Synthesis of Cyclopropanated [2.2.1] Heterobicycloalkenes: An Improved Procedure

<div><p></p><p>A safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. By using THF as the solvent and a more dilute aqueous NaOH solution for the generation of diazomethane from Diazald®, cyclopropanation could be achieved smoothly with minimal adjustment over the course of reaction. 7-Oxabicyclic substrates with bulky C1 or C2 groups, as well as 2,3-diazabicyclic substrates with various N-substituents effectively underwent cyclopropanation. Using this methodology, yields to previously reported products were markedly increased, and 10 new cyclopropanated [2.2.1] heterobicyclic products were prepared. In addition, this work accounts for the first reported cyclopropanation of 2,3-diazabicyclic alkenes, which all gave excellent yields of >90%.</p></div

Tunable Organophotocatalysts for Polymerization Reactions Under Visible Lights.

New organic photocatalysts derived from pyrene, anthracene, naphthacene, and pentacene are presented here for the formation of free radicals through a photoredox catalysis. These OPCs can work according to <i>an oxidative cycle</i> in a three component system in combination with diphenyl iodonium salt and a silane or in <i>a reductive cycle</i> in combination with amine and alkyl halide. This OPC behavior is highlighted through an investigation of the associated excited state and redox properties. The free radicals generated are characterized by ESR or photolysis experiments. Upon household LED bulb or Xe lamp exposure, the oxidative three-component system is able to promote the ring-opening polymerization ROP of an epoxide whereas the reductive three-component system is very efficient to initiate the free radical photopolymerization FRP of an acrylate. This ability of OPCs to initiate different polymerization reactions (ROP and FRP) is clearly an outstanding property

Organic Photocatalyst for Polymerization Reactions: 9,10-Bis[(triisopropylsilyl)ethynyl]anthracene

A new organic photocatalyst (9,10-bis­[(triisopropylsilyl)­ethynyl]­anthracene, <b>An-Si</b>) is proposed here for the formation of free radicals under very soft irradiation conditions under air through a photoredox catalysis. It works according to an oxidative cycle that uses the combination of <b>An-Si</b>, a diphenyl iodonium salt along with a silane. This behavior is highlighted through an investigation of its excited state and redox properties. The different chemical intermediates are characterized by ESR experiments. In addition, the reversibility of the oxidation reaction of <b>An-Si</b> was investigated by cyclic voltammetry. This three-component system is able to promote the ring-opening photopolymerization of an epoxide as well as the free radical photopolymerization of an acrylate upon household LED bulb and Xe lamp exposure. Excellent polymerization profiles (mainly in ROP) are obtained. The specific properties of this catalyst are outlined

Intramolecular Inverse Electron-Demand [4 + 2] Cycloadditions of Ynamides with Pyrimidines: Scope and Density Functional Theory Insights

4-Aminopyridines are valuable scaffolds for the chemical industry in general, from life sciences to catalysis. We report herein a collection of structurally diverse polycyclic fused and spiro-4-aminopyridines that are prepared in only three steps from commercially available pyrimidines. The key step of this short sequence is a [4 + 2]/<i>retro</i>-[4 + 2] cycloaddition between a pyrimidine and an ynamide, which constitutes the first examples of ynamides behaving as electron-rich dienophiles in [4 + 2] cycloaddition reactions. In addition, running the <i>ih</i>DA/<i>r</i>DA reaction in continuous mode in superheated toluene, to overcome the limited scalability of MW reactions, results in a notable production increase compared to batch mode. Finally, density functional theory investigations shed light on the energetic and geometric requirements of the different steps of the <i>ih</i>DA/<i>r</i>DA sequence

Iridium Photocatalysts in Free Radical Photopolymerization under Visible Lights

A series of iridium­(III) complexes was designed and investigated as new potential photocatalysts for radical polymerization reactions. The photocatalytic reduction cycle involves the combination of an iridium complex with an amine (e.g., <i>N</i>-methyldiethanolamine) and an alkyl halide (e.g., phenacylbromide). The different three-component systems herein investigated are very attractive for acrylate polymerization upon visible light irradiation. They are much more reactive than those based on Ru­(bpy)₃²⁺. Free radicals generated during the reaction were investigated by ESR spectroscopy and the chemical mechanisms are discussed. The crucial role played by the photocatalyst (reduction ability and excited state lifetime) is also demonstrated

Photopolymerization of Cationic Monomers and Acrylate/Divinylether Blends under Visible Light Using Pyrromethene Dyes

New photoinitiating systems based on boron-dipyrromethene dye (bodipy)/iodonium salt and optionally tris­(trimethylsilyl)­silane are proposed for the polymerization of divinylether and epoxy monomers upon visible-light exposure. The presence of the silane increases the epoxide rate of polymerization and conversion. Using acrylate/vinyl ether blends, the synthesis of cross-linked polymer networks (possessing two <i>T</i>_g values: −11 and 111 °C) is also successfully achieved through concomitant cationic and radical polymerization pathways. The chemical mechanisms associated with these initiating systems are investigated by steady-state photolysis and ESR experiments

Synthetic Variants of Mycolactone Bind and Activate Wiskott–Aldrich Syndrome Proteins

Mycolactone is a complex macrolide toxin produced by <i>Mycobacterium ulcerans</i>, the causative agent of skin lesions called Buruli ulcers. Mycolactone-mediated activation of neural (N) Wiskott–Aldrich syndrome proteins (WASP) induces defects in cell adhesion underpinning cytotoxicity and disease pathogenesis. We describe the chemical synthesis of 23 novel mycolactone analogues that differ in structure and modular assembly of the lactone core with its northern and southern polyketide side chains. The lactone core linked to southern chain was the minimal structure binding N-WASP and hematopoietic homolog WASP, where the number and configuration of hydroxyl groups on the acyl side chain impacted the degree of binding. A fluorescent derivative of this compound showed time-dependent accumulation in target cells. Furthermore, a simplified version of mycolactone mimicked the natural toxin for activation of WASP in vitro and induced comparable alterations of epithelial cell adhesion. Therefore, it constitutes a structural and functional surrogate of mycolactone for WASP/N-WASP-dependent effects

Synthetic Variants of Mycolactone Bind and Activate Wiskott–Aldrich Syndrome Proteins

Mycolactone is a complex macrolide toxin produced by <i>Mycobacterium ulcerans</i>, the causative agent of skin lesions called Buruli ulcers. Mycolactone-mediated activation of neural (N) Wiskott–Aldrich syndrome proteins (WASP) induces defects in cell adhesion underpinning cytotoxicity and disease pathogenesis. We describe the chemical synthesis of 23 novel mycolactone analogues that differ in structure and modular assembly of the lactone core with its northern and southern polyketide side chains. The lactone core linked to southern chain was the minimal structure binding N-WASP and hematopoietic homolog WASP, where the number and configuration of hydroxyl groups on the acyl side chain impacted the degree of binding. A fluorescent derivative of this compound showed time-dependent accumulation in target cells. Furthermore, a simplified version of mycolactone mimicked the natural toxin for activation of WASP in vitro and induced comparable alterations of epithelial cell adhesion. Therefore, it constitutes a structural and functional surrogate of mycolactone for WASP/N-WASP-dependent effects

Soft Photopolymerizations Initiated by Dye-Sensitized Formation of NHC-Boryl Radicals under Visible Light

A procedure for the production of N-heterocyclic carbene–boryl radicals (NHC-BH₂^•) upon visible light irradiation under soft conditions is presented. New acridine orange (dye)/diphenyl disulfide/NHC–BH₃ and dye/sulfonium salt/NHC–BH₃ three-component initiating systems are introduced for the efficient visible light photopolymerization of trimethylolpropane triacrylate. The new systems could be extendend to polymerization reactions in water (hydroxyethyl acrylate and hydroxyethyl methyl acrylate), which proceeded with strongly improved polydispersity. The chemical mechanisms are investigated through EPR and photolysis experiments

Grafting subdominant SM9 at GRA6_II C-terminus enhances its presentation, overturns the dominance hierarchy and provides efficient cyst control.

<p>(A) Schematic description of the GRA6_II-SM9 chimeric constructs. For GRA6_II-SM9_Cter, SM9 was introduced at the C-terminus, downstream of HF10. For GRA6_II-SM9_internal, SM9 was introduced internally within GRA6_II after residue 153, before the putative transmembrane domain. In both cases, SM9 was preceded by a leucine to mimic the endogenous flanking sequence of HF10. (B) Western blot analysis of GRA6 (upper panels) and SAG1 (loading control, lower panels) of the indicated parasite clones. (C,D) SM9 and HF10 presentation by BMDMs infected for 24 h with the indicated parasites, assessed with the BDSM9Z (C) and CTgEZ.4 (D) hybridomas, respectively. (E,F,G) <i>Ex vivo</i> evaluation of the CD8 responses and the parasite load 3 weeks post-infection with the indicated parasites. (E) IFN-γ intracellular staining of spleen cells restimulated with the SM9 peptide (left panel) or the HF10 peptide (right panel). (F) Tetramer staining of brain cells with SM9:L^d (left panel) and HF10:L^d (right panel). Bars represent the mean +/− SEM. Data pooled from 2 independent experiments. (G) Parasite burden in the brains of mice infected with control CEP (white bar), CEP+GRA6_II-SM9_internal (black bar) or CEP+GRA6_II-SM9_Cter (hatched bar), evaluated microscopically by enumerating the cysts. Histograms represent the mean +/− SEM of 14 mice per group, pooled from 3 independent experiments. *: <i>P</i><0.05 ; **: <i>P</i><0.005.</p