Mecanismo de accion de los macrolidos citotoxicos amphinolidas X y J

Trabajo presentado en el XI Congreso de la Sociedad de Biofísica de España: "XXV años y más allá", celebrado en Murcia (España) , del 1 al 4 de junio de 201

Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-adrenal axis function in humans : a systematic review

BACKGROUND: Synthetic glucocorticoids are commonly used in reproductive medicine. Fetal organ systems are highly sensitive to changes in the intrauterine environment, including overexposure to glucocorticoids. Structural and functional alterations resulting from such changes may persist throughout life and have been associated with diverse diseases. One system that could be particularly sensitive to fetal glucocorticoid overexposure is the hypothalamic-pituitary-adrenal (hpa) axis. Many human studies have investigated this possibility, but a systematic review to identify consistent, emergent findings is lacking. METHODS: We systematically review 49 human studies, assessing the effects of intrauterine exposure to synthetic glucocorticoids on fetal, neonate, and infant hpa function. RESULTS: Study quality varied considerably, but the main findings held true after restricting the analyses to higher-quality studies: intrauterine exposure to synthetic glucocorticoids reduces offspring hpa activity under unstimulated conditions after pain but not pharmacological challenge. Although reduced unstimulated hpa function appears to recover within the first 2 wk postpartum, blunted hpa reactivity to pain is likely to persist throughout the first 4 months of life. There is some evidence that the magnitude of the effects is correlated with the total amount of glucocorticoids administered and varies with the time interval between glucocorticoid exposure and hpa assessment. CONCLUSIONS: This systematic review has allowed the demonstration of the way in which intrauterine exposure to various regimens of synthetic glucocorticoids affects various forms of hpa function. As such, it guides future studies in terms of which variables need to be focused on in order to further strengthen the understanding of such therapy, whilst continuing to profit from its clinical benefits

Synthèse de 1,2-aminoalcools par réarrangements sigmatropiques (synthèse totale de l amphidinolide j)

Les 1,2-aminoalcools sont fréquemment rencontrés dans des molécules naturelles ou d origine synthétique possédant des propriétés biologiques intéressantes. En outre, ces composés entrent dans la composition de nombreux auxiliaires ou catalyseurs chiraux. Une voie de synthèse efficace et stéréosélective de syn- et d anti-1,2 aminoalcools fonctionnalisés a été développée en utilisant des réarrangements [2,3] de Wittig d éthers 3-aza-allyliques comme étape-clé. Cette méthodologie a permis d accéder à des composés hétérocycliques oxygénés et azotés. Parallèlement à ces travaux, la synthèse totale de l amphidinolide J, un produit naturel cytotoxique d origine marine possédant une macrolactone à 15 chaînons a été réaliséePARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Chiral Phosphate in Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition: Ligand, Counterion, or Both?

International audienceInvestigations based on NMR spectroscopy, mass spectrometry, and DFT calculations shed light on the metallic species generated in the rhodium-catalyzed asymmetric [2+2+2] cycloaddition reaction between diynes and isocyanates with the chiral phosphate TRIP. The catalytic mixture comprising [{Rh(cod)Cl}2 ], 1,4-diphenylphosphinobutane (dppb), and Ag(S)-TRIP actually gives rise to two species, both having an effect on the stereoselectivity. One is a rhodium(I) complex in which TRIP is a weakly coordinating counterion, whereas the other is a bimetallic Rh/Ag complex in which TRIP is a strongly coordinating X-type ligand

Helical Bisphosphinites in Asymmetric Tsuji‐Trost Allylation: a Remarkable P:Pd Ratio Effect

International audienceThis article discloses a study on a chiral bis-phosphorylated-helical ligand in the palladium-catalyzed Tsuji-Trost allylation. The use of 2,15-bisphosphinite[6]helicenes allowed to evidence a remarkable ligand effect, in which the (R) and (S) isomeric products can be selectively formed as a direct function of the amount of ligand introduced. Study of the organometallic species involved through 31P NMR analysis of a model complex and X-Ray diffraction analysis together with DFT calculations shed light on this phenomenon

Gold-Catalyzed Polymerization Based on Carbene Polycyclopropanation

International audienceThe first polymerization exploiting the carbenic reactivity of homogeneous gold catalysis has been devised. In the presence of a gold catalyst, monomers incorporating both a propargylic ester and an alkene moiety polymerized through a metallocarbene generation/cyclopropanation sequence to afford the corresponding macromolecules. This approach constitutes an unprecedented example of cyclopropanation-based polymerization and allows access to original macro-molecule skeletons

Metalated-Arene-Phosphino Ligands: A Novel Approach to Open-Sided Gold Compounds

International audienc

Gold Compounds Anchored to a Metalated Arene Scaffold: Synthesis, X-ray Molecular Structures, and Cycloisomerization of Enyne

International audienceA novel series of pi-complexes of phosphino ligands, [Cp*Ru(eta(6)-arene-PAr2)][OTf], has been prepared in which the diarylphosphine unit is attached to a metalated pi-arene scaffold. These organometallic phosphino ligands display either an electron-donating methyl group (-PAr2 = -P(p-tol)(2)) or electron-withdrawing trifluoromethyl group (-PAr2 = -P(p-C6H4CF3)(2)). This unique class of metallo ligands was converted to heterodinuclear gold complexes upon treatment with [AuCl(tht)]. The molecular structures of [Cp*Ru(eta(6)-p-CH3C6H4-P(p-tol)(2)-Au-Cl)][OTf] and [Cp*Ru(eta(6)-C6H5-P(p-C6H4CF3)(2))-Au-Cl][OTf] were ascertained by single-crystal X-ray diffraction. A comparative study of these structures with that of [Cp*Ru(eta(6)-C6H5-PPh2-Au-Cl)][OTf] previously reported revealed important information about the electronic nature of the gold center when it is bonded to a -PPh2, -P(p-tol)(2), or -P(p-C6H4CF3)(2) metallo ligand. DFT computations also shed light on the effect of [Cp*Ru+] coordination to [AuCl(PAr3)] precatalysts. Several complexes of the family with electron-donating and -withdrawing groups were evaluated toward cycloisomerization reactions of a classical N-tethered 1,6-enyne. These results are presented and discussed

Gold-Catalyzed Polymerization Based on Carbene Polycyclopropanation

The first polymerization exploiting the carbenic reactivity of homogeneous gold catalysis has been devised. In the presence of a gold catalyst, monomers incorporating both a propargylic ester and an alkene moiety polymerized through a metallocarbene generation/cyclopropanation sequence to afford the corresponding macromolecules. This approach constitutes an unprecedented example of cyclopropanation-based polymerization and allows access to original macromolecule skeletons