Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Le dendroctone des pins du sud ou « Southern Pine Beetle » (Dendroctonus frontalis) est un coléoptère xylophage nuisible et ravageur des forêts d’Amérique du Nord qui a déjà causé plus de 900 millions de dollars de dégâts entre 1960 et 1990 et dont son surdéveloppement est de plus accéléré par le réchauffement climatique. Cet insecte vit en symbiose avec le champignon Entomocorticium sp. qui lui permet d’assimiler la lignine contenue dans le bois. Une particularité supplémentaire de ces dendroctones a été la découverte récente d’un deuxième symbiote d’origine bactérienne (Streptomyces sp. SPB74) qui a un rôle de protecteur chimique face aux antagonistes fongiques du dendroctone. La principale substance protectrice produite par ce symbiote est la mycangimycine, un acide gras polyènique contenant un cycle 1,2-dioxolane 3,5-disubstitué. Ce composé affecte peu le champignon vital du dendroctone mais a montré des activités antifongiques exceptionnelles, égales ou supérieures à l’amphotéricine B sur des champignons pathogènes de souche résistante ou non ainsi qu’une excellente activité anti-malarique sur Plasmodium falciparum.Dans ce manuscrit, nous avons rapporté quelques tentatives vers la synthèse de la mycangimycine, en particulier la formation du motif 1,2-dioxolane 3,5-disubstitué qui pourrait contribuer de manière prometteuse à de nombreuses activités biologiques comme antipaludique et antifongique, etc. Le premier travail a porté sur la synthèse du 1,2-dioxolane en utilisant des cyclopropanols comme intermédiaires, par un processus d'ouverture de cycle par oxydation. À la suite de cela, certains analogues saturés de la mycangimycine ont été préparés avec un rendement relativement élevé. Dans la deuxième partie de ce manuscrit, nous avons développé une méthodologie de synthèse sur l'addition nucléophile sur des peroxyketal cycliques via la formation d’un ion peroxycarbenium par l’action d’un acide Lewis. Différents analogues synthétiques et intermédiaires de synthèse ont été évalués in vitro dans les domaines antiparasitaires. / The southern pine beetle (Dendroctonus frontalis) ecosystem has been strongly studied because of the economic losses of conifer production in North America. From these researches, it has emerged that this pine beetle possesses a very complex natural associations with trees, fungi, mites. Recently some reports indicated that a bacterian symbiont (Streptomyces sp. SPB74) produces an unprecedent polyene peroxide, named mycangimycin, which plays a role of antifungal and antiparasitic. This molecule is a polyenic fatty acid containing a 3,5-disubstituted 1,2-dioxolane ring which exhibits exceptional antifungal activity against a wide variety of fungi and activities as antimalarial agent against Plasmodium falciparum.In this manuscript, we reported some attempts towards the synthesis of mycangimycin, especially for the formation of 3,5-disubstituted-1,2-dioxolane moiety which could contribute promisingly to many biological activities as antimalarial and antifungal. The first work focused on the synthesis of the 3,5-disubsituted-1,2-dioxolane ring using cyclopropanols as intermediates, through an oxidative ring opening process. As a result of that, some saturated analogues of mycangimycin were prepared in relatively high yield. In the second part of this manuscript, we have developed an available methodology of nucleophile addition to the peroxycarbenium ions derived from Lewis acid-mediated ionization of 3-alkoxy-1,2-dioxolanes providing 3,5-disubstituted-1,2-dioxolane compounds. Various synthetic analogues or intermediates have been evaluated in in vitro in antiparasitic domains.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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No description available.

The dissociative photoionization reactions of two small, oxygenated organics, namely 1,3-dioxolane and methyl vinyl ketone, were studied by photoelectron photoion coincidence (PEPICO) spectroscopy. Experiments involving 1,3-dioxolane were carried out in the photon energy range of 9.5‒13.5 eV. The statistical thermodynamics model shows that a total of six dissociation channels are involved in the formation of three fragment ions, namely C3H5O2+ (m/z 73), C2H5O+ (m/z 45) and C2H4O+ (m/z 44), with two channels contributing to the formation of each. By comparing the results of ab initio quantum chemical calculations to the experimentally derived appearance energies of the fragment ions, the most likely mechanisms for these unimolecular dissociation reactions are proposed, including a description of the relevant parts of the potential energy surface.In the case of methyl vinyl ketone, an important atmospheric intermediate in the oxidation of isoprene, between 9.5‒13.8 eV four main fragment ions were detected at m/z 55, 43, 42, and 27 aside from the parent ion at m/z 70. The m/z 55 fragment ion (C2H3CO+) is formed from ionized MVK by direct methyl loss, while breaking the C–C bond on the other side of the carbonyl group results in the acetyl cation (CH3CO+, m/z 43) and the vinyl radical. The m/z 42 fragment ion is formed via a CO loss from the molecular ion after a methyl shift. The lightest fragment ion, the vinyl cation (C2H3+ at m/z 27), is produced in two different reactions: acetyl radical loss from the molecular ion and CO-loss from C2H3CO+. Their contributions to the m/z 27 signal are quantified based on the acetyl and vinyl fragment thermochemical anchors and quantum-chemical calculations. Based on the experimentally derived appearance energy of the m/z 43 fragment ion, a new, experimentally derived heat of formation is proposed for gaseous methyl vinyl ketone (ΔfH0K = −94.2 ± 4.8 kJ mol−1; ΔfH298K = −110.4 ± 4.8 kJ mol−1), together with cationic heats of formation and bond dissociation energies.