Oxydes de phosphines secondaires P-chirogéniques : nouvelle synthèse stéréosélective et applications

A new stereoselective synthesis of phosphinous acid boranes is described by hydrolysis of aminophosphines boranes prepared by reaction of the oxazaphospholidine complex derived from ephedrine with organolithium reagents.By reaction with a strong acid, the phosphinous acid boranes lead to the corresponding P-chirogenic secondary phosphine oxides in very good yields (90%) and with complete retention of the configuration at the phosphorus atom. The secondary phosphine oxides have been used in asymmetric hydrogenation and intramolecular Heck cyclisation using rhodium and palladium complexes, respectively. In a second part, a new synthesis of P-chirogenic ortho-halogenophenyl phosphine oxides is described. The principle of this synthesis is based on the addition of secondary phosphine oxides to a benzyne, prepared in situ from dihalogenobenzene. The o-halogenophenylphosphine oxides were used to prepare many functionalized derivatives in ortho position by reactions such as homocoupling with copper or heterocoupling catalyzed by palladium complexes. In the last part, the synthesis of chiral copper clusters was performed using P-chirogenic monophosphines. The X-ray structure, circular dichroism, and the photophysical properties of the chiral clusters were presented.Une nouvelle synthèse stéréosélective d’acides phosphineux-borane est décrite par hydrolyse d’aminophosphines borane préparées par réaction d'organolithiens sur un complexe d'oxazaphospholidine-borane dérivé de l'éphédrine. Par réaction avec un acide fort, ces acides phosphineux-borane conduisent aux oxydes de phosphines secondaires P-chirogéniques correspondants avec de très bons rendements (90%) et rétention complète de la configuration sur l'atome de phosphore. Les oxydes de phosphines secondaires ont été utilisés en catalyses d'hydrogénation et de Heck asymétriques par des complexes de rhodium et de palladium. Dans une seconde partie, une nouvelle synthèse d’oxydes de phosphines P-chirogéniques substitués par des groupements ortho halogénophényles a été décrite. Le principe de cette synthèse repose sur l’addition d’un oxyde de phosphine secondaire sur un benzyne préparé in situ à partir de dihalogénobenzène. Ces oxydes de phosphines o-halogénés ont été utilisés en synthèse de nouveaux dérivés fonctionnalisés en position ortho par des réactions d’homocouplage par le cuivre ou d’hétérocouplage catalysée par des complexes de palladium. Dans une dernière partie, la préparation de clusters de cuivre chiraux a été réalisée en utilisant des monophosphines P-chirogéniques. La structure par rayons X, le dichroïsme circulaire, et les propriétés photophysiques des clusters chiraux sont présentés

P-chirogenic secondary phosphine oxides : new synthesis and applications

Une nouvelle synthèse stéréosélective d’acides phosphineux-borane est décrite par hydrolyse d’aminophosphines borane préparées par réaction d'organolithiens sur un complexe d'oxazaphospholidine-borane dérivé de l'éphédrine. Par réaction avec un acide fort, ces acides phosphineux-borane conduisent aux oxydes de phosphines secondaires P-chirogéniques correspondants avec de très bons rendements (90%) et rétention complète de la configuration sur l'atome de phosphore. Les oxydes de phosphines secondaires ont été utilisés en catalyses d'hydrogénation et de Heck asymétriques par des complexes de rhodium et de palladium. Dans une seconde partie, une nouvelle synthèse d’oxydes de phosphines P-chirogéniques substitués par des groupements ortho halogénophényles a été décrite. Le principe de cette synthèse repose sur l’addition d’un oxyde de phosphine secondaire sur un benzyne préparé in situ à partir de dihalogénobenzène. Ces oxydes de phosphines o-halogénés ont été utilisés en synthèse de nouveaux dérivés fonctionnalisés en position ortho par des réactions d’homocouplage par le cuivre ou d’hétérocouplage catalysée par des complexes de palladium. Dans une dernière partie, la préparation de clusters de cuivre chiraux a été réalisée en utilisant des monophosphines P-chirogéniques. La structure par rayons X, le dichroïsme circulaire, et les propriétés photophysiques des clusters chiraux sont présentés.A new stereoselective synthesis of phosphinous acid boranes is described by hydrolysis of aminophosphines boranes prepared by reaction of the oxazaphospholidine complex derived from ephedrine with organolithium reagents.By reaction with a strong acid, the phosphinous acid boranes lead to the corresponding P-chirogenic secondary phosphine oxides in very good yields (90%) and with complete retention of the configuration at the phosphorus atom. The secondary phosphine oxides have been used in asymmetric hydrogenation and intramolecular Heck cyclisation using rhodium and palladium complexes, respectively. In a second part, a new synthesis of P-chirogenic ortho-halogenophenyl phosphine oxides is described. The principle of this synthesis is based on the addition of secondary phosphine oxides to a benzyne, prepared in situ from dihalogenobenzene. The o-halogenophenylphosphine oxides were used to prepare many functionalized derivatives in ortho position by reactions such as homocoupling with copper or heterocoupling catalyzed by palladium complexes. In the last part, the synthesis of chiral copper clusters was performed using P-chirogenic monophosphines. The X-ray structure, circular dichroism, and the photophysical properties of the chiral clusters were presented

Applications and stereoselective syntheses of P-chirogenic phosphorus compounds

International audiencePhosphorus compounds bearing chirality on the P-center are usually qualified as P-chirogenic or P-stereogenic. This chemical class concerns natural products, agrochemistry, molecular materials, biology and pharmacy, although it is certainly in coordination chemistry and in asymmetric catalysis using chiral transition metal complexes that P-chirogenic phosphorus compounds are the most used. The chiral phosphine ligands and their uses in asymmetric metal-catalyzed reactions have been widely reviewed in literature. However, an overview covering the applications as well as the stereoselective syntheses of all classes of phosphorus compounds has not yet been provided. This review reports the best stereoselective or asymmetric syntheses, the most efficient P*-building blocks and functionalisation of P-chirogenic compounds, in the light of chiral phosphorus compound applications. It is an extensive and useful documentation from pioneering work to recent advances in phosphorus stereochemistry

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

International audienceHuman immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs

Viral-induced neuroinflammation: Different mechanisms converging to similar exacerbated glial responses

There is increasing evidence that viral infections are the source/origin of various types of encephalitis, encephalomyelitis, and other neurological and cognitive disorders. While the involvement of certain viruses, such as the Nipah virus and measles virus, is known, the mechanisms of neural invasion and the factors that trigger intense immune reactions are not fully understood. Based on recent publications, this review discusses the role of the immune response, interactions between viruses and glial cells, and cytokine mediators in the development of inflammatory diseases in the central nervous system. It also highlights the significant gaps in knowledge regarding these mechanisms

Luminescent P-Chirogenic Copper Clusters

P-chirogenic dusters of the cubanes [Cu4I4L4] (L = chiral phosphine) were prepared from (+)- and (-)-ephedrine with L = (S)- or (R)-(R)(Ph)(i-Pr)P (with R = CH3 (seven steps) or C17H35 (10 steps)) with e.e. up to 96%. The X-ray structure of [Cu4I4((R)-(CH3)(Ph)(i-Pr)P)(4)] confirmed the cubane structure with average Cu center dot center dot center dot Cu and Cu center dot center dot center dot I distances of 2.954 and 2.696 angstrom, respectively. The cubane structure of the corresponding [Cu4I4((S)-(CH3)(Ph)(i-Pr)P)(4)] was established by the comparison of the X-ray powder diffraction patterns, and the opposite optical activity of the (S)- and (R)-ligand-containing clusters was confirmed by circular dichroism spectroscopy. Small-angle X-ray scattering patterns of one duster bearing a C17H35 chain exhibit a weak signal at 2 theta similar to 2.8 degrees (d similar to 31.6 angstrom), indicating some molecular ordering in the liquid state. The emission spectra exhibit two emission bands, both associated with triplet excited states. These two bands are assigned as follows: the high energy emission is due to a halide-to-ligand charge transfer, XLCT, state mixed with LXCT (ligand-to-halide-charge-transfer). The low energy band is assigned to a cluster-centered excited state. Both emissions are found to be thermochromic with the relative intensity changing between 77 and 298 K for the clusters in methylcyclohexane solution. Several differences are observed in the photophysical parameters, emission quantum yields and lifetimes for R = CH3 and C17H35. The measurements of the polarization along the emission indicate that the emission is depolarized, consistent with an approximate tetrahedral geometry of the chromophores

STLV-1 Commonly Targets Neurons in the Brain of Asymptomatic Non-Human Primates

The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established

Luminescent P‑Chirogenic Copper Clusters

P-chirogenic clusters of the cubanes [Cu₄I₄L₄] (L = chiral phosphine) were prepared from (+)- and (−)-ephedrine with L = (<i>S</i>)- or (<i>R</i>)-(R)­(Ph)­(<i>i</i>-Pr)P (with R = CH₃ (seven steps) or C₁₇H₃₅ (10 steps)) with e.e. up to 96%. The X-ray structure of [Cu₄I₄((<i>R</i>)-(CH₃)­(Ph)­(<i>i</i>-Pr)­P)₄] confirmed the cubane structure with average Cu···Cu and Cu···I distances of 2.954 and 2.696 Å, respectively. The cubane structure of the corresponding [Cu₄I₄((<i>S</i>)-(CH₃)­(Ph)­(<i>i</i>-Pr)­P)₄] was established by the comparison of the X-ray powder diffraction patterns, and the opposite optical activity of the (<i>S</i>)- and (<i>R</i>)-ligand-containing clusters was confirmed by circular dichroism spectroscopy. Small-angle X-ray scattering patterns of one cluster bearing a C₁₇H₃₅ chain exhibit a weak signal at 2θ ∼ 2.8° (<i>d</i> ∼ 31.6 Å), indicating some molecular ordering in the liquid state. The emission spectra exhibit two emission bands, both associated with triplet excited states. These two bands are assigned as follows: the high energy emission is due to a halide-to-ligand charge transfer, XLCT, state mixed with LXCT (ligand-to-halide-charge-transfer). The low energy band is assigned to a cluster-centered excited state. Both emissions are found to be thermochromic with the relative intensity changing between 77 and 298 K for the clusters in methylcyclohexane solution. Several differences are observed in the photophysical parameters, emission quantum yields and lifetimes for R = CH₃ and C₁₇H₃₅. The measurements of the polarization along the emission indicate that the emission is depolarized, consistent with an approximate tetrahedral geometry of the chromophores