A New Access to Piperidino-cyclopiperidinecarboxamides – constrained analogues of a pharmaceutical used diaminic building block

6-Piperidino-3-azabicyclo[3.1.0]hexane-6-carboxamide diastereomers 1a and 2a represent conformationally rigid analogues of 3a which is a building block in some pharmaceutical compounds. A new access to these compounds 1a and 2a was found via the cleavage of bicyclic N,N-acetal 6 with hydrocyanic acid as the stereodetermining step. Reaction of derivatives 1a and 2a with bromodiphenyl-butyronitrile 14 gave cyclopiritramide isomers 1c and 2c , respectively. Qualitative preliminary investigations showed different affinities of 1c and 2c to the opiate-μ receptor. These results were discussed on the basis of an X-ray structural analysis of cyclopiritramide isomer 2c . 1-Benzylcyclopiperidine derivatives 1d and 2d were used as model systems for studying the conformation of cyclopiritramide isomer 1c and 2c , respectively.     

ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.     

Diazoverbindungen. 72. (Diazoalkyl)phosphane – Synthese durch elektrophile Diazoalkansubstitution und oxidative Additionsreaktionen am Phosphor

Diazo Compounds. 72. Diazoalkylphosphanes – Synthesis by Electrophilic Diazoalkane Substitution and Oxidative Addition Reactions at Phosphorus Electrophilic diazoalkane substitution of the diazomethyl compounds 1a,b with the chloro phosphanes 2a-o in the presence of lithium diethylamide yields the diazoalkyl phosphanes 3a-z . Oxidative addition of oxygen, sulfur and selenium at phosphorus leads into the series of oxo, thioxo and selenoxo phosphanes having diazoalkyl substituents ( 4a-d, 5a-m and 7a-d ). The silyl group of 5n,o is cleaved by chromatography on aluminium oxide to yield the (diazomethyl)phosphane sulfides 6a,b .     

Measurements of the Refractive Index Increment on Hydroxyethyl Starch as a Basis for Absolute Molecular Weight Determinations

Solutions of hydroxyethyl starch are used as a blood plasma substitute. If their physiological efficiency is to be optimized, they need to be accurately characterized in terms of their molecular weight and its distribution. The absolute determination of molecular weight and molecular weight distribution by means of light scattering require a knowledge of the refractive index increment. Although numerous investigations of the refractive index increment of hydroxyethyl starch have already been published, the results vary significantly due to the use of different samples and the choice of different measuring parameters. There was therefore an urgent need to examine the extent to which the refractive index increment depends on molecular parameters, the experimental method used and the type of processing. Here it was found that different sample preparations result in different contents of solid matter, so that an exact determination of the quantity is required. Hydroxyethyl starches in the molecular weight range of about Mw = 200.000 g/mol and varying degrees of substitution between DS 0.38 and 0.50 which are regarded as optimal for clinical use give a refractive index increment of dn/dc^633nm = 0.146 = 0.005 cm³/g (solvent: H₂O/0.02% NaN₃; T = 25°C).     

Untersuchungen zu Mesityldimethylhalogensilanen als Schutzgruppenreagenzien für Alkohole

Investigation on Mesityldimethylhalosilanes as Protectiv Reagents for Alcohols The use of mesityldimethylhalosilanes as protecting reagents for steroid alcohols was investigated. The resistance of the obtained silyl ethers was tested in various media. The reaction pathway of the acidic hydrolyses of the silyl ethers is explained.     

Viscosity of glass-forming melt at the bottom of high-level waste melter-feed cold caps: Effects of temperature and incorporation of solid components

During the final stages of conversion of melter feed (glass batch) to molten glass, the glass-forming melt becomes a continuous liquid phase that encapsulates dissolving solid particles and gas bubbles that produce primary foam at the bottom of the cold cap (the reacting melter feed in an electric glass-melting furnace). The glass-forming melt viscosity plays a dominant role in primary foam formation, stability, and eventual collapse, thus affecting the rate of melting (the glass production rate per cold-cap area). We have traced the glass-forming melt viscosity during the final stages of feed-to-glass conversion as it changes in response to changing temperature and composition (resulting from dissolving solid particles). For this study, we used high-level waste melter feeds—taking advantage of the large amount of data available to us—and a variety of experimental techniques (feed expansion test, evolved gas analysis, thermogravimetric analyzer-differential scanning calorimetry, X-ray diffraction, and viscometer). Starting with a relatively low value at the moment when the melt connects, melt viscosity reached maximum within the primary foam layer and then decreased to its final melter operating temperature value. At the cold-cap bottom—the boundary between the primary foam layer and the thermal boundary layer—where physicochemical reactions of a melter feed influence the driving force of the heat transfer from the melt to the cold cap, the melt viscosity affects the rate of melting predominantly through its effect on the temperature at which primary foam is collapsing.     

Synthese von Heterocyclen durch C?C-Knüpfung. IV. Heterocyclensynthesen durch intramolekulare Dien-Reaktion

Synthesis of Heterocyclic Compounds by C C-bond Closure. IV. Synthesis of Heterocyclic Compounds by Intramolecular Dienreaction N-2-Cyclohexenyl-N-isopropylcinnamamide 8 cyclizes at 230°C to give the decahydronaphthindolone 9 . N-Alkyl-N-allylcinnamamides 10 analogously form 1 H-hexahydrobenzisoindolones 11 . N-Alkyl-N-allylsorbamides 14 cyclize at 150°C to 1 H-hexahydroisoindolones 15 . 15b yields the cyclic enamide 16 by alkali catalyzed shift of the double bond. Tricyclic lactames 19 and 20 are formed by thermal isomerization of N-cycloalkenylsorbamides 18a and 18b , respectively.     

Redox processes in pressurised smoked salmon studied by resonance Raman spectroscopy

Non-thermal food preservation technology is based on the application of high pressures up to 600 MPa. Here we report a resonance Raman (RR) spectroscopic analysis of smoked salmon meat after high pressure processing. High quality spectra, which can be obtained even from packed salmon without spectral interference of the packing foil, allow determining pressure-dependent irreversible changes of the main RR-active components of salmon meat, astaxanthin and myoglobin/haemoglobin. High pressure-treatment causes a decrease of the relative RR intensities of astaxanthin as probed with 514 nm excitation which is in line with a slight attenuation of the originally intense red colour of the salmon meat. 413-nm excited RR spectra indicate a heterogeneous broadening of astaxanthin bands accompanied by the formation of deoxy-myoglobin or deoxy-haemoglobin. The results suggest that pressure-treatment facilitates the oxidative degradation of astaxanthin coupled to the reduction of metmyoglobin (methaemoglobin).     

靴套的创新开发--QualiFlex靴套

对比了QualiFlex Q型,QualiFlex QX型、QualiFlex QV型三种聚胺酯材料靴套的性能,从而说明独特的QualiFlex靴套性能,使纸幅横幅水分的均匀性得到改善,纸幅出压榨干度得以维持恒定.