151 research outputs found
Réaction de trifluorométhylthiolation électrophile et synthÚse de radioligands en imagerie médicale TEP pour la protéine α-synucléine
Part 1 : More and more applications for fluorinated molecules are being found in various fields, from materials to life sciences. In recent years, a growing interest has emerged in the association of the trifluoromethyl group with heteroatoms such as CF3O or CF3S. The CF3S moiety is of particular interest, because of its high hydrophobicity parameter (Ï=1.44). Consequently compounds bearing this group are important targets for various applications, in particular in medicinal chemistry and agrochemistry. However, the majority of previous methods described in the literature use toxic reagents under harsh conditions. Trifluoromethanesulfenamides (1st and 2nd generation) have demonstrated their potential in the electrophilic trifluoromethylthiolations. Because of their interesting reactivity, these two generations of shelf-stable reagents are now in the toolbox of organic chemists for the trifluoromethylthiolation of molecules, providing a convenient method to pursue less toxic pathways. Part 2 : α-synuclein aggregation is a neuropathological hallmark of many neurodegenerative diseases including Parkinsonâs disease (PD) and dementia with Lewy bodies (DLB), collectively termed synucleinopathies. PET imaging can reflect the amount and distribution of alpha-synuclein aggregates in the brain and would be advantageous to use for specific diagnosis of synucleinopathies in presymptomatic stages of disease. We focused our interest onto benzimidazole derivatives as small, planar and -delocalized compounds to design radiotracers of synuclein aggregates. Compounds based on the association of benzimidazole moiety, rigid linker (alkyne and triazole) and another aromatic part have been designed. The radiolabeling could be performed by nucleophilic substitution with K18F during the last step. With this convergent strategy, we could have acces to a large series of molecules to be evaluatedPartie 1 : De plus en plus de molĂ©cules fluorĂ©es sont utilisĂ©es dans bon nombre de domaines variĂ©s, allant des matĂ©riaux aux sciences de la vie. Ces derniĂšres annĂ©es, un intĂ©rĂȘt croissant a Ă©mergĂ© avec l'association du groupement CF3 avec un hĂ©tĂ©roatome, comme OCF3 ou SCF3. Le groupement SCF3 est trĂšs intĂ©ressant Ă cause de son paramĂštre d'hydrophobie (Ï=1.44). Par consĂ©quent, les composĂ©s portant ce groupement sont des cibles importantes pour de nombreuses applications, en particulier en chimie mĂ©dicinale. Cependant, la majoritĂ© des prĂ©cĂ©dentes mĂ©thodes dĂ©crites dans la littĂ©rature utilisent des rĂ©actifs toxiques dans des conditions drastiques. Les trifluoromĂ©thanesulfĂ©namides (1Ăšre et 2nde gĂ©nĂ©ration) ont dĂ©montrĂ© leur potentiel dans la trifluoromĂ©thylthiolation Ă©lectrophile. En raison de leur rĂ©activitĂ© intĂ©ressante, ces deux gĂ©nĂ©rations de rĂ©actifs stables sont maintenant dans la boĂźte Ă outils de la chimie organique pour la trifluoromĂ©thylthiolation de molĂ©cules. Partie 2 : Des aggrĂ©gats d'α-synuclĂ©ine sont une caractĂ©ristique neuropathologique de nombreuses maladies neurodĂ©gĂ©nĂ©ratives, notamment la maladie de Parkinson (MP) et la dĂ©mence Ă corps de Lewy (DLB), collectivement appelĂ©s synuclĂ©inopathies. L'imagerie TEP pourrait rĂ©vĂ©ler la quantitĂ© et la distribution des agrĂ©gats d'α-synuclĂ©ine dans le cerveau et serait plus avantageuse Ă utiliser pour le diagnostic spĂ©cifique de synuclĂ©inopathies prĂ©symptomatiques Ă diffĂ©rents stades de lamaladie. Nous avons concentrĂ© nos efforts sur des dĂ©rivĂ©s de benzimidazole comme composĂ©s de petites tailles, plans et Ï-dĂ©localisĂ©s pour concevoir des traceurs radioactifs des agrĂ©gats de la synuclĂ©ine. Ainsi des structures assemblant des benzimidazoles, un espaceur rigide (alcyne et triazole) et enfin une autre partie aromatique ont Ă©tĂ© envisagĂ©es. Le radiomarquage pourra ĂȘtre effectuĂ© par une substitution nuclĂ©ophile avec K18F au cours de la derniĂšre Ă©tape. Avec cette stratĂ©gie convergente, nous pourrions avoir accĂšs Ă une grande sĂ©rie de molĂ©cules Ă Ă©value
Divergent Access to (1,1) and (1,2)-Azidolactones from Alkenes using Hypervalent Iodine Reagents
A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol (on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones
Structural Reevaluation of the Electrophilic Hypervalent Iodine Reagent for Trifluoromethylthiolation Supported by the Crystalline Sponge Method for X-ray Analysis
Hypervalent iodine λ[superscript 3]-benziodoxoles are common electrophilic transfer reagents known for their enhanced stability compared to their non-cyclic analogues. Herein we present data showing that chlorobenziodoxole reacts with two different thiolate nucleophiles (thiocyanate and trifluoromethylthiolate), resulting in the formation of stable thioperoxy complexes rather than the expected benziodoxole derivatives. We further report a revised structure for the earlier described electrophilic trifluoromethylthiolation reagent (1), which was previously believed to contain the benziodoxole framework. Our findings, which are based on a combination of analytical techniques, including the recently introduced crystalline sponge method for X-ray analysis, unambiguously demonstrate that 1 is a thioperoxy compound both in solution and the solid state.National Institutes of Health (U.S.) (Award GM58160
Cyclic Hypervalent Iodine Reagents for Azidation: Safer Reagents and Photoredox-Catalyzed Ring Expansion
Azides are building blocks of increasing importance in synthetic chemistry, chemical biology, and materials science. Azidobenziodoxolone (ABX, Zhdankin reagent) is a valuable azide source, but its safety profile has not been thoroughly established. Herein, we report a safety study of ABX, which shows its hazardous nature. We introduce two derivatives, tBu-ABX and ABZ (azidobenziodazolone), with a better safety profile, and use them in established photoredox- and metal-mediated azidations, and in a new ring-expansion of silylated cyclobutanols to give azidated cyclopentanones
ChemInform Abstract: Acid-Catalyzed Synthesis of α-Trifluoromethylthiolated Carbonyl Compounds.
Electrophilic trifluoromethylthiolation reaction and synthesis of radioligand for medicinal imaging of lâα-synuclein
Partie 1 : De plus en plus de molĂ©cules fluorĂ©es sont utilisĂ©es dans bon nombre de domaines variĂ©s, allant des matĂ©riaux aux sciences de la vie. Ces derniĂšres annĂ©es, un intĂ©rĂȘt croissant a Ă©mergĂ© avec l'association du groupement CF3 avec un hĂ©tĂ©roatome, comme OCF3 ou SCF3. Le groupement SCF3 est trĂšs intĂ©ressant Ă cause de son paramĂštre d'hydrophobie (Ï=1.44). Par consĂ©quent, les composĂ©s portant ce groupement sont des cibles importantes pour de nombreuses applications, en particulier en chimie mĂ©dicinale. Cependant, la majoritĂ© des prĂ©cĂ©dentes mĂ©thodes dĂ©crites dans la littĂ©rature utilisent des rĂ©actifs toxiques dans des conditions drastiques. Les trifluoromĂ©thanesulfĂ©namides (1Ăšre et 2nde gĂ©nĂ©ration) ont dĂ©montrĂ© leur potentiel dans la trifluoromĂ©thylthiolation Ă©lectrophile. En raison de leur rĂ©activitĂ© intĂ©ressante, ces deux gĂ©nĂ©rations de rĂ©actifs stables sont maintenant dans la boĂźte Ă outils de la chimie organique pour la trifluoromĂ©thylthiolation de molĂ©cules. Partie 2 : Des aggrĂ©gats d'α-synuclĂ©ine sont une caractĂ©ristique neuropathologique de nombreuses maladies neurodĂ©gĂ©nĂ©ratives, notamment la maladie de Parkinson (MP) et la dĂ©mence Ă corps de Lewy (DLB), collectivement appelĂ©s synuclĂ©inopathies. L'imagerie TEP pourrait rĂ©vĂ©ler la quantitĂ© et la distribution des agrĂ©gats d'α-synuclĂ©ine dans le cerveau et serait plus avantageuse Ă utiliser pour le diagnostic spĂ©cifique de synuclĂ©inopathies prĂ©symptomatiques Ă diffĂ©rents stades de lamaladie. Nous avons concentrĂ© nos efforts sur des dĂ©rivĂ©s de benzimidazole comme composĂ©s de petites tailles, plans et Ï-dĂ©localisĂ©s pour concevoir des traceurs radioactifs des agrĂ©gats de la synuclĂ©ine. Ainsi des structures assemblant des benzimidazoles, un espaceur rigide (alcyne et triazole) et enfin une autre partie aromatique ont Ă©tĂ© envisagĂ©es. Le radiomarquage pourra ĂȘtre effectuĂ© par une substitution nuclĂ©ophile avec K18F au cours de la derniĂšre Ă©tape. Avec cette stratĂ©gie convergente, nous pourrions avoir accĂšs Ă une grande sĂ©rie de molĂ©cules Ă Ă©valuerPart 1 : More and more applications for fluorinated molecules are being found in various fields, from materials to life sciences. In recent years, a growing interest has emerged in the association of the trifluoromethyl group with heteroatoms such as CF3O or CF3S. The CF3S moiety is of particular interest, because of its high hydrophobicity parameter (Ï=1.44). Consequently compounds bearing this group are important targets for various applications, in particular in medicinal chemistry and agrochemistry. However, the majority of previous methods described in the literature use toxic reagents under harsh conditions. Trifluoromethanesulfenamides (1st and 2nd generation) have demonstrated their potential in the electrophilic trifluoromethylthiolations. Because of their interesting reactivity, these two generations of shelf-stable reagents are now in the toolbox of organic chemists for the trifluoromethylthiolation of molecules, providing a convenient method to pursue less toxic pathways. Part 2 : α-synuclein aggregation is a neuropathological hallmark of many neurodegenerative diseases including Parkinsonâs disease (PD) and dementia with Lewy bodies (DLB), collectively termed synucleinopathies. PET imaging can reflect the amount and distribution of alpha-synuclein aggregates in the brain and would be advantageous to use for specific diagnosis of synucleinopathies in presymptomatic stages of disease. We focused our interest onto benzimidazole derivatives as small, planar and -delocalized compounds to design radiotracers of synuclein aggregates. Compounds based on the association of benzimidazole moiety, rigid linker (alkyne and triazole) and another aromatic part have been designed. The radiolabeling could be performed by nucleophilic substitution with K18F during the last step. With this convergent strategy, we could have acces to a large series of molecules to be evaluate
J. Decottignies, Villiers le taciturne
Alazet Bernard. J. Decottignies, Villiers le taciturne. In: Romantisme, 1985, n°48. Dédales du sujet. pp. 126-127
Préface
Préface à l'ouvrage de Chloé Chouen "Marguerite Duras, une écriture de la prostitution", Garnier, 201
J. Decottignies, Villiers le taciturne
Alazet Bernard. J. Decottignies, Villiers le taciturne. In: Romantisme, 1985, n°48. Dédales du sujet. pp. 126-127
Ăclats de « la nuit sexuelle » chez Jean Genet
« Rien dans le jour ne se voit de la nuit ce passage » : la nuit pour Marguerite Duras est ce lieu sans forme oĂč advient ce qui se soustrait Ă la lumiĂšre pour mieux exister â lâamour, lâĂ©criture â et qui pourtant double de sa prĂ©sence Ă©vanouie, « engloutie » dirait Jean Genet, la lumiĂšre du jour sans pour autant y trouver sa place. « Obscure splendeur » qui ne peut se donner Ă lire quâen conjuguant des mots qui sâexcluent et se maintiennent ainsi, irrĂ©conciliables. De la « nuit enflammĂ©e » de..
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