Use of enyne compounds in the synthesis of insect pheromones

A new approach has been developed to the synthesis of monogenic insect pheromones with acetogenin and macrolide structures, using the low reactivity of ozone and of 9-borabicyclo[3.3.1]nonane towards an acetylenic function as compared with a vinyl function.Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences. Translated from Khimiya Prirodnykh Soedinenii, Vol. 33, No. 1, pp. 34–41, January–February, 1997.     

The analysis of pharmaceutical compounds using electrochromatography

Chromatographia - Electrochromatography couples the very high efficiencies associated with capillary zone electrophoresis, with reversed-phase liquid chromatography (RPLC). Therefore,...     

Solid-state of pharmaceutical compounds

This article summarizes the different steps needed for a proper design and monitoring of the solid-state in pharmaceutical industry in order to fulfill the requirements of the guideline dealing with polymorphism of the International Conference of Harmonization. This revised version was published online in July 2006 with corrections to the Cover Date.     

A process in need is a process indeed: scalable enantioselective synthesis of chiral compounds for the pharmaceutical industry

This report deals with enantioselective synthesis of viracept 1 (nelfinavir mesylate, AG 1343), a potent HIV protease inhibitor, and 3-hydroxytetradecanoic acid 3, a component of lipid A comprising lipopolysaccharide embedded in the cell surface of Gram-negative bacteria, from both strategic and practical perspectives. As regards the synthesis of 1, the synthetic approaches to its central intermediate 2 possessing the common structural motif of 1,4-differentially substituted-2-amino-3-hydroxylbutane are mainly discussed with emphasis on the molecular symmetry that has helped streamline the synthetic strategy. In the discussion of the synthetic strategies to access a single enantiomer of 3, the chiral methodologies that have been applied so far are assessed for industrial viability; the synthetic alternatives explored include resolution via diastereomeric salt formation, lipase-catalyzed kinetic resolution, asymmetric synthesis, and chiral pool approaches.     

Aqueous electrosynthesis of carbonyl compounds and the corresponding homoallylic alcohols in a divided cell

An aqueous paired electrosynthesis is studied in a divided cell. On graphite anode Br⁻ was oxidized to Br₂ and this generated Br₂ oxidized alcohols to the corresponding carbonyl compounds while Sn²⁺ was reduced to Sn⁰ on graphite cathode. Then the produced metallic tin mediated allylation of the carbonyl compounds with allyl bromide to generate the corresponding homoallylic alcohols. In the reaction the mediators (Sn and Br₂) were generated in situ and could be reused via the electrolysis. Both working electrode and the counter electrode were utilized to generate useful products without the sacrifice of the electrode materials.     

Facile synthesis of novel heterocyclic compounds based on pyridine moiety with pharmaceutical activities

A novel run of fused heterocyclic derivatives containing pyridine moieties has been disclosed by allowing 2-amino-4-phenyl-6-(phenyl amino)pyridine-3,5-dicarbonitrile 1 to undergo annulation reactions with different reagents. Most of synthesized compounds have moderate to strong antitumor activity against HePG-2 and MCF-7. Moreover, MOE 2014.09 software was used to run the computational studies to support the biological activity results. The assigned structures for all the newly prepared derivatives were ascertained on the basis of elemental analyses and spectral data.     

Thermal analysis of pharmaceutical compounds

Some sulphonamides are evaluated by means of thermal analysis. Use is made of their characteristic endothermic DTA peaks (melting peaks), where the area changes linearly with variations in the amount of sulphonamides. The method is suitable for the determination of 30–100 mg of sulphathiazole, sulphisomidine, sulphaguanidine, sulphacetamide sodium and sulphamethoxypyridazine with reasonable accuracy. As for sulphisoxazole, two peaks are used for its determination: an endothermic one to determine 30–100 mg, and an exothermic one to determine 6–30 mg.

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Zusammenfassung Einige Sulphonamide wurden durch thermische Analyse bestimmt, wobei von der linearen Abhängigkeit der Fläche der charakteristischen endothermen DTA-Peaks (Schmelzpeaks) von der Menge der Sulphonamide Gebrauch gemacht wurde. Mit der Methode können 30–100 mg Sulphathiazol, Sulphisoimidin, Sulphaguanidin, Natrium-Sulphacetamid und Sulphamethoxypyridazin mit ausreichender Genauigkeit bestimmt werden. Bei der Bestimmung von Sulphisooxazol wurde ein endothermer Peak für Mengen von 30–100 mg und ein exothermer für geringere Mengen von 6–30 mg herangezogen.

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Thermal analysis of pharmaceutical compounds

The thermal behaviour of some antiallergic drugs belonging to different groups of antihistaminics, such as phenyltoloxamine, chlorpromazine, clemizole and meclozine was examined. Thermogravimetry, derivative thermogravimetry and differential thermal analysis curves were used for the elucidation of the mechanisms of thermal decomposition. The melting temperatures of the compounds and their thermal stabilities were determined. The stability was found to decrease in the order: clemizole > chlorpromazine > meclozine > phenyltoloxamine.The kinetic parameters of the thermal reactions were calculated and their values are in accordance with the results obtained, especially those of the stability.Infrared spectroscopic analysis of the compounds together with their thermal decomposition products was performed in order to establish the possible sites of decomposition.

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Zusammenfassung Das thermische Verhalten einiger, verschiedener Antihistaminika angehörender antiallergetischer Arzneimittel, wie Phenyltoloxamin, Chlorpromazin, Clemizol und Meclozin wurde untersucht. Die Methoden der Thermogravimetrie, derivativen Thermogravimetrie und Differentialthermoanalyse wurden zur Klärung des Mechanismus der thermischen Zersetzung eingesetzt. Die Schmelztemperaturen der Verbindungen und ihre Thermostabilität wurden bestimmt. Es zeigte sich, dass die Stabilität in der Reihenfolge Clemizol > Chlorpromazin > Meclozin > Phenyltoloxamin abnimmt.Die kinetischen Parameter der thermischen Reaktionen wurden berechnet und ihre Werte, besonders die der Stabilität, sind in Übereinstimmung mit den erhaltenen Ergebnissen.Die infrarotspektroskopische Analyse der Verbindungen erfolgte zusammen mit der ihrer thermischen Zersetzungsprodukte um die möglichen Zerfallsbereiche zu ermitteln.

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Résumé On a étudié le comportement thermique de quelques médicaments antiallergiques appartenant aux différents groupes des antihistaminiques, comme la phényltoloxamine, la chlorpromazine, la clémizole et la méclozine. On s'est servi des courbes thermogravimétriques, de leurs dérivées ainsi que des courbes d'analyse thermique différentielle pour élucider le mécanisme de la décomposition thermique. On a déterminé les températures de fusion et la stabilité thermique des composés. On a trouvé que la stabilité diminue dans l'ordre suivant: clémizole > chlorpromazine > méclozine > phényltoloxamine.On a calculé les paramètres cinétiques des réactions thermiques; leurs valeurs, en particulier celles de la stabilité, sont en accord avec les résultats obtenus.Les composés de départ et leurs produits de décomposition thermique ont été examinés par spectroscopie infrarouge afin de trouver les sites possibles de décomposition.

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Thermal analysis of pharmaceutical compounds

Fourteen sulphonamides have been thermally analyzed using thermogravimetry (TG), derivative thermogravimetry (DTG) and differential thermal analysis (DTA). Their thermal reactions and stabilities have been thoroughly studied. It was found that the sulphonamides are first transformed into sulphanilamide. The melting points of these sulphonamides have been determined through their DTA curves and by the Kofler microscope, the results agreeing with those reported in the literature. The amount of water of crystallization has been calculated from the TG and DTG curves. Analysis of mixtures of some sulphonamides has been achieved by thermal analysis and by thin-layer chromatography using different solvent systems.

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Zusammenfassung Vierzehn Sulfonamide wurden unter Anwendung der Thermogravimetrie (TG), der derivativen Thermogravimetrie (DTG) und der Differentialthermoanalyse (DTA) thermisch analysiert. Die thermischen Reaktionen und Stabilitäten wurden untersucht. Es zeigte sich, daß die Sulfonamide zuerst in Sulfanilamide umgewandelt werden. Die Schmelzpunkte der Sulfonamide wurden über ihre DTA-Kurven und mit dem Kofler-Mikroskop bestimmt, die Ergebnisse stimmten mit den in der Literatur angegebenen überein. Die Menge des Kristallwassers wurde aus den TG- und DTG-Kurven berechnet. Die Analyse von zwei, drei und vier Sulfonamiden wurde durch Thermische Analyse und Dünnschichtchromatographie unter Anwendung verschiedener Lösungsmittelsysteme durchgeführt.

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Résumé Quatorze sulfonamides ont été examinés par thermogravimétrie (TG), thermogravimétrie différentielle (TGD) et analyse thermique différentielle (ATD). Leurs réactions thermiques et leurs stabilités ont été étudées d'une manière approfondie. On a trouvé que les sulfonamides se transforment d'abord en sulfanilamides. Les points de fusion des sulfonamides ont été déterminés à partir de leurs courbes ATD et avec le microscope Kofler; les résultats ont concordé avec ceux de la littérature. La teneur en eau de cristallisation a été calculée à partir des courbes TG et TGD. L'analyse de deux, trois et quatre sulfonamides a été effectuée par analyse thermique et Chromatographie en couches minces avec différents solvants.

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Thermoanalytical methods in pharmaceutical technology

A short survey is given of some aspects of the application of thermoanalytical methods, especially differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermogravimetry (TG), in solid-dosage technology. The usefulness of these methods in the prediction of drug-excipient compatibility, studies of solid-dispersion systems, the analysis of enantiomers and racemates, measurement of the time of tablet disintegration, the analysis of drug formulations and studies of the processes of grinding and drying of drugs is discussed.

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Zusammenfassung Es wird ein kurzer Überblick über einige Aspekte der Anwendung von thermoanalytischen Methoden, insbesondere von DTA, DSC und TG in der Feststoffdosierung gegeben. Weiterhin wird die Nützlichkeit dieser Methoden bei der Voraussage der Bindemittelverträglichkeit, bei der Untersuchung disperser Feststoffsysteme, bei der Analyse von Enantiomeren und Racematen, bei der Messung der Tablettenzerfallszeit, bei der Analyse der Arzneimittelformierung und bei der Untersuchung von Mahl- und Trocknungsprozessen bei Arzneimitteln diskutiert.

     

Multi-residue analysis of pharmaceutical compounds in aqueous samples

Pharmaceutical compounds are nowadays an emerging group of organic pollutants in aquatic systems. Several methodologies have already been published to measure these pollutants in the environment, showing the difficulties to take into account the various compounds belonging to numerous therapeutical and chemical groups. In order to develop environmental monitoring, there is a need for a less costly and time-consuming multi-component procedure. The work presented here deals with the development of an extraction procedure which enables the measurement of a wide spectrum of pharmaceuticals at trace levels (ng 1(-1)) with quite simple equipment (i.e. GC-MS with single quadruple as analyzer). The analyzed compounds comprise anti-inflammatories, antidepressants and hypolipidic drugs. The reliability and sensitivity have been tested on 18 different compounds (7 basic compounds and 11 acidic drugs) extracted simultaneously and analyzed by GC-MS. The optimized procedure has been successfully applied to the analysis of wastewaters, surface waters and drinking waters from the following areas: first the Cortiou rocky inlet, in the Mediterranean Sea (South coast of France), highly impacted by the Marseilles wastewater treatment plant effluent and secondly the Hérault watershed by studying drinking water, surface water and wastewater. In both cases, the level of pharmaceuticals was totally unknown. Results obtained have demonstrated the suitability of the method for multi-residue analysis of different types of water matrices.     

The combinatorial synthesis of organophosphorus compounds

The primary literature concerning the combinatorial synthesis of organophosphorus compounds is reviewed and discussed. The subject matter is divided into three main sections describing the solid phase, solution phase and solvent-free synthesis of phosphorus containing organic molecules. The review covers the synthesis of compounds in which the final products contain phosphorus-carbon bonds, primarily phosphonates, phosphinates, phosphine oxides and phosphines.     

Capillary electrochromatography of basic compounds in pharmaceutical analysis

Capillary electrochromatography (CEC) shows promising results in the separation of basic drugs. Traditional reversed-phase systems, with or without amine additives to the mobile phase to improve peak shapes, are the most commonly employed. Alternative useful stationary phases, such as strong cation exchangers and polymer-based continuous beds, are also discussed, as are methods to improve sensitivity by sample preconcentration. So far, studies performed on CEC have mainly been fundamental, but the technique is rapidly maturing and has many potential applications in the pharmaceutical field.     

The cleavage of heterocyclic compounds in organic synthesis II Use of 5‐nitroisatine for synthesis of various nitrogenous heterocycles

The reactions of 5‐nitroisatine were studied with nucleophiles like heterocyclic amines and alkaline hydroxide. With the use of alkaline hydroxide it was converted into 2‐amino‐5‐nitrophenylglyoxylic acid 2 , with piperidine, morpholine and carbethoxypiperazine to its amides 4a‐4c or by oxidation to 5‐nitroanthranilic acid 7. This acid was used for synthesis of 3‐hydroxy‐6‐nitro‐2‐phenyl‐1H‐quinolin‐4‐one 10. Semicarbazone of 5‐nitroisatine 11 was converted to 5‐(2‐amino‐5‐nitrophenyl)‐2,3,4,5‐tetrahydro‐1,2,4‐triazine‐3,5‐dione 12. Cyclocondensation of this compound to afford 8‐nitro‐2,3‐dihydro‐5H‐[1,2,4]triazino‐[5,6‐b]indol‐3‐one 13 was unsuccessful.     

The Grandberg reaction in the synthesis of biologically active compounds

The review is focused on the Grandberg synthesis, namely, the synthesis of tryptamines from arylhydrazines and γ-halocarbonyl compounds, as an exceptionally useful and efficient methodology to access biologically active indole heterocycles.     

Room-temperature fluorescence spectrometry of some pharmaceutical compounds

Room-temperature fluorescence of 66 pharmaceutical drugs are presented using a mixture of ethanol/water as solvent. The analytical figures of merit for the fluorescent species are reported with limits of detection ranging between 1 and 30 ng/ml for most of them and with average blank standard deviation of 7.6%. The spectral band half-widths are also reported.     

Thermal stability and decomposition of pharmaceutical compounds

Thermal analysis of fusion and decomposition processes were carried out on recently synthetized pharmaceutical compounds in order to establish thermal stability criteria. This study was carried out using thermogravimetry, TG, and differential scanning calorimetry, DSC. Degradation and fusion temperatures have been produced as thermal data with the aim of to study the thermal stability of the compounds. Relationship is found among stability and a series of effects of structure of the compounds. The compounds which present an amide functional group in the central molecule are more stable because they have a comparatively higher fusion and degradation temperature. In addition, the stability of this type of compounds depends on the position of the electrophilic substitution (in ortho, meta or para). Likewise, the groups linked to the aromatic ring with high electronic density give stability, and therefore are able to delocalize the charge in a greater spacial interval. Therefore, criteria for the selection of substituents have established that improve the stability of compounds     

The use of umbelliferone in the synthesis of new heterocyclic compounds

New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one, 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol-2(3H)-one, 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N-phenylhydrazinecarbothioamide, 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one and 7-[(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methoxy]-2H-chromen-2-one were prepared starting from the natural compound umbelliferone. The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR).