu Xiaojian , Lee Diana , Shih Hung-Ying , Seo Sehee , Ahn Jeong , Lee Myeongwoo
Published: December 2004

Signals from germ and myoepithelial sheath cells initiate ovulation in Caenorhabditis elegans. The coordinated dilation and contraction of spermatheca lead to subsequent fertilization of oocyte. Either the dominant negative mutant pat‐3 β integrin or disruption of talin expression block ovulation [Cram, E.J., Clark, S.G. and Schwarzbauer, J.E. (2003) Talin loss‐of‐function uncovers roles in cell contractility and migration in C. elegans. J. Cell. Sci. 116, 3871–3878; Lee, M., Cram, E.J., Shen, B. and Schwarzbauer, J.E. (2001) Role of β pat‐3 integrins in development and function of Caenorhabditis elegans muscles and gonads. J. Biol. Chem. 276, 36404–36410], suggesting that the interaction between the cell and the extracellular matrix (ECM) is also important for ovulation. Here, we report that integrin plays an essential role in fertility via IP3 signaling. Sterility caused by RNAi of pat‐3 and ECM molecules was suppressed by increased IP3 signaling. Our data suggest that the cell–ECM interaction controls ovulation via IP3 signaling.
Congenic C57BL/6 µ opiate receptor (MOR) knockout mice: baseline and opiate effects
Authors: Hall F. S. , Li X.‐F. , Goeb M. , Roff S. , Hoggatt H. , Sora I. , Uhl G. R.
Published: December 2004

Homozygous µ‐opioid receptor (MOR) knockout (KO) mice developed on a chimeric C57B6/129SV background lack morphine‐induced antinociception, locomotion and reward. Therefore it appears that MOR largely mediates these morphine actions. However, one factor that could affect the extent of knockout deficits in morphine‐induced behavior is the genetic background against which the gene deletion is expressed. To examine the effect of genetic background chimeric C57B6/129SV MOR knockout mice from the 15th generation of those developed in our laboratory were backcrossed for 10 successive generations with C57BL/6 mice, a strain which is more sensitive to many of the properties of morphine, to produce congenic MOR (conMOR) KO mice. Heterozygote conMOR KO mice display attenuated morphine locomotion and reduced morphine analgesia compared to wild‐type mice. Homozygote conMOR KO mice display baseline hyperalgesia, no morphine place preference, no morphine analgesia and no morphine locomotion. These results are not qualitatively different from those observed in the MOR KO strain with a chimeric C57B6/129SV background, and suggest that although the strain has separate influences on these functions, it does not substantially interact with deletion of the µ opiate receptor gene.
A small‐sample overlapping variance‐ratio test
Authors: Tse Y. K. , Ng K. W. , Zhang Xibin
Published: December 2004

Abstract.  The null distribution of the overlapping variance‐ratio (OVR) test of the random‐walk hypothesis is known to be downward biased and skewed to the right in small samples. As shown by Lo and MacKinlay (1989), the test under‐rejects the null on the left tail seriously when the sample size is small. This property adversely affects the applicability of the OVR test to macroeconomic time series, which usually have rather small samples. In this paper, we propose a modified overlapping variance‐ratio statistic and derive its exact mean under the normality assumption. We propose to approximate the small‐sample distribution of the modified statistic using a beta distribution that matches the (exact) mean and the (asymptotic) variance. A Monte Carlo experiment shows that the beta approximation performs well in small samples.
Single and mixed diets in Collembola: effects on reproduction and stable isotope fractionation
Authors: Scheu S. , Folger M.
Published: December 2004

Reproduction ofHeteromurus nitidus(Collembola) feeding on conidial fungi, ectomycorrhizal fungi and soil algae in single and mixed diets was investigated. Feeding on mixed diets generally increased Collembola reproduction even in combinations of fungi/algae of high food quality with those of low food quality, indicating that Collembola generally benefit from feeding on mixed diets.

The contribution of dietary species in mixed diets to Collembola nutrition was quantified using stable isotope methods. Incorporation of carbon from fungal/algal species intoH. nitidusin mixed diets varied with food quality indicating that Collembola are able to adjust the proportion of food materials ingested to maximize fitness.

Fractionation of13C and15N inH. nitidusfeeding on single and mixed diets varied between diets and differed between juveniles and adults. The trophic structure of fungal feeding soil invertebrates cannot be inferred in a straightforward way from variations in natural abundances of stable isotopes, rather, stable isotope signatures reflect feeding guilds.
Gemcitabine‐induced severe pulmonary toxicity
Authors: Barlési Fabrice , Villani Patrick , Doddoli Christophe , Gimenez Céline , Kleisbauer Jean‐Pierre
Published: December 2004

Gemcitabine is a relatively new deoxycytidine analog (2′,2′‐difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara‐C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine‐induced severe pulmonary toxicity (GISPT) were reported as for Ara‐C. We performed a systematic review of reported cases on the GISPT. Twenty‐nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X‐ray are reticulo‐nodular interstitial infiltrates. It was postulated that the physio‐pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine‐mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.
Myocardial hypertrophy is not a prerequisite for changes in early gene expression in left ventricular volume overload
Authors: Dzimiri Nduna , Al‐Bahnasi Kholod , Al‐Halees Zohair
Published: December 2004

Currently it is not certain whether hypertrophy or the underlying disease is the primary trigger of the alterations in early gene expression in the progression of cardiac disease to end‐stage heart failure. In this study, we tested the notion that in left ventricular overload disorders, the changes in early gene expression in the progression to heart failure is independent of the manifestation of cardiac hypertrophy. We compared the expression of the early genes c‐fos, c‐myc, and c‐jun in six dilated cardiomyopathic hearts (DCM) and 15 patients with left ventricular volume overload (VOL) resulting from mitral/aortic regurgitation and no significant stenosis or hypertrophic manifestations, using eight healthy donor hearts as controls. In VOL, c‐myc was elevated by 88% (P < 0.01) in the left ventricle, 46% in the right ventricle, onefold (P < 0.01) in the left atrium, and 54% (P < 0.05) in the right atrium, while in DCM, it was increased by 71% (P < 0.02), 55%, 48% (P < 0.05) and 91% (P < 0.05), respectively. Similarly, c‐jun was elevated by 41% (P < 0.01) in the left ventricle, 39% (P < 0.05) in the right ventricle, 83% (P < 0.02) in the left atrium and 21% in the right atrium in VOL, while in DCM it was elevated by 13% in the left ventricle, 29% in the left atrium, and 41% in the right atrium, but decreased by 13% in the right ventricle. In contrast, c‐fos was slightly decreased in the left ventricle and atrium of both DCM and VOL, and in left atrium of the VOL group, but remained unchanged in the other myocardial chambers. These results show that, in the human myocardium, the three early genes are regulated differently, possibly in disease‐ and chamber‐specific fashions, and manifestation of left ventricular hypertrophy is not a prerequisite for the elevation in their expression in left ventricular overload disorders.
Centrally injected CDP‐choline increases plasma vasopressin levels by central cholinergic activation
Authors: Cavun Sinan , Savci Vahide , Ulus Ismail H.
Published: December 2004

In the present study, both the effects of intracerebroventricular (i.c.v.) injection of cytidine‐5′‐diphosphate choline (CDP‐choline) on plasma vasopressin levels and the choline involvement of these effects were investigated. I.c.v. administration of CDP‐choline (0.5, 1.0 and 2.0 μmol) increased plasma vasopressin levels dose‐ and time‐dependently. I.c.v. injection of equimolar dose of choline (1 μmol) produced similar vasopressin response. However equimolar dose of cytidine (1 μmol; i.c.v.), the other hydrolysis product of CDP‐choline, did not affect plasma vasopressin levels. Pretreatment of rats with hemicholinium‐3, neuronal high affinity choline uptake inhibitor (20 μg; i.c.v.) blocked the vasopressin response to i.c.v. CDP‐choline (1 μmol). Pretreatment of rats with mecamylamine (50 μg; i.c.v.), a nonselective nicotinic receptor antagonist, abolished the increase in plasma vasopressin induced by CDP‐choline while atropine (10 μg; i.c.v.), nonselective muscarinic receptor antagonist, failed to change the response. In conclusion, intracerebroventricularly injected CDP‐choline can increase plasma vasopressin levels by activating central nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms.
Vinorelbine‐related cardiac events: a meta‐analysis of randomized clinical trials
Authors: Lapeyre‐Mestre Maryse , Gregoire Nicolas , Bugat Roland , Montastruc Jean‐Louis
Published: December 2004

Several cases of cardiac adverse reactions related to vinorelbine (VNR) have been reported in the literature. In order to quantify the incidence of these cardiac events, we performed a meta‐analysis of clinical trials comparing VNR with other chemotherapeutic agents in the treatment of various malignancies. Randomized clinical trials comparing VNR with other drugs in the treatment of cancer were searched in Medline®, Embase®, Evidence‐based Medicine Reviews® databases and the Cochrane library® from 1987 to 2002. Outcomes of interest were severe cardiac events, toxic deaths and cardiac event‐related deaths reported in each publication. We found 19 trials, involving 2441 patients treated by VNR and 2050 control patients. The incidence of cardiac events with VNR was 1.19% [95% confidence interval (CI) (0.75; 1.67)]. There was no difference in the risk of cardiac events between VNR and other drugs [odds ratio: 0.92, 95% CI (0.54; 1.55)]. The risk of VNR cardiac events was similar to vindesine (VDS) and other cardiotoxic drugs [fluorouracil, anthracyclines, gemcitabine (GEM)…]. Even if it did not reach statistical significance because of a few number of cases, the risk was lower in trials excluding patients with cardiac history, and seemed to be higher in trials including patients with pre‐existing cardiac diseases. Vinorelbine‐related cardiac events concern about 1% of treated patients in clinical trials. However, the risk associated with VNR seems to be similar to that of other chemotherapeutic agents in the same indications.