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

Nott Katherine (2007). Synthèse de dérivés tensioactifs de virginiamycine et étude de leurs propriétés (Thèse de doctorat). Gembloux, Académie universitaire Wallonie-Europe, Faculté Universitaire des Sciences Agronomiques, 317 p., 66 tabl., 79 fig. Résumé : Suite à la purification du facteur M1 de la virginiamycine, des dérivés ont été synthétisés et purifiés. Deux types de mono-dérivés ont été obtenus : des esters avec des acides gras (modification de M1 au niveau de lhydroxyle en C-14) et des oximes (liaison chimiosélective) dérivées dacides aminés (réaction avec le carbonyle cétonique en C-16). Des di-dérivés ont également été produits en modifiant simultanément ces deux sites réactionnels avec un acide gras dune part et un aminooxy acétyle acide aminé dautre part. Lidentité des dérivés a été confirmée par un ensemble de techniques spectrales (infrarouge, masse et résonance magnétique nucléaire). Leurs propriétés tensioactives fondamentales ont été étudiées et un criblage de leurs activités antimicrobiennes a été réalisé. Laugmentation simultanée des caractères hydrophobe et hydrophile de M1 (cas des di-dérivés) est nécessaire pour lui conférer un caractère tensioactif marqué. Les di-dérivés présentent des caractéristiques tensioactives (cinétique dadsorption et formation de micelles) similaires voire supérieures à celles dautres tensioactifs classiques de la littérature et de certains biosurfactants tels que les lipopeptides de Bacillus subtilis. La synthèse de di-dérivés a augmenté la capacité de M1 à pénétrer dans un modèle membranaire. Le rôle favorable de M1 sur certaines propriétés de surface a été mis en évidence par comparaison des propriétés des di-dérivés avec celles de molécules témoins de type amide formées entre un acide gras et un acide aminé. La gamme de di-dérivés synthétisés a permis de contribuer aux études des relations structure fonction dans le domaine des tensioactifs. Le criblage des activités antibactériennes des dérivés a montré limportance des fonctions hydroxyle et cétone pour lactivité antibiotique initiale de M1. Les di-dérivés ainsi que les molécules témoins synthétisées présentent une activité vis-à-vis de certaines bactéries et moisissures. Cela pourrait être attribué à la capacité de ces molécules à déstabiliser les membranes de ces microorganismes. Nott Katherine (2007). Synthesis of surface active derivatives of virginiamycin and study of their properties (PhD thesis in french). Gembloux, Belgium, University Academy Walloon Region-Europe, Gembloux Agricultural University, 317 p., 66 tabl., 79 fig. Summary : Following the purification of the M1 factor of virginiamycin, derivatives have been synthesised and purified. Two types of mono-derivatives have been obtained : esters with fatty acids (modification of M1 at its C-14 hydroxyl) and oximes (chemoselective ligation) with aminooxylated amino acids (reaction with the ketone carbonyl at C-16). Bis-derivatives have also been produced by simultaneously modifying the two reactive sites with a fatty acid on one side and an aminooxylated amino acid on the other. The identity of each derivative has been confirmed by a combination of spectral techniques (infrared, mass and nuclear magnetic resonance). Their fundamental tensioactive properties have been studied and screening of their activity against microorganisms has been undertaken. The simultaneous increase of M1s hydrophobic and hydrophilic character (the case of the bis-derivatives) was necessary to render M1 surface active. The bis-derivatives have surface active characteristics (adsorption kinetics and micelle formation) similar or even superior to those of classical surfactants of the literature and of some biosurfactants such as Bacillus subtiliss lipopeptides. The synthesis of the bis-derivatives has enhanced M1s capacity to penetrate a biological membrane model. M1s positive impact on some surface properties has been shown by comparison with amide type molecules obtained by reacting a fatty acid with an amino acid. The range of the synthesised bis-derivatives has allowed this work to contribute to the studies of the relationships between surfactants structures and their properties. The screening of the derivatives antibacterial activities has shown the importance of the hydroxyl and ketone groups for M1s initial antibiotic activity. The bis-derivatives and the reference molecules show an activity against some bacteria and fungi. This may be due to their capacity to destabilise the microorganisms membranes.