A sequential reaction process to assemble polysubstituted indolizidines, quinolizidines and quinolizidine analogues

The ω-iodo-α,β-alkynoates and their ketone, sulfone or phosphonate analogues react with δ-chloropropylamines in MeCN assisted with K₂CO₃ to undergo a sequential S_N2/Michael addition/S_N2/S_N2 reaction process, giving polysubstituted indolizidines or quinolizidines in good to excellent yields. This sequential reaction process is also compatible with three other substituted α,β-alkynoates, affording quinolizidine analogues in moderate to good yields.     

High performance liquid chromatographic determination of metoclopramide in plasma and urine and its application to biopharmaceutical investigations

An optimized HPLC method for the quantification of metoclopramide (MCP) in human plasma and urine is described. MCP and internal standard are extracted from alkalinized substrate into diethyl ether and back-extracted into dilute acid. The analytes are separated with a ternary mobile phase at cyanopropyl-silica and detected at 312 nm (UV detection). The lower limit of quantification is 0.5 ng/ml in plasma and 50 ng/ml in urine. Optimization of extraction, chromatography, and detection is discussed. The method is selective to numerous common drug substances with excellent accuracy and precision data. After validation, the method is applied to the samples of a pharmacokinetic study. Pharmacokinetic parameters indicate the need for a sophisticated method as tool for optimization of metoclopramide formulations.     

Coordination around thorium(IV) in aqueous perchlorate,chloride and nitrate solutions

The coordination around the thorium(IV) ion in aqueous perchlorate, chloride and nitrate solutions has been determined from large angle X-ray scattering measurements. In perchlorate solutions, where inner-sphere complexes are not formed, the first coordination sphere contains 8.0±0.5 water molecules with Th-H₂O bond lengths of 2.48₅ Å. In chloride solutions inner-sphere complexes are formed, which lead to an increase in the coordination number. In nitrate solutions the nitrate ions are bonded as bidentate ligands to the thorium ion. The bond lengths are similar to those found in crystalline hydrates of thorium nitrate. The coordination numbers found for thorium(IV) in solution are compared with previously reported values for lower charged ions of similar size.On leave from Department of Inorganic Chemistry Royal Institute of Technology S-10044 Stockholm Sweden     

Effect of H2S-uptake on the conversion of cyclohexene on Ru- and Pd-promoted molybdena-alumina catalysts

The effect of H₂S on the activity and selectivity of catalysts (Ru/Al₂O₃, Pd/Al₂O₃ and Ru and Pd promoted molydena-alumina) was different (on differnt catalysts and different conversions of cyclohexene). Ru-containing catalysts showed higher sulfur sensitivities than the Pd-containing ones. The sequence of catalysts by their H₂S uptake related to mass of catalyst was PdMo/Al₂O₃RuMo/Al₂O₃Mo/Al₂O₃>Pd/Al₂O₃Ru/Al₂O₃.     

Darstellung und spektroskopische Charakterisierung von Di(halogeno)phthalocyaninato(1–)rhodium(III), [RhX2Pc1−] (X = Cl,Br, I)

Synthesis and Spectroscopical Characterization of Di(halo)phthalocyaninato(1–)rhodium(III), [RhX₂Pc^1?] (X = Cl, Br, I) Bronze-coloured di(halo)phthalocyaninato(1–)-rhodium(III), [RhX₂Pc^1?] (X = Cl, Br) and [RhI₂Pc^1?] · I₂ is prepared by oxidation of (ⁿBu₄N)[RhX₂Pc^2?] with the corresponding halogene. Irrespective of the halo ligands, two irreversible electrode reactions due to the first ringreduction (E_R = ?0,90 V) and ringoxidation (E_O = 0,82 V) are present in the cyclovoltammogram of (ⁿBu₄N)[RhX₂Pc^2?]. The optical spectra show typical absorptions of the Pc^1?-ligand at 14.0 kK and 19.1 kK. Characteristic vibrational bands are at 1 366/1 449 cm^?1 (i. r.) and 569/1 132/1 180/1 600 cm^?1 (resonance Raman (r. r.)). The antisym. (Rh? X)-stretching vibration is observed at 294 cm^?1 (X = Cl), 240 cm^?4 (Br) and 200 cm^?1 (I). Only the sym. (Rh? I)-stretching vibration at 133 cm^?1 is r. r. enhanced together with a strong line at 170 cm^?1, which is assigned to the (I? I)-stretching vibration of the incorporated iodine molecule. Both modes show overtones and combinationbands.     

Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 2-, 3-, 4-, 5-, 6-and 7-chloro and bromo analogues

Summary A study was made of the fungitoxicity of 2-, 3-, 4-, 5-, 6- and 7-chloro and bromo-8-quinolinols againstAspergillus niger,A. oryzae,Myrothecium verrucaria,Trichoderma viride andTrichophyton mentagrophytes in Sabouraud dextrose broth and in Yeast Nitrogen Base supplemented with 1%D-glucose and 0.088%L-asparagine. Based on the presence or absence of synergism between pairs of substituted 8-quinolinols and reversal or nonreversal of toxicity byL-cysteine or N-acetyl-L-cysteine, the following conclusions were reached: (1) substituents on the quinoline ring change the site(s) of action of the toxicant; (2) the sites of action of the 5-, 6-, and 7-chloro-8-quinolinols are different from each other and from 8-quinolinol and its 2-, 3-, and 4-chloro analogues, and the same is true for the corresponding bromo compounds; (3) 8-quinolinol and its 3- and 4-chloro and bromo analogues appear to share common sites of action; (4) for good antifungal activity the 2 position of the ring must not be substituted by sterically bulky groups; (5) the geometry of the binding sites of action are not so constrained that they cannot accommodate the analogously substituted chloro- and bromo-8-quinolinols.

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Nachweis sterischer Faktoren bei der Fungitoxizität von 8-Chinolinol und seinen 2-, 3-, 4-, 5-, 6- und 7-Chlor- und -Brom-Analogen

Zusammenfassung Es wurde eine Studie der Fungitoxizität von 2-, 3-, 4-, 5-, 6- und 7-Chlor- und-Brom-8-chinolinol gegenüberAspergillus niger,A. oryzae,Myrothecium verrucaria,Trichoderma viride undTrichphyton mentagrophytes in Sabouraud Dextrose Nährmedium und in Hefe-N-Base mit 1%D-Glucose und 0.088%L-Asparagin unternommen. Auf der Basis des Zutreffens oder der Abwesenheit eines Synergismus zwischen Paaren von substituierten 8-Chinolinolen und der Umkehrung oder Nichtumkehrung der Toxizität durchL-Cystein oder N-Acetyl-L-cystein wurden folgende Schlußfolgerungen abgeleitet: (1) Substituenten am Chinolin-Ring ändern die Aktionsstelle(n) des Toxikans; (2) Die Angriffsstellen der 5-, 6- und 7-Chlor-8-chinolinole sind untereinander und von 8-Chinolinol und seinen 2-, 3- und 4-Chlor-Analogen verschieden, wobei das auch für die entsprechenden Brom-Verbindungen gilt; (3) 8-Chinolinol und seine 3- und 4-Chlor- und -Brom-Analogen scheinen gemeinsame Aktionsstellen zu teilen; (4) für eine gute antifungale Aktivität darf die 2-Position des Rings nicht mit sterisch anspruchsvollen Gruppen besetzt sein; (5) Die Geometrie des Bindungsstellen der Wirkung ist nicht so gespannt, daß nicht sowohl analoge Chlor- oder Brom-8-chinolinole Platz finden.

     

Synthesis of bis(cyclopentadienyl)diazadiene complexes of ytterbium. An X-ray structural study of the Cp2Yb(μ-η2:Ti2-But-N=CH-CH=N-But)Li(DME) complex

Ytterbium complexes, Cp₂Yb(-₂:²-DAB)Li(DME) (1) and CpYb(DAB)K(THF)₂ (2), containing a bridging diazadiene ligand were prepared by the reaction of CpYbCl₂(THF)₃ with (DAB)Li₂ (11) and (DAB)^–K⁺ (12) (DAB = Bu^t-N=CH-CH=N-Bu^t). The structure of complex1 was established by X-ray diffraction analysis. The complex is binuclear: the Yb atom of the Cp₂Yb fragment and the Li atom, which is bonded as well with the chelating DME molecule, are linked by the DAB ligand.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 148–151, January, 1994.     

Spektroskopische Eigenschaften von Di(phthalocyaninato)metallaten(III) der Seltenen Erden. Teil 2: Die Multikern(1H-, 13C-, 15N-, 17O- und 31P)-NMR-Spektren und Nachweis komplexgebundenen Wassers

Spectroscopical Properties of Di(phthalocyaninato)metalates(III) of the Rare Earth Elements. Part 2: The Multinuclear (¹H, ¹³C, ¹⁵N, ¹⁷O, and ³¹P) NMR Spectra and Determination of Complex Bound Water The ¹H, ¹³C, ¹⁵N, ¹⁷O and ³¹P NMR spectra of (PNP)[Ln(Pc^2?)₂] and (TDOA)[Ln(Pc^2?)₂] (Ln = La …? (—Pm) …? Lu); PNP: di(triphenylphosphine)-iminium; TDOA: Tri(n-dodecyl)n-octylammonium dissolved in CD₂Cl₂ are reported. With the exception of the nitrogen atoms of the cations all light atoms of both homologues complex salt rows have been detected and assigned. Proof of the presence of additional water contained in the (solid) complex salts has been given unambigously. The otherwise strong Fermi contact interactions diminuish rapidly with growing distance from the paramagnetic centre favouring dipolar (pseudo-contact) interactions. As a consequence the mostly element independent paramagnetic shifts of the atoms situated on the periphery of the anion as well as those of the cations and water are determined by the distance factor. Therefore a first glance of the structure of the ion-pair present in solution emerges, in which the water molecule seems to play an important role.     

Glykosylazide als Ausgangsbasis zur Gewinnung von Nucleosidanalogen, 3. Mitt. Synthese von Alkylaminotetrazol- und Uretidinonnucleosiden

The -ribofuranosylazide1 is transformed after usual derivatization by suitable protecting groups into the P–N-ylid2, which gives the corresponding N-Glykosyl-N-alkylcarbodiimides4 and a small amount of the glykosylisocyanatde-rivative3 by reaction with alkylisocyanates. The carbodiimides4 were reacted with hydrazoic acid to give the alkylaminotetrazolnucleosides5 and finally the free nucleosidanalogs6. In the case of5 c the 5-aziridinyltetrazolnucleosid5 h was formed by an usual neighbouring group reaction. In addition the compound1 is transformed into the 3,5-diprotected anchor derivative7 by reaction withTIPSCl₂. The latter could be transformed by usual steps into the alkylaminotetra-zolnucleosides8 with a free 2-OH group. In the next step the 2-p-tolylthiocarbo-nates9 were prepared followed by transformation to the 2-desoxynucleosides10 by means of tributyltinhydride. Finally the free 2-desoxynucleosides11 were prepared. By reacting the carbodiimides4 with phenylisocyanate a mixture of the two possible regiouretidinonnucleosidderivatives12 and13 are formed. In the case of the N-glykosyl-N-allylcarbodiimide4 d only the one isomer13 d arises.

Herrn Prof. Dr.A. Neckel mit den besten Wünschen zum 60. Geburtstag gewidmet.     

Characteristics of immunosorbents used as a new approach to selective solid-phase extraction in environmental analysis

Summary The trace-level determination of organic pollutants in complex matrices is difficult and often not reliable because theccurrent extraction procedures are non-selective. New extraction sorbents involving antigen-antibody interactions, called immunosorbents (ISs), have been synthesised in order to trap a group of structurally related pollutants. The IS capacity is always high for the analyte-antigen used to make the antibodies, but can be low for some related compounds. In this work, we show the relationship that exists between capacity, break-through volume and recovery of analytes because of the competition between the structurally related compounds for antibody sites. Breakthrough due to the overloading of the column should be avoided because calibration curves are no longer linear. The capacity of two ISs, one made for trapping the triazine pesticide group and the second for the phenylurea, group, have been optimised by selecting silica with 50 nm pore size. Calibration curves are linear for all the compounds in a mixture of ten phenylureas up to a concentration of 5 to 10 μg L⁻¹ for each compound when handling 50 mL water samples through a precolumn packed with 0.22 g of IS. Under these conditions, reliable quantitative results are obtained because calibration curves are similar when compounds are alone or in a mixture. Application to the clean-up of soil extracts illustrates the high selectivity and the high potential of these new sorbents in environmental analysis. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996