Pyrrolo[1,2-a]pyrazine is one of the isomers of pyrolodiazine family. Pyrrolo[1,2-a]pyrazine possesses a bicyclic heteroaromatic structure that have 10 electrons. It has various biological importances in synthetic chemistry / therefore, many different approaches to generate this skeleton have been developed so far. In this study, our prior aim was to develop a new synthetic methodology for the formation of pyrrolo[1,2-a]pyrazine moiety. In the first part of this focus, the starting compound, methyl 2-(2-methoxy-2-oxoethyl)-1-(prop-2-yn-1-yl)-1H-pyrrole-3-carboxylate was successfully synthesized, then the conversion of the ester group at the lower arm to the amine group was carried out. Heteroatom cyclization catalyzed by CuI afforded the desired substituted pyrrolo[1,2-a]pyrazine structure. In the second part, it was aimed to synthesize new compounds with unusual structures which are not described in the literature / namely, as pyrrolo[1,2-a]pyrazine N-oxide. In this direction, first pyrrole was submitted to Vilsmeier-Haack reaction to attach a formyl group at C-2. Substitution reaction then effectively gave 1-(prop-2-yn-1-yl)-1H-pyrrole-2-carbaldehyde, which was a key molecule to synthesize the aldoxime. AuCl3 catalyzed cyclization of the corresponding oxime afforded pyrrolo[1,2-a]pyrazine N-oxide. In the next step, Sonogashira coupling reactions were carried out to obtain terminal alkynes (RC&equiv / CR&#039 / ) starting from 1-(prop-2-yn-1-yl)-1H-pyrrole-2-carbaldehyde. The aim of this part was to study the effect of aryl groups to the activated alkyl functional group by a metal catalyst. In this case, unexpected oxime-oxime transformation was observed, which is unprecedented in the literature

Cette thèse est consacrée à la synthèse et à la caractérisation physique de nouveaux polymères de coordination bidimensionnels (2D) possédant un ordre magnétique et/ou une conductivité électrique à haute température. La présence simultanée de ces deux propriétés au sein d'un même matériau représente un formidable défi pour la synthèse de matériaux multifonctionnels utilisables dans le traitement et le stockage des données de nouvelles générations. Notre approche pour synthétiser de tels systèmes implique l'utilisation du ligand pontant organique redox-actif pyrazine, et de métaux de transition réducteurs. Le chapitre I présente quelques aspects généraux sur la chimie redox, la délocalisation des charges et la valence mixte qui sont essentiels à la compréhension des résultats expérimentaux. Les différentes approches de synthèse de polymères de coordination conducteurs et magnétiques sont également décrites. Le chapitre II donne un aperçu général des concepts fondamentaux concernant la conductivité électrique, le magnétisme et la spectroscopie d'absorption des rayons X. Le chapitre III analyse la synthèse et la caractérisation physique du composé CrCl2(pyrazine)2 présentant à la fois un ordre magnétique et une conductivité électrique. Les chapitres IV et V sont consacrés à l'étude de nouveaux composés MX2(pyrazine)2 en faisant varier M (Ti, V) et X (OSO2CH3, Br et I). L’objectif est de déterminer l’effet de la nature du centre métallique et du ligand axial sur les propriétés magnétiques et électriques. Enfin, le chapitre VI illustre comment la chimie redox post-synthétique peut entraîner une augmentation impressionnante de la température de l'ordre magnétique dans les matériaux 2D à base de pyrazine. / This thesis is devoted to the synthesis and physical characterization of new two-dimensional (2D) coordination polymers that present high-temperature magnetic order and/or electrical conductivity. The simultaneous implementation of these two properties within a single material represents a formidable challenge in the synthesis of multifunctional materials for next-generation data processing and storage. Our approach to synthesize such systems involves the use of the redox-active organic bridging ligand, pyrazine, and reducing transition metals. Chapter I presents some general aspects of redox-activity, charge delocalization and mixed-valency that are crucial for the understanding of the experimental results. The different approaches for the synthesis of conducting and magnetic coordination polymers are also described. Chapter II provides a general view on the fundamental concepts regarding electrical conductivity, magnetism and X-ray absorption spectroscopy. Chapter III deals with the synthesis and extensive physical characterization of the coordination solid CrCl2(pyrazine)2, which exhibits both magnetic order and electrical conductivity. Chapters IV and V are devoted to the study of the effect of the anionic co-ligands and metal centers, respectively, in the family of MX2(pyrazine)2 (M = Cr, Ti, V and X = OSO2CH3, Br and I) coordination solids. Finally, Chapter VI illustrates how post-synthetic redox chemistry can result in an impressive enhancement of the magnetic order temperature in 2D layered pyrazine-based materials.

Les complexes de platine ont été abondamment étudiés depuis la description de l'effet trans par le chercheur russe Chernayev. Cependant, les complexes de platine contenant la pyrazine ou la pyrimidine non substituées sont rares. De nouveaux types de complexes cis et trans de platine(II) contenant des ligands mixtes, Pt(Ypy)(pz/pm)CI₂, (où Ypy =dérivé de la pyridine, pz=pyrazine et pm=pyrimidine) ont été synthétisés par la réaction de K[Pt(Ypy)Cl₃] avec (pz/pm) en milieu aqueux dans des proportions 1:1. La même synthèse dans des proportions 2:1 a conduit à des dimères où le ligand pyrazine/pyrimidine forme un pont mettant en jeu ses deux atomes d'azote dans des liaisons de coordination. Seuls les isomères trans,trans-CI₂(Ypy)Pt(µ-pz/pm)Pt(Ypy)Cl₂ ont pu être isolés. Tous les complexes ont été caractérisés par spectroscopies IR et de résonance magnétique multinucléaire (¹⁹⁵Pt, ¹H et ¹³C). La spectroscopie infrarouge (v(Pt-Cl)) ainsi que ks constantes de couplage J(¹⁹⁵Pt-¹H) et J(¹⁹⁵Pt-¹³C) donnent des informations sur la géométrie des complexes. En effet, un signal unique est observé dans la région des élongations v(Pt-CI) pour les complexes trans et deux pour ceux de configuration cis. D'autre part, les constantes de couplage ³J(¹⁹⁵Pt-¹H) sont un peu plus grandes pour les complexes de géométries cis que pour ceux de configuration trans. Les valeurs des déplacements chimiques en RMN du ¹⁹⁵Pt donnent des informations sur la densité électronique autour du platine, celles en RMN ¹H et ¹³C sur celles des ligands. L'influence de la position des groupements méthyle sur le noyau pyridine a été étudiée grâce à ces méthodes spectroscopiques. Les complexes comportant des dérivés de la pyridine substitués en 2 et en 6 montrent des résonances à plus faibles champs en RMN ¹⁹⁵Pt ce qui a été attribué à l'effet de solvant. Les signaux en RMN ¹⁹⁵Pt des monomères cis ont été observés à des champs plus élevés que ceux des analogues trans. Les dimères trans ont été observés à des champs semblables (complexes de la pyrimidine) ou un peu plus faibles (complexes de la pyrazine) que les monomères trans. Ces résultats ne plaident pas en faveur d'une rétrodonation importante Pt→N. Toutefois, les résultats en spectroscopie RMN ¹⁹⁵Pt résultent d'un ensemble de plusieurs effets électroniques, qui sont difficiles à séparer. Si donc une rétrodonation existe, elle serait faible comparativement à celle observée avec des ligands sulfoxyde ou phosphine. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Platine, Pyridine, Pyrazine, Pyrimidine, RMN, Infrarouge, Effet de solvant.

According to the theory of Traditional Chinese Medicine, the main etiology of stroke results from blood stasis. Ligustic Rhizoma (LR), a Chinese herb, is considered to stimulate stasis-dispelling. As Tetramethyl Pyrazine (TMP) is a major component of LR, the aim of the present study is to investigate the effects of TMP on cerebral infarct. We establish an animal model of cerebral infarct by occluding the both common carotid arteries and right middle cerebral artery for 90 minutes, then reperfusing for 24 hrs. Effects of TMP on cerebral infarct are evaluated by the ratio of infarction areas and modified neurologica severity scale (mNSS). In addition, we observe the changes of ED1, tumor necrosis factor-£\ (TNF-£\) and interleukin-1£] (IL-1£]) immuno-reacting cells in the infarction region. The founding indicate that pre-treatment with TMP 100 mg/kg, 120 mg/kg and 140 mg/kg, and post-treatment with TMP 100 mg/kg will decrease the ratio of cerebral infarction area and the neurological deficit. Moreover, pre-treatment TMP 100 mg/kg also decreases ED1, TNF-£\ and IL-1£] immuno-reacting cell. In conclusion, TMP can decrease cerebral infarction area and neurological deficit. The effects of TMP, at least in part, are closely related to microglia, TNF-£\ and IL-1£], suggesting that TMP can be used to treat stroke in human.

The main purpose of the theses was to find if the abiotic elicitor 2,4,6-trimethyl-N-(pyrazine- 2-yl)benzenesulfonamide has any influence on the secondary metabolites production in callus and suspension cultures of Hypericum perforatum L. The cultivation was taking place in the Murashige a Skoog (MS) nutrient medium enriched by the growth regulator - alpha-naphthyl acetic acid at the concentration of 1 mg.L-1 . The elicitor was added to the cultures at the three levels of concentration: c1= 100.0 mg/100 ml; c2= 10.0 mg/100 ml; c3= 1.00 mg/100 ml. The individual samples were taken after 6, 24, 48, 72 and 168 hours of the elicitor application. The control samples without the elicitor were taken after 6, 48 and 168 hours. The collected samples were dried and subsequently transformed into methanol extracts in order to determine secondary metabolites content (rutin, hyperoside and quercetin) by HPLC method. Release of these metabolites into nutrient media was also subject of this observation. The elicitation has influenced production of the secondary metabolites, particularly in callus cultures, wherein several statistically significant values, characterizing increase in their production, were measured. The highest content of rutin (0.169 mg.g-1 DW) was determined in callus culture after 168 hours when...

1 Abstract Elicitation method is one way to increase the production of secondary metabolites in in vitro of plant cultures and this work deals with this problem. Its aim was to find the positive effect of 2-hydroxy-4-(imidazo[1,2-a]pyrazine-2-carboxamide)benzoic acid from the group of pyrazine derivates on the production of isoflavonoids in in vitro cultures of Genista tinctoria L. Isoflavonoids play an important role in therapy of climacteric problems or they are promising substances of therapy various cancer types due to their affinity to estrogens β-receptors. This plant or rather its in vitro cultures are a potencial sources of isoflavonoids. Suspension and callus cultures of Genista tinctoria L. were used for elicitation. They were cultivated on Schenk & Hildebrant medium with the addition of 2,4-dichlorophenoxyacetic acid (2,4-D) as growth regulator at a concentration of 1 ml/l. The elicitor solution was added to the cultures at three concentrations: 3.3642 × 10-3 mol/l; 3.3642 × 10-4 mol/l; 3.3642 × 10-5 mol/l. The samples were taken at intervals of 6, 24, 48, 72 and 168 hours and then they were analyzed by HPLC method. At the same time intervals the samples of medium, where isoflavonoids were released, were analyzed. The biggest production of isoflavonoid was reached in suspension culture. The...

Les complexes de lanthanides, grâce à un temps de décroissance de luminescence élevé, sont parmi les sondes les plus sensibles puisqu'ils permettent une mesure de luminescence en temps résolu. Ces complexes sont à la base de certaines technologies permettant, in vitro et/ou in cellulo, la détection d'interactions entre biomolécules et/ou leur quantification et localisation. Elaborer des complexes de lanthanides présentant un maximum d'absorption au-delà de 350 nm reste un des défis majeurs alors qu'à ces rayonnements UV le matériel biologique se dégrade moins. Un chélate luminescent d'Eu(III) fondé sur une structure original bis-pyridinylpyrazine possédant un maximum d'absorption à 345 nm, stable jusqu'à 355 nm, a été synthétisé. Un analogue portant une fonction bioconjugable a permis, après activation par un réactif de couplage homo-bifonctionnel, de marquer des anticorps anti c-myc et anti HA. La deuxième partie du projet porte sur le développement de sondes lanthanidiques photoréactives capables de détecter spécifiquement, puis de s'accrocher de façon covalente à des protéines d'intérêt taguées (polyHis ou polyAsp), afin de suivre leur trafic cellulaire et leurs interactions avec d'autres biomolécules. Idéalement, l'étape de reconnaissance devrait avoir lieu entre l'étiquette et le cation métallique suivi par l'accrochage covalent initié par photoactivation. Ceci devrait conduire à une modulation du signal émis par le marqueur lanthanidique. Pour ce faire, différents complexes comportant des benzophénones, azido-coumarines ou quinolinones ont été synthétisés.

This thesis describes the development of new synthetic methodologies for preparation of bioactive interesting compounds, e.g. substituted pyridines, piperidines or piparazines. Thesecompounds are synthesized from commercially available, cheap and easily prepared reagents, videlicet the reaction between Grignard reagents and heterocyclic N-oxides.  The first part of this thesis deals with an improvement for synthesis of dienal-oximes and substituted pyridines. This was accomplished by a rapid addition of Grignard reagents to pyridine N-oxides at rt. yielding a diverse set of substituted dienal-oximes. During these studies, it was observed that the obtained dienal-oxmies are prone to ring-close upon heating. By taking advantage of this, a practical synthesis of substituted pyridines was developed. In the second part, an ortho-metalation of pyridine N-oxides using Grignard reagents is discussed. The method can be used for incorporation of a range of different electrophiles, including aldehydes, ketones and halogens. Furthermore, the importance for incorporation of halogens are exemplified through a Suzuki–Miyaura coupling reaction of 2-iodo pyridine N-oxides and different boronic acids. Later it was discovered that if the reaction temperature is kept below -20 °C, the undesired ringopening can be avoided. Thus, the synthesis of 2,3-dihydropyridine N-oxide, by reacting Grignard reagents with pyridine N-oxides at -40 °C followed by sequential addition of aldehyde or ketone, was accomplished. The reaction provides complete regio- and stereoselectivity yielding trans-2,3-dihydropyridine N-oxides in good yields. These intermediate products could then be used for synthesis of either substituted piperidines, by reduction, or reacted in a Diels–Alder cycloaddtion to give the aza-bicyclo compound. In the last part of this thesis, the discovered reactivity for pyridine N-oxides, is applied on pyrazine N-oxides in effort to synthesize substituted piperazines. These substances are obtained by the reaction of Grignard reagents and pyrazine N-oxides at -78 °C followed by reduction and protection, using a one-pot procedure. The product, a protected piperazine, that easily can be orthogonally deprotected, allowing synthetic modifications at either nitrogens in a fast and step efficient manner. Finally, an enantioselective procedure using a combination of PhMgCl and (-)-sparteine is discussed, giving opportunity for a stereoselective synthesis of substituted piperazines.

This work presents a new implementation of the QP algorithm, a computer method to diagonalize the extremely large matrices arising in multimode vibronic problems. Benchmark calculations are included, showing the accuracy of the program. The QP algorithm is extended to treat multiple electronic surfaces for competitive control and this is demonstrated with an Hamiltonian including three electronic states, a model of the benzene radical cation. Finally, the evolution of zeroth-order states in a simple two electronic states, two dimensional model with a conical intersection is explored, towards building a time-dependent view of overlapping resonances coherent control.

This work presents a new implementation of the QP algorithm, a computer method to diagonalize the extremely large matrices arising in multimode vibronic problems. Benchmark calculations are included, showing the accuracy of the program. The QP algorithm is extended to treat multiple electronic surfaces for competitive control and this is demonstrated with an Hamiltonian including three electronic states, a model of the benzene radical cation. Finally, the evolution of zeroth-order states in a simple two electronic states, two dimensional model with a conical intersection is explored, towards building a time-dependent view of overlapping resonances coherent control.