5 research outputs found

    Self-Assembled Asymmetric Catalyst Engaged in a Continuous-Flow Platform: An <i>Anti</i>-Selective Catalytic Asymmetric Nitroaldol Reaction

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    An <i>anti</i>-selective catalytic asymmetric nitroaldol reaction was manifested in a continuous-flow platform. The requisite Nd/Na heterogeneous catalyst was readily prepared by self-assembly of an amide-based chiral ligand, NdO<sub>1/5</sub>(O<sup><i>i</i></sup>Pr)<sub>13/5</sub>, NaHMDS, and a multiwalled carbon nanotube without covalent linkage. A stainless-steel column filled with the Nd/Na catalyst was incorporated in a flow system to promote the nitroaldol reaction with high stereoselectivity. The flow system with the heterogeneous catalyst obviated the quenching operation, and the cooling system was minimized

    A Modified Preparation Procedure for Carbon Nanotube-Confined Nd/Na Heterobimetallic Catalyst for <i>anti</i>-Selective Catalytic Asymmetric Nitroaldol Reactions

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    A recyclable asymmetric metal-based catalyst is a rare entity among the vast collection of asymmetric catalysts developed so far. Recently we found that the combination of a self-assembling metal-based asymmetric catalyst and multiwalled carbon nanotubes (MWNTs) produced a highly active and recyclable catalyst in which the catalytically active metal complex was dispersed in the MWNT network. Herein we describe an improved preparation procedure and full details of a Nd/Na heterobimetallic complex confined in MWNTs. Facilitated self-assembly of the catalyst with MWNTs avoided the sacrificial use of excess chiral ligand for the formation of the heterobimetallic complex, improving the loading ratio of the catalyst components. Eighty-five percent of the catalyst components were incorporated onto MWNTs to produce the confined catalyst, which was a highly efficient and recyclable catalyst for the <i>anti</i>-selective asymmetric nitroaldol reaction. The requisite precautions for the catalyst preparation to elicit reproducible catalytic performance are summarized. Superior catalytic profiles over the prototype catalyst without MWNTs were revealed in the synthesis of optically active 1,2-nitroalkanols, which are key intermediates for the synthesis of therapeutics

    Process Development for the Synthesis of a Selective M<sub>1</sub> and M<sub>4</sub> Muscarinic Acetylcholine Receptors Agonist

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    A practical and chromatography-free synthetic process to selective M<sub>1</sub> and M<sub>4</sub> muscarinic acetylcholine receptors agonist was developed and demonstrated on a several hundred gram scale. The key feature of this route is <i>N,N</i>-dimethylcarbamoylation of the anilinic nitrogen on the spiro 7-azaindoline structure via intermolecular migration of the <i>N,N</i>-dimethylcarbamoyl group. The resulting compound <b>1</b> was prepared in 43% overall yield with a chemical purity >99% via six steps starting with (2-chloropyridin-3-yl)­acetonitrile

    Image_1_Mesenchymal stem cell-derived exosomes for treatment of sepsis.jpeg

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    IntroductionThe pathogenesis of sepsis is an imbalance between pro-inflammatory and anti-inflammatory responses. At the onset of sepsis, the lungs are severely affected, and the injury progresses to acute respiratory distress syndrome (ARDS), with a mortality rate of up to 40%. Currently, there is no effective treatment for sepsis. Cellular therapies using mesenchymal stem cells (MSCs) have been initiated in clinical trials for both ARDS and sepsis based on a wealth of pre-clinical data. However, there remains concern that MSCs may pose a tumor risk when administered to patients. Recent pre-clinical studies have demonstrated the beneficial effects of MSC-derived extracellular vesicles (EVs) for the treatment of acute lung injury (ALI) and sepsis.MethodsAfter recovery of initial surgical preparation, pneumonia/sepsis was induced in 14 adult female sheep by the instillation of Pseudomonas aeruginosa (~1.0×1011 CFU) into the lungs by bronchoscope under anesthesia and analgesia. After the injury, sheep were mechanically ventilated and continuously monitored for 24 h in a conscious state in an ICU setting. After the injury, sheep were randomly allocated into two groups: Control, septic sheep treated with vehicle, n=7; and Treatment, septic sheep treated with MSC-EVs, n=7. MSC-EVs infusions (4ml) were given intravenously one hour after the injury.ResultsThe infusion of MSCs-EVs was well tolerated without adverse events. PaO2/FiO2 ratio in the treatment group tended to be higher than the control from 6 to 21 h after the lung injury, with no significant differences between the groups. No significant differences were found between the two groups in other pulmonary functions. Although vasopressor requirement in the treatment group tended to be lower than in the control, the net fluid balance was similarly increased in both groups as the severity of sepsis progressed. The variables reflecting microvascular hyperpermeability were comparable in both groups.ConclusionWe have previously demonstrated the beneficial effects of bone marrow-derived MSCs (10×106 cells/kg) in the same model of sepsis. However, despite some improvement in pulmonary gas exchange, the present study demonstrated that EVs isolated from the same amount of bone marrow-derived MSCs failed to attenuate the severity of multiorgan dysfunctions.</p
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