34 research outputs found

    Azetidine synthesis by La(OTf)3-catalyzed intramolecular regioselective aminolysis of cis-3,4-epoxy amines

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    Azetidine is a prevalent structural motif found in various biologically active compounds. In this research paper, we report La(OTf)3-catalyzed intramolecular regioselective aminolysis of cis-3,4-epoxy amines to afford azetidines. This reaction proceeded in high yields even in the presence of acid-sensitive and Lewis basic functional groups

    Ecdysone-dependent and ecdysone-independent programmed cell death in the developing optic lobe of Drosophila

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    AbstractThe adult optic lobe of Drosophila develops from the primordium during metamorphosis from mid-3rd larval stage to adult. Many cells die during development of the optic lobe with a peak of the number of dying cells at 24h after puparium formation (h APF). Dying cells were observed in spatio-temporal specific clusters. Here, we analyzed the function of a component of the insect steroid hormone receptor, EcR, in this cell death. We examined expression patterns of two EcR isoforms, EcR-A and EcR-B1, in the optic lobe. Expression of each isoform altered during development in isoform-specific manner. EcR-B1 was not expressed in optic lobe neurons from 0 to 6h APF, but was expressed between 9 and 48h APF and then disappeared by 60h APF. In each cortex, its expression was stronger in older glia-ensheathed neurons than in younger ones. EcR-B1 was also expressed in some types of glia. EcR-A was expressed in optic lobe neurons and many types of glia from 0 to 60h APF in a different pattern from EcR-B1. Then, we genetically analyzed EcR function in the optic lobe cell death. At 0h APF, the optic lobe cell death was independent of any EcR isoforms. In contrast, EcR-B1 was required for most optic lobe cell death after 24h APF. It was suggested that cell death cell-autonomously required EcR-B1 expressed after puparium formation. βFTZ-F1 was also involved in cell death in many dying-cell clusters, but not in some of them at 24h APF. Altogether, the optic lobe cell death occurred in ecdysone-independent manner at prepupal stage and ecdysone-dependent manner after 24h APF. The acquisition of ecdysone-dependence was not directly correlated with the initiation or increase of EcR-B1 expression

    The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice

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    Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice

    The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice

    Get PDF
    Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice

    Chromium–Salen Complex / Nitroxyl Radical Cooperative Catalysis:A New Combination for Aerobic Intramolecular Dearomative Coupling of Phenols

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    Herein we describe an aerobic intramolecular dearomative coupling reaction of phenols using a catalytic system with the combination of a chromium–salen (Cr–salen) complex and a nitroxyl radical. This novel catalytic system enables the construction of a spirocyclic dienone product, which is a potentially useful intermediate for the synthesis of various natural products such as alkaloids and phenylpropanoids from bisphenol in good yield under mild reaction conditions (under O2 and ambient temperature). A preliminary mechanistic study suggests that this reaction system is promoted by a cooperative electron transfer between the Cr(III)–salen complex, nitroxyl radical and bisphenol substrate

    Highly conformal and high-ionic conductivity thin-film electrolyte for 3D-structured micro batteries: Characterization of LiPON film deposited by MOCVD method

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    This paper reports a lithium phosphorus oxynitride (LiPON) thin-film electrolyte deposited using a metalorganic-chemical vapor deposition (MOCVD) method for 3D-structured micro batteries. It is shown that the MOCVD-LiPON film has both highly-conformal step coverage on a patterned substrate with line/space=2μm/2μm and aspect ratio=1 (51±3 nm) and high-ionic conductivity for very thin films deposited at 4.7 nm/min (5.9×10-6 S/cm for 190 nm and 5.3×10-6 S/cm for 95 nm). Detailed material characterization attributes the enhancement in ionic conductivity to a decrease in nanocrystallite size and improvement in chemical-composition uniformity in the film. In addition, electrochemical characterization of an all-solid-state thin-film battery fabricated with the 190 nm-thick LiPON film (Si substrate/Ti/Pt/LiCoO2/LiPON/a-Si:H/Cu) demonstrates that the LiPON film can successfully act as the electrolyte for lithium-ion batteries. Therefore, the MOCVD-LiPON film is a promising candidate material to realize 3D-structured micro batteries in the near future
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