Synthèse asymétrique de pipéridines trifluorométhylées

In this manuscript is proposed a novel method to elaborate saturated N-heterocycles possessing a trifluoromethyl (Tfm) group at -position. These fluoro-organic compounds are attractive targets, due to their high potential interest for pharmaceutical and as well for agrochemical industry. By using a methodology developped at Laboratory, based on an intramolecular Mannich type reaction of -aminoketals, we could prepare a wide range of original Tfm-piperidine based structures. First of all we applied this methodology for the diastereoselective synthesis of Tfmpiperidines. -aminoketals synthons were easily obtained by the conjugated addition of phthalimide on required enones, followed by keto-protection and then hydrazinolysis. These key intermediates were submitted to Mannich intramolecular reactions with various aldehydes, giving a stereoselective access to triluoro-analogues of naturally occuring piperidine as well as some new 4-aza- and 4-hydroxy- Tfm-piperidines scaffolds. An enantioselective version of this strategy was then successfully carried out, starting from enantio-enriched -aminoketals prepared from a fluorinated oxazolidine (FOX) by a Mukaiyama-Mannich type reaction. Employment of these new enantio-enriched amines under identical cyclization conditions with different aldehydes furnished a variety of enantiopure Tfmpiperidines. This strategy was then validated by the first asymmetric synthesis of trifluoromethyl analogues of pipecolic acids, Tfm-piperidine based analogues of -aminobutyric acid (GABA) and polycyclic structures, as indolizidines, bearing a trifluoromethyl group.Dans ce manuscrit est proposée une méthode originale pour élaborer des N-hétérocycles saturés possédant un groupe trifluorométhyl (Tfm) en position alpha. Ces composés fluoro-organiques sont des cibles attrayantes, dues à leur intérêt potentiel élevé pour l'industrie pharmaceutique ainsi que pour l'agrochimie. En employant une méthode développée au laboratoire, basée sur une réaction de type Mannich intramoléculaire des béta-aminocétals sur des dérivés carbonylés, nous avons préparé un éventail de structures pipéridiniques originales. Tout d'abord nous avons appliqué cette méthodologie pour la synthèse diastéréosélective des Tfm-pipéridines. Les béta-aminocétals nécessaires à cette étude ont été facilement obtenus par l'addition conjuguée du phtalimide sur les énones correspondantes, suivi d'une céto-protection et d'une hydrazinolyse. Ces intermédiaires ont été soumis aux réactions de Mannich intramoléculaires avec divers aldéhydes, donnant ainsi un accès stéréosélectif aux analogues trifluorés de la pipéridine naturelle. Des réactions chimiques sur ces composés ont également permis la synthèse de nouveaux substrats tels que les 4-aza et 4-hydroxy Tfm-piperidines. Une version énantiosélective de cette stratégie alors a été réalisée avec succès au départ de béta-aminocétals énantiomériquement enrichi, préparés à partir d'une oxazolidine fluoré (FOX) par une réaction de type Mukaiyama-Mannich. L'emploi de ces nouvelles amines énantio-enrichies dans des conditions identiques de cyclisation avec différents aldéhydes a fourni une série de Tfm-pipéridines enantiopure. Cette stratégie a été validée par la première synthèse asymétrique des analogues trifluorométhylés des acides pipécoliques, des analogues l'acide gamma-aminobutyrique (GABA) et des structures polycycliques comme les indolizidines, contenant un groupe trifluorométhyle

Synthèse asymétrique de pipéridines trifluorométhylées

Dans ce manuscrit est proposée une méthode originale pour élaborer des N-hétérocycles saturés possédant un groupe trifluorométhyl (Tfm) en position alpha. Ces composés fluoro-organiques sont des cibles attrayantes, dues à leur intérêt potentiel élevé pour l'industrie pharmaceutique ainsi que pour l'agrochimie. En employant une méthode développée au laboratoire, basée sur une réaction de type Mannich intramoléculaire des béta-aminocétals sur des dérivés carbonylés, nous avons préparé un éventail de structures pipéridiniques originales. Tout d'abord nous avons appliqué cette méthodologie pour la synthèse diastéréosélective des Tfm-pipéridines. Les béta-aminocétals nécessaires à cette étude ont été facilement obtenus par l'addition conjuguée du phtalimide sur les énones correspondantes, suivi d'une céto-protection et d'une hydrazinolyse. Ces intermédiaires ont été soumis aux réactions de Mannich intramoléculaires avec divers aldéhydes, donnant ainsi un accès stéréosélectif aux analogues trifluorés de la pipéridine naturelle. Des réactions chimiques sur ces composés ont également permis la synthèse de nouveaux substrats tels que les 4-aza et 4-hydroxy Tfm-piperidines. Une version énantiosélective de cette stratégie alors a été réalisée avec succès au départ de béta-aminocétals énantiomériquement enrichi, préparés à partir d'une oxazolidine fluoré (FOX) par une réaction de type Mukaiyama-Mannich. L'emploi de ces nouvelles amines énantio-enrichies dans des conditions identiques de cyclisation avec différents aldéhydes a fourni une série de Tfm-pipéridines enantiopure. Cette stratégie a été validée par la première synthèse asymétrique des analogues trifluorométhylés des acides pipécoliques, des analogues l'acide gamma-aminobutyrique (GABA) et des structures polycycliques comme les indolizidines, contenant un groupe trifluorométhyleCLERMONT FD-BCIU Sci.et Tech. (630142101) / SudocSudocFranceF

Scope of Harmonisation of Pharmacopoeial Liquid Chromatography (LC) Methods for Diazepam and Its Related Substances

Drug analysis is an imperative activity to check the quality of a drug compound. Pharmacopoeial monographs provide important information about the quality of a drug substance. The expected quality of a medicine during period of use is also explained in such monographs. Analytical tools such as spectroscopic and chromatographic methods have been developed for such investigations. We have analysed the purity of a well known anxiolytic drug; diazepam, by using liquid chromatographic (LC) technique. It was noticed that with Zorbax Eclipse XDB – C8 (4.6 x 150 mm, 5 µm) column and recommended mobile phase comprising acetonitrile - methanol - potassium dihydrogen phosphate (22+34+44 v/v), the desired results obtained were not according the chromatograms provided by European Pharmacopeia (EP), but by using another column (ACE – 5 – C8) (4.6 x 150 mm, 5 µm), an extra peak of diazepam degradant was obtained, which showed that by using appropriate mobile phase containing CH3CN- CH3OH- KH2PO4 (20+32+48 v/v), the better results can be achieved. The mean retention time for diazepam analysis was 2.9 minutes

Scope of Harmonisation of Pharmacopoeial Liquid Chromatography (LC) Methods for Diazepam and Its Related Substances

Drug analysis is an imperative activity to check the quality of a drug compound. Pharmacopoeial monographs provide important information about the quality of a drug substance. The expected quality of a medicine during period of use is also explained in such monographs. Analytical tools such as spectroscopic and chromatographic methods have been developed for such investigations. We have analysed the purity of a well known anxiolytic drug; diazepam, by using liquid chromatographic (LC) technique. It was noticed that with Zorbax Eclipse XDB – C8 (4.6 x 150 mm, 5 μm) column and recommended mobile phase comprising acetonitrile - methanol - potassium dihydrogen phosphate (22+34+44 v/v), the desired results obtained were not according the chromatograms provided by European Pharmacopeia (EP), but by using another column (ACE – 5 – C8) (4.6 x 150 mm, 5 μm), an extra peak of diazepam degradant was obtained, which showed that by using appropriate mobile phase containing CH3CN- CH3OH- KH2PO4 (20+32+48 v/v), the better results can be achieved. The mean retention time for diazepam analysis was 2.9 minutes

Asymmetric synthesis of trifluoromethyl-piperidine based ?-aminoacids and of trifluoromethyl-indolizidines.

International audienceThe asymmetric synthesis of trifluoromethyl-piperidine-based g-aminoacids and of indolizidines bearing a trifluoromethyl group is reported. These rarely described compounds are prepared in a highly enantio-enriched form employing as key step an intramolecular Mannich type process, involving an enantiopure Tfm-aminoketal and ethyl oxobutenoate as aldehyde partner. Used strategy together with obtained compounds allows the access to a wide range of Tfm-N-(poly)heterocycles, structures of obvious interest for the research of new bioactive drugs

Physico-Chemical Characteristics of Pollinated and Non Pollinated Date Fruit of District Khairpur, Sindh, Pakistan

Elemental patterns are often used for the classification or identification of date fruit varieties. Five ripening stages of six date varieties were collected and studied from the pre ripening to the post ripening stage. Pollinated and non-pollinated date fruit of the same varieties were compared for their physical and chemical parameters. Physical parameters such as size, mass, colour, moisture, and pH were measured. In case of chemical characteristics the mineral composition of six different varieties of district Khairpur dates palm (Phoenix dactylifera L.) fruit (Gorho, Asul Khurmo, Nur Aseel, Ghuray Wari, Toto, and Allah Wari) were analysed using Atomic Absorption Spectroscopy (AAS). Generally, size, moisture and mineral content of the pollinated fruit increased up to 3rd and 4th stage then declined

Controlled synthesis of ammonium manganese tri-fluoride nanoparticles with enhanced electrochemical performance

Herein, ammonium manganese tri-fluoride (NH4MnF3) nanoparticles (similar to 20-80 nm) were synthesized via easy, non-sophisticated and environment friendly reverse micro-emulsion method for the first time. Two type i.e. sintered and non-sintered NH4MnF3 nanoparticles were prepared with different ratio by changing water to surfactant percentage while keeping the temperature constant at 22 degrees C. The structural, morphological and optical properties of as-prepared nanoparticles were investigated by x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), UV-vis spectroscopy and Fourier-Transform infrared (FTIR) spectroscopy. The electrochemical performances were measured by using cyclic voltammetry and the result shows that after sintering the performance are significantly improved up to similar to 0.079 mA g(-1). We hope, our approach will opens up a new opportunity for such materials in energy storage devices

Determination and Evaluation of Mineral Constituents of Medicinal Plants used for the Treatment of Asthma and other Ailments by Atomic Absorption Spectrophotometry

Mineral contents have been determined for thirty samples from three medicinal plants (Hibiscus rosa-sinensis, Salvadora oleoides and Euphoria hirta). Fifteen essential trace and toxic elements were determined, using atomic absorption spectrophotometer. Ten samples from each plant were collected from the vicinity of Jamshoro and Tandojam Agricultural University and drug stores. The edible parts of all three plants were digested with two known wet asking methods. It was observed that the levels of essential micronutrient Ca, Mg, Fe, Mn and Zn, in all there medicinal plants are found to be (3.491.3-3928.2), (2269.3-3617.3), (3.23-5.42), (6.13-7.33) and (4.22-6.94) mg/100g respectively on dried basis. The efficiency of digesting mineral acid mixtures was checked by certified reference sample of Spinach NBS-1570

Investigation of Essential Metals in Branch, Pericarp and Seed of three Date Varieties at Different Maturity Stages

Date fruit contains a wide range of metals, including essential and toxic elements. The aim of present study was to explore the amount of essential metals in branch, pericarp and seed of the date fruit in order to examine correlation of these metals at various maturity stages. The studied parts are generally considered as waste. Therefore, levels of essential elements such as Na, Mg, Ca, Fe, Mn and Zn were determined in the branch, pericarp and seed of three date varieties ( Dallay wari, Noori and Khaki wari) at four ripening stages (kimri, khalal, rutab and tamar) using atomic absorption spectrophotometry. Oven dried samples were digested separately in HNO3 and H2O2 following wet acid digestion method. Analytical results shows that Na, Mg, Fe, Zn, and Mn were not detected in branch, pericarp and seed in Dallay wari variety at tamar stage, while Na and Mn were also absent in branch of Noori at tamar stage, whereas Mn was present in pericarp and seed at tamar stage of Noori variety. However, Mg was not detected in branch and pericarp at rutab and tamar, while Fe was not detected in pericarp at rutab and tamar stage in Khaki wari vareity