Studies on amino acids and peptides-III. 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide,LR, as a new racemization free coupling reagent in peptide synthesis

The easily accessible 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, $\text{LR}$, has been reacted with salts of N-protected amino acids $\text{1}$ (Z-Gly-OH, Boc-Gly-OH, Boc-S-Ser(Bzl)-OH, Boc-S-Tyr(Bzl)-OH, Z-S-Arg(Z₂)-OH, and Z-S-Pro-OH), at room temperature in CH₂Cl₂ to give the intermediates $\text{2}$, mixed anhydrides. When $\text{2}$ is treated with two moles of a base and one mole of the salt of an amino acid ester $\text{3}$ (TosOH·H-Gly-OBzl, HCl·H-Gly-OBzl, HCl·H-Gly-OEt, and HCl·H-S-Phe-OtBu) at 0°C, the expected peptide $\text{4}$ is isolated in high yields. LR is also found to be a useful reagent in a fragment coupling between Z-Gly-S-Ala-OH and TosOH·H-S-Leu-OBzl). This tripeptide was tested by means of HPLC (deprotection and amino acid analysis according to Izumiya was not necessary), and no epimerization (<0.7 %) was observed.     

Spectrophotometric determination of thiourea in microgram quantities

Summary Copper(II) forms a stable colourless complex with thiourea. This property has been utilized to develop a Spectrophotometric method for the determination ofg quantities of thiourea. The complex absorbs in ultraviolet region and the determinations are carried out at 250 nm. The method permits the determination of thiourea from 10–60g with error not exceeding ± 1.0%.

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Zusammenfassung Kupfer(II) bildet mit Thioharnstoff eine farblosa Komplexverbindung, die sich auf Grund ihrer Absorption bei 250 nm zur spektrophotometrischen Bestimmung von Mikrogrammengen Thioharnstoff eignet. 10 bis 60g Thioharnstoff lassen sieh mit einem Fehler von höchstens ± 1,0% bestimmen.

     

Determination of geosmin and 2-methylisoborneol in water using solid-phase microextraction and gas chromatography-chemical ionisation/electron impact ionisation-ion-trap mass spectrometry

A method for the determination of geosmin and 2-methylisoborneol (MIB) in water by solid-phase microextraction (SPME) is presented. Various SPME fibre chemistries have been compared for their efficiency in extracting MIB from water. Extraction conditions including the extraction time and temperature have been optimised. A 30 ml water sample is extracted for 20 min at 60 degrees C using a divinylbenzene fibre, and the extract analysed by gas chromatography with ion-trap mass spectrometry detection. d5-Geosmin and d3-MIB are added as internal standards to compensate for any variability in the SPME process which is not carried out to equilibrium. Chemical ionisation, using acetonitrile as the reagent gas, was found to give superior sensitivity to electron impact ionisation (EI) for the detection of MIB. EI was used as the ionisation mode for detection of geosmin. The method shows good linearity over the concentration range 5-40 ng l-1 and gives detection limits of 1 ng l-1 for both geosmin and MIB. Recovery (93-110%) and precision (3-12%) over this concentration range, for both raw and treated drinking waters, are comparable to currently employed methods such as closed-loop stripping analysis (CLSA). The method offers the advantage of being simple to use, with much shorter analysis times in comparison to CLSA.     

Der chemische Transport von FeP2 und FeP4 mit lod

Chemical Transport of FeP₂ and FeP₄ with Iodine Experiments on the chemical transport of FeP₂ and FeP₄ with iodine are discussed, considering the gaseous molecules I₁, I₂, FeI₂, Fe₂I₄, FeI₃, Fe₂I₆, PI₃, P₂I₄, P₄, P₂, and P. Thermodynamic calculations give δH°(298) = 56.322 kcal and ΔS°(298) = 39.5 cal/K for the reaction FeP_2,f + I₂ = FeI₂ + 0.5 P₄ and δG°(923) = 35.8 kcal for the reaction FeP_4,f + I₂ = FeI₂ + P₄.     

Selective adhesion of endothelial cells to artificial membranes with a synthetic RGD-lipopeptide

A constrained cyclic ArgGly-Asp-D-Phe-Lys, abbreviated as cyclo(-RGDfK-), lipopeptide has been synthesized and incorporated into artificial membranes such as giant vesicles with DOPC and solid-supported lipid bilayers. The selective adhesion and spreading of endothelial cells of the human umbilical cord on solids functionalized by membranes with this RGD-lipopeptide have been observed. Furthermore, we have demonstrated strong selective adhesion of giant vesicles to endothelial cells through local adhesion domains by combined application of hydrodynamic flow field and reflection interference contrast microscopy (RICM). The adhesion can be inhibited by competition with a water-soluble RGD peptide. We suggest that this strategy could improve the efficiency of liposomes targeting used as vectors or as drug carriers to cells.     

Determination of testosterone in human hair by gas chromatography-selected ion monitoring mass spectrometry.

A method for the determination of testosterone in human hair by gas chromatography-mass spectrometry using d3-testosterone as internal standard is described. Our method consisted of alkaline digestion, fast liquid-liquid extraction, LH-20 chromatography and derivatization with heptafluorobutyric anhydride. Quantification was achieved by selected ion monitoring of m/z 680 (testosterone) and m/z 683 (d3-testosterone). Our method needed no complex corrections for isotope contributions. The procedure provided a sensitive and specific technique with good accuracy and precision. For the first time, testosterone has been quantified by gas chromatography-mass spectrometry in human hair. The concentrations (median, range, ng g-1 hair) reflected a significant (p = 0.05; t-test) sex difference with 2.7 ng g-1 (2.5-4.2) in male and 1.7 ng g-1 (1.0-3.4) in female hair.     

Die Kristall- und MolekülStruktur von N,N′-Bis-(trimethylsilyl)-oximidsäure-bis(trimethylsilyl)-ester

The Crystal and Molecular Structure of N,N′-Bis(trimethylsilyl) Oximidic Acid Bis (trimethylsilyl) Ester The X-ray structure analysis of the reaction product of oxalyl chloride with sodium bis(trimethylsilyl) amide formulated by PUMP and ROCHOW as N,N′-bis(trimethylsilyl) oximidic Acid bis (trimethylsilyl) ester shows that the suggested structure is correct for the solid state. The compound crystallizes in the space group P1 with a = 9.948(4), b = 6.612(3), c = 10.370(4) Å, α = 88.87(6), β = 116.95(4), γ = 98.23(6)°, and Z = 1. The molecule manifests symmetry 1 .     

Koexistenzbeziehungen,Darstellung und Eigenschaften ternärer Phasen im System Cu/Mo/O

Coexistence Relations, Preparation and Properties of Ternary Compounds in the System Cu/Mo/O The phase diagram of the ternary system Cu/Mo/O is presented at 773 K. The compounds CuMoO₄, Cu₃Mo₂O₉, Cu₄Mo₅O₁₇, Cu₆Mo₅O₁₈, Cu_4–xMo₃O₁₂, and Cu_xMoO₃ are found to be thermodynamical stable. The homogeneity range of Cu_4–xMo₃O₁₂ runs to x = 0.1–0.2. Single crystals of CuMoO₄ and Cu₃Mo₂O₉ were grown by chemical transport reactions with TeCl₄, Cl₂, HCl, and Br₂ as transport agent. The results were compared with thermochemical calculations. The decomposition of CuMoO₄ and Cu₃Mo₂O₉ was investigated with thermal analysis and decompositon pressure measurements.     

Enantiopure 4- and 5-aminopiperidin-2-ones: regiocontrolled synthesis and conformational characterization as bioactive beta-turn mimetics

Starting from aspartic acid, we synthesized lactam-bridged beta- and gamma-amino acid equivalents. Using the 1,4-bis-electrophile 1b as a central intermediate, the 4- and 5-aminopiperidin-2-ones 4 and 8, respectively, were approached by regioselective functionalization and subsequent lactamization. Diastereoselective C-alkylation was performed after N-protection of the lactam functionality when exclusive trans configuration resulting in the formation of 5a-f was observed in the 4-amino series. On the other hand, cis selectivity was typical for the alkylations of the 5-amino lactams 5a,b. To investigate the ability of the lactam building blocks to induce reverse-turn structures by intramolecular hydrogen bonding, the model peptidomimetics 12 and 14 representing Homo-Freidinger lactams of type II and III were prepared from 4a and 8a, respectively. Conformational analyses in dilute solution (1 mM) by IR and NMR spectroscopy at room temperature clearly indicated that the 4-aminopiperidin-2-one derivative 12 predominantly adopts a reverse-turn structure stabilized by a CO-HN hydrogen bond in an 11-membered ring. VT NMR experiments showed a substantial temperature dependency of the terminal NH when Deltadelta(NH)/DeltaT = -6.5 indicated that the amount of intramolecular hydrogen bonding is higher at low temperature. An application in the field of medicinal chemistry was demonstrated. Thus, starting from the Homo-Freidinger lactam 11c and the enantiomer ent-11c, we synthesized the peptidomimetics 15c and 16c and investigated them as lactam-bridged analogues of the dopamine receptor modulating peptide Pro-Leu-Gly-NH(2) (PLG). Both test compounds turned out to enhance significantly the agonist binding of dopamine D2 receptors, when the isomer 15c revealed a potency comparable to the genuine ligand PLG.     

Solid-phase synthesis of isoxazoles using vinyl ethers as chameleon catches

[reaction: see text] Regioselective 1,3-dipolar cycloadditions of supported vinyl ethers R(1)C(=CH(2))O-CH(2)-polymer, prepared by the Tebbe olefination of R(1)CO(2)-CH(2)-polymer, with ethyl cyanoformate N-oxide gave supported isoxazoline derivatives. Release from the support under mild acidic conditions gave the isoxazoles ethyl 5-R(1)-isoxazole-3-carboxylates. Alternatively, further on-resin functionalization of the R(1) substituent using Suzuki coupling reactions and release from the support under acidic conditions gave more structurally diverse isoxazoles.