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Étude de nouvelles méthodologies d'arylation directe en séries azole et pyridine (Application à la synthèse de coeurs de thiopeptides antibiotiques de la série d)

Face à l apparition grandissante de souches bactériennes multi-résistantes à l arsenal d antibiotiques actuels, les thiopeptides antibiotiques, bien que connus depuis plus de 60 ans, suscitent actuellement un fort regain d intérêt. En effet, cette classe de molécules présente une forte activité antibiotique contre des souches bactériennes résistantes et multirésistantes, et met en œuvre deux modes d inhibition originaux de la synthèse protéique encore inexploités en thérapie antibiotique humaine. Leur développement pharmacologique est en particulier freiné par la difficulté de préparation de ces molécules très complexes. L'élaboration d'une stratégie innovante de synthèse de la partie la plus complexe de ces molécules, le cœur hétérocyclique est étudiée dans ce travail. Cette approche repose sur l'étude et la valorisation de nouvelles méthodologies de fonctionnalisation directe des liaisons C-H et C-X de mono- et bis-thiazoles avec une large gamme d hétéroaromatiques. Sa viabilité est démontrée par la préparation du cœur hétérocyclique commun aux amythiamicines.Due to the emergence of multiresistant bacterial strains to standard antibacterial treatments, thiopeptides antibiotics are actually highly considered, though they are known for 60 years. They show an excellent antibiotic activity against multiresistant bacterial strains, and implement two originals inhibition mechanisms of protein synthesis, still unemployed in human therapy. However, the difficulty to prepare these complex macromolecules limits their pharmacological development. The development of a new strategy to synthetize the most complicated part of these macromolecules, their heterocyclic core, is studied here in. This approach is based on the study and the exploitation of novel direct C-H and C-X transition-metal-catalyzed couplings of mono- and bithiazoles units with a broad panel of heteroaromatics. Its viability is here demonstrated trough the multi-step synthesis of the common heterocyclic core of amythiamicins.ROUEN-INSA Madrillet (765752301) / SudocSudocFranceF

Elementos de medicina del doctor Juan Brown

Encabezamiento completado con Catalogo de la Real Academia de Medicina de Barcelona, p. 294.Datos de editor tomados de colofón.Sign. : [*]4, 2*2, A-F4, G1-2, [calderón]4, G3-4, H-M4, N3, N2-N54s, N65s, O-Z4, 2A-2O4, 2P2.Error de pag., de p. XLVI pasa a XLIX

Elementos de medicina del doctor Juan Brown

Sign. : A-Z4, 2A-2P4, 2Q1.Error de pag., de p. 128 pasa a 139

Phytotoxins Produced by Fungi Associated with Grapevine Trunk Diseases

Up to 60 species of fungi in the Botryosphaeriaceae family, genera Cadophora, Cryptovalsa, Cylindrocarpon, Diatrype, Diatrypella, Eutypa, Eutypella, Fomitiporella, Fomitiporia, Inocutis, Phaeoacremonium and Phaeomoniella have been isolated from decline-affected grapevines all around the World. The main grapevine trunk diseases of mature vines are Eutypa dieback, the esca complex and cankers caused by the Botryospheriaceae, while in young vines the main diseases are Petri and black foot diseases. To understand the mechanism of these decline-associated diseases and the symptoms associated with them, the toxins produced by the pathogens involved in these diseases were isolated and characterised chemically and biologically. So far the toxins of only a small number of these decline fungi have been studied. This paper presents an overview of the toxins produced by the most serious of these vine wood pathogens: Eutypa lata, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and some taxa in the Botryosphaeriaceae family, and examines how these toxins produce decline symptoms. The chemical structure of these metabolites and in some cases their vivotoxin nature are also discussed