Determination of betamethasone and triamcinolone acetonide by GC-NCI-MS in excreta of treated animals and development of a fast oxidation procedure for derivatisation of corticosteroids.

The use of corticosteroids in combination with other hormonal substances has long been known to result in increased mass gain with bovines. Practice has demonstrated, however, that even the single use of a glucocorticoid may result in growth promoting effects. In addition to the popular dexamethasone, more recently other corticosteroids have also been misused for fattening purposes. The first part of this study deals with the detection of two of them, namely betamethasone and triamcinolone acetonide. Betamethasone was administered orally to a cow at a dose of 50 mg d-1 for 5 d, then later the same cow was injected intramuscularly with a dose of 50 mg of betamethasone dipropionate. Excretion in urine and faeces was followed with both HPLC-enzyme immunoassay and a previously described method based on negative chemical ionization mass spectrometry (NCI-MS) after oxidation. For the triamcinolone acetonide study a cow was treated with 50 mg d-1 of the drug during a 7 d period. Excretion in faeces was followed with GC-NCI-MS. As triamcinolone acetonide is resistant to the previously described oxidation procedure, however, a hydrolysis step had to be introduced prior to oxidation. In addition to this specific modification necessary for triamcinolone acetonide, in a subsequent part of this study the original oxidation procedure with pyridinium chlorochromate was re-investigated especially to shorten the procedure. With the introduction of potassium dichromate the reaction time could be decreased from 3 h to 10 min.     

Determination of sulphur in fly ash by instrumental proton activation analysis

A method for the determination of sulphur in fly ash by instrumental proton activation analysis using the³⁴S/p,n/^34mCl reaction was developed. The 2128.5 keV and 3305.0 keV -rays of^34mCl /t=32.0 min/ were measured on a Ge/Li/ -spectrometer, shielded with a lead absorber to attenuate low energy -rays. Irradiation and measuring conditions were optimized. The detection limit for instrumental analysis is 0.3 to 1 mg g^–1 and the standard deviation is cca. 4% for a typical sample.     

516—Synthetic and biological membranes

Biological cell membranes are compared to artificially produced permselective membranes. In spite of the difference in their thickness and electric resistance it is shown that they are similar in many important aspects, and the behaviour of synthetic membranes can explain very many points in the behaviour of cell membranes, especially axons. It is stressed that it is seldom necessary to assume unproven channels in biological membranes which are specific in the transport of a single ion species. Most of the phenomena of selectivity, opening and closing of such membranes can be explained by the influence of pH on membrane sites, by their poisoning with higly charged and/or large counter-ions. The borderline between two oppositely charged regions of a mosaic membrane opens up because it can be traversed by both positive and negative ions and permselectively is lost. Bipolar membranes rectify the current. Amphoteric membranes undergo very complex changes in conducting properties and permselectively with pH, especially when allowance is made for the weakly dissociated sites contained within these membranes. It is suggested that black lipid membranes made in the laboratory could be used to elucidate new points of similarity if they were used under similar conditions to our technical membranes.     

Synthesis of 3-carbomethoxy-3,4-dialkylcyclohexanones

The uncatalyzed 1,4-addition of phenylmagnesium bromide and furylmagnesium iodide to methyl 5-methoxy-1,5-cyclohexadienylcarboxylate ($\text{1}$), directly followed by alkylation and hydrolysis leads to the corresponding cyclohexanones of type $\text{2}$ (R₁ and R₂ trans) in moderate to high yield.     

Synthesis of coumarins by ring-closing metathesis using Grubbs’ catalyst

A novel generally applicable synthesis of coumarins from phenolic substrates utilizing ring-closing metathesis is described. This sequence involves O-allylation of phenols followed by ortho-Claisen rearrangement, subsequent based-induced isomerization affording 2-(1-propenyl)phenols, acylation with acryloyl chloride, and finally ring-closing metathesis (RCM) with Grubbs’ second generation catalyst.     

Relations entre structure chimique et grandeurs de retention. VII. Composés de structure cyclopropanique

Résumé Les auteurs ont étudié le comportement chromatographique sur plusieurs phases stationnaires polaires et non polaires de composés cyclopropaniques stéréoisomêres: où R=H ou CH₃ et X=CH, COOCH₃ ou CH₂OH. Les résultats sont interprétés en fonction de la configuration de X par rapport à , de la nature électronique de X et de l'orientation du phényle par rapport au plan du cyclopropane.

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Relationship between chemical structure and retention. VII. Cyclopropane compounds

Summary The chromatographic behaviour, on several polar and non polar phases, of stereoisomeric cyclopropanes has been studied R=H or CH₃ and X=CN, COOCH₃, CH₂OH. The results are interpreted in terms of the X versus configuration, the electronic nature of X and the orientation of the phenyl ring in relation to plane of the cyclopropane ring.

     

Synthesis of 6R(β)-tritylaminopenicillanic-3R(β)-alcohol,a versatile stereoisomer of natural β-lactams

In an attempt to rationalize a synthesis of penicillin analogs modified at C(3), we have isolated the 3R(β)-carbinolamide derivative 4a. The trityl substituent on N(6′) seems to be responsible for the inversion of configuration which occurs at C(3) during the acid hydrolysis of the isocyanate intermediate. An hydrogen bond is formed on the β-face of the bell-shaped bicyclic skeleton between the N(6′)-nitrogen lone pair and the C(3) hydroxyl group. On standing, the carbinolamide analog slowly isomerizes to its expanded bicyclic isomer 4b , but the starting material may be easily recovered by treatment with acid. The postulated intermediate during isomerization, i.e., the open aldehyde form, does not accumulate. Substitutions of the hydroxyl group at C(3) lead to a variety of compounds with the biologically active 3S(α) configuration. These may be used to study the importance of the carboxyl group of penicillins in their interaction with β-lactamases at the molecular level.     

Isolation of pure (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine from Blighia sapida (Akee)

The isolation of (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (CCG I, 2) from Blighia sapida (Akee) was achieved through column chromatography on deactivated silica gel followed by ion-exchange chromatography. A HPLC method has also been devised in order to assess the purity of the isolated product.     

A new synthesis of hydroxyphthalides

Cyclization of suitable enamino ketones can produce hydroxyphthalides.     

Thermal decomposition of dicyclopentadienylarylvanadium compounds

The thermolysis of compounds of the type Cp₂VR (R = aryl) in the solid state has been studied. A distinct increase in thermal stability is observed upon substitution of the ortho-position of the aryl group. Thermal decomposition occurs with formation of RH, Cp₂ V, a vanadocene homologue with the group R substituted in one of the Cp rings and, probably, a vanadocene homologue with two substituted Cp rings. It is shown that the abstraction of the hydrogen atom from the cyclopentadienyl ring, necessary for the formation of RH, is an intermolecular process, whereas the substitution of the aryl group in the Cp ring is intramolecular. A decomposition mechanism is proposed in which the group R is transferred from the vanadium atom to the C₅H₅ ring of the same molecule by interaction with an aryl group of another molecule. The thermal decomposition of Cp₂VR is compared with that of the analogous titanium compounds.