THE REGIOSPECIFICITY OF INTRAMOLECULAR N-3-BUTENYL NITRONE CYCLOADDITION

The reaction mechanism of the intramolecular cycloaddition of N-3-butenyl nitrone has been investigated theoretically by using AM1 MO method and transition state theory.There are two parallel reactions leading to two different regioisomers.The ratio of the rate constants of these two reactions was calculated to be 124.1(at 383.75 K).The obtained results can be used to explain the high regiospecificity of the reaction product.

Selective Deoxygenation of Nitrones Mediated by Sm/CoCl_26H_2O Reductive System

In the presence of metallic samariumcobalt (II) chloride hexahydrate, the nitrones can be reduced to the corresponding imines in moderate to high yields under mild and neutral conditions.

Solar Thermochemical Reactions IV: Unusual Reaction of Nitrones with Acetonitrile Derivatives Induced by Solar Thermal Energy

The behaviour of cyanothioacetamide 1 and the acetonitrile derivatives 6 and 10, respectively, towards the nitrones 2a-i induced by free solar thermal energy is reported. Structures and reaction mechanisms are also discussed.

Solvatochromism and Molecular Selectivity of C-(4-chlorophenyl)-N-phenylnitrone: A Photophysical Study

The ground state interaction of C-(4-chlorophenyl)-N-phenylnitrone (N1) with three different α, β-unsaturated ketones (K1 - K3) in very dilute solution (10-6 mol dm-3) has been noticed through charge transfer band formation in the visible region. The experimentally measured transition dipole, ground state resonance energy and formation constants of the complexes indicate interaction selectivity of the acyclic nitrone (N1) for the ketones. Molar absorptivity of the absorbing complexes were determined for all the three N1/K (1:1) interacting systems in toluene. Experimental findings were well rationalized with the help of electron density based global electrophilicity and nucleophilicity indices as well as with frontier molecular orbital calculations.

Stereoselective construction of azepine-containing bridged scaffolds via organocata-lytic bicyclization of yne-allenone esters with nitrones

A new organocatalytic double annulation cascade involving scission/recombination of N-O bonds of nitrones is reported for the first time, and used to produce a range of hitherto unprecedented tricyclic bridged-fused benzo[d]azepines bearing three stereogenic centers with moderate to good yields and complete diastereoselectivity. A quinine-catalyzed reaction of yne–allenone esters with nitrones worked well and provided a convergent and regioselective pathway to access these three-dimensional scaffolds from the planar conjugated system. Density functional theory(DFT) calculations have been applied to understand the key process for forming diradical intermediates.

Synthesis of a novel C-branched polyhydroxylated cyclic nitrone

A novel C-branched polyhydroxylated cyclic nitrone 25.which could be a valuable intermediate for the synthesis of C-branched pyrrolidine iminosugars,was synthesized starting from the commercially available i.-arabinose in 29.0%total yield.

Synthesis of 5-Fluoroalkyl Isoxazolidines via 1,3-Dipolar Cycloaddition of Ethyl 2-Hydropolyfluoroalk-2- enoates with Nitrones

Dipolar cycloaddition reactions of ethyl 2-hydropolyfluoroalk-2-enoates (1) with some nitrones were de-scribed. The reaction of 3,4-dihydroisoquinoline N-oxide (2) with 1 took place readily in methylene chloride at room temperature to give the corresponding 5-fluoroalkylisoxazolidines regioselectively as a mixture of two di-astereoisomers (trans and cis) in high yields, while longer reaction time and higher temperature were needed in the case of non-cyclic nitrones. Under similar conditions the reaction of quinoline N-oxide (14) with 1 did not give the expected adducts and a ring-opening product was obtained.

Nitronic 50不锈钢低温冲击韧性大幅降低原因分析

针对低温风洞运动机构用Nitronic 50奥氏体不锈钢在复检中出现低温冲击吸收能量显著偏低的现象,对该批次不锈钢和参考样品分别取样,进行了化学成分、金相、扫描电镜以及能谱等分析。结果表明:该批次Nitronic 50不锈钢中存在大量短棒状的Al N脆性夹杂物,是导致其低温冲击韧性大幅度降低的主要原因;材料晶粒尺寸偏大且存在混晶现象也降低了其冲击韧性。

TBN improves motor function and prolongs survival in SOD1G93A and TDP-43M337V mouse model of amyotrophic lateral sclerosis

OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative dis⁃ease characterized by progressive loss of upper and lower motor neurons that results in skeletal muscle atrophy,weakness and paralysis.Oxida⁃tive stress plays a key role in the pathogenesis of ALS,including familial forms of the disease arising from mutation of the gene coding for superoxide dismutase 1(SOD1).Moreover,although the pathogenesis of ALS is unclear,the abnormal accumulation of TAR DNA-binding pro⁃tein of 43 ku(TDP-43)is a pathological feature that exists in almost all patients.Thus far,there is no drug that can cure ALS/FTLD.Tetramethyl⁃pyrazine nitrone(TBN)is a derivative of tetra⁃methylapyrazine,derived from the traditional Chinese medicine Ligusticum chuanxiong,which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases.TBN is currently under clinical investi⁃gation for several indications including a phaseⅡtrial of ALS.Here,we explored the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse model.METHODS In the SOD1G93A transgenic mouse model,TBN was administered to mice by intraperitoneal or intragastric injection after the onset of motor deficits.At the same time,we unilaterally and bilaterally injected the TDP-43M337V virus into the striatum of the WT mouse,and gave the TBN treatment after the mice developed a phenotype.After administering these two models for a period of time,we con⁃ducted behavioral tests,including rotarod test,balance beam test,climbing pole test,etc,to evaluate the efficacy of TBN on SOD1G93A and TDP-43M337V models.Furthermore,we explored the possible mechanism of action of TBN in the treatment of ALS through Western blotting and immunohistochemistry/immunofluorescence staining analysis.RESULTS In the SOD1G93A transgenic mouse model,TBN slowed the pro⁃gression of motor neuron disease as evidenced by improved motor performance,reduced spinal motor neuron loss and the associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.What′s more,in the TDP-43M337V mice model,the results showed that in mice with unilateral injection of TDP-43M337V,TBN improved motor deficits and cognitive im⁃pairment in the early stages of disease progres⁃sion.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival rate.Moreover,we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3βand AMPK/PGC-1α/Nrf2 signaling pathways.In summary,TBN is a promising agent for the treat⁃ment of ALS/FTLD.CONCLUSION TBN has shown good efficacy in both SOD1 and TDP-43 ALS-related models,and it may act by activating the AMPK/PGC-1α/Nrf2 signaling pathway,which shows some light for the development of ALS therapeutic drugs.

A Novel Synthesis of Isoxazole Derivatives

The new synthetic method of isoxazole derivatives was succesfully achieved. The experimental results demonstrate that thermal decomposition reactions of nitrone could take place with yields of 41 similar to 81%, to give a series of new isoxazole derivatives.

Studies on New Additions to 5-Methoxy-2 (5H)-Furanone: 1, 4-Addition of Grignard Reagents, and 1,3-Dipolar Cycloaddition of Silyl Nitronates

1,4-Addition reaction of Grignard's reagent to 5-methoxy-2(5H)-furanone 1 was accomplished. which provided a new possible route for synthesizing beta -alkyl-Y-alkyloxy-Y-butyrolactone. A novel concise method of preparing fused heterocyclic compounds was offered by 1,3-dipolar cycloaddition reaction of silyl nitronates to 1.

Analysis of the Composition and Physical and Mechanical Properties of Raw Materials for Thermal Insulation Fabrics

In this article, winter clothes, bedding, pillows, mattresses are produced in the Republic of Uzbekistan and used in the export products of foreign countries in domestic market shopping centers;existing nonwoven fabric samples were used as toys, children’s clothing as a heat retainer, a space-filler was selected on the basis of marketing survey analysis. Chemical bonding, processing technology, methods, linear density, thickness, air permeability, hygroscopicity, heat storage and heat transfer properties of the samples were analyzed experimentally based on the preparation methods, the fiber content was compared with the standard technology. The advantages and disadvantages of the samples were studied and recommendations for use in sewing according to consumer requirements were given.

Asymmetric 1,3-Dipolar Cycloaddition of the Chiral Nitronic Esters with Acrylate

Asymmetric 1,3-dipolar cycloaddihon of the chiral nitronic esters with acrylate giving the enantiomerically pure novel chiral bisheterocyclic compounds is describcd

Benzisoxazole core and benzoxazolopyrrolidine via HDDA-derived benzyne with PTIO/DMPO

A novel method for HDDA-derived benzyne trapped by nitrone was developed. This research described a simple and efficient pathway for the synthesis of benzisoxazoles from arynes and PTIO(2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl), C-C and C-O bonds were formed in a single step without catalyst under mild conditions. The unexpected cleavage of C-N bond contributed to the formation of isoxazole ring, as indicated by DFT studies. Furthermore, we obtained the structure of benzoxazolopyrrolidine when the trapping agent is DMPO(5,5-dimethyl-1-pyrroline N-oxide).

Nitronic50奥氏体不锈钢的热变形行为

在变形温度为950~1150℃,应变速率为0.01~10 s^(-1)、工程应变量为0.6的条件下,通过Gleeble-3800热模拟试验机对Nitronic50奥氏体不锈钢进行了单道次热压缩变形试验。通过引用Zener-Hollomon参数,对Nitronic50钢进行了本构方程的构建,不同变形条件下计算得到的峰值应力值与实际峰值应力值吻合程度较高。通过动态材料模型绘制了Nitronic50钢的能量耗散图,并结合变形后的组织发现能量耗散低反而易于得到较好的热变形组织,本试验条件下最佳的热变形工艺为变形温度在1000℃附近,变形速率1~10 s^(-1)。

Gold（Ⅰ）-Catalyzed Diastereo- and Enantioselective Synthesis of Polysubstituted Pyrrolo[3,4-d][1,2 ]oxazines

A gold（I）-catalyzed highly diastereo- and enantioselective intermolecular cycloaddition of oxime ethers with nitrones under mild conditions was developed, which provides an facile access to optically pure highly substituted pyrrolo[3,4-d][1,2]oxazines. The salient features of this reaction in- clude general substrate scope, high efficiency, high enantioselectivity, readily available starting materials, and the use of commercially available ligand.

Novel approaches to combat chemoresistance against glioblastomas

The poor prognosis of glioblastoma multiforme(GBM)patients is in part due to resistance to current standard-of-care treatments including chemotherapy[predominantly temozolomide(TMZ;Temodar)],radiation therapy and an anti-angiogenic therapy[an antibody against the vascular endothelial growth factor(bevacizumab;Avastin)],resulting in recurrent tumors.Several recurrent GBM tumors are commonly resistant to either TMZ,radiation or bevacizumab,which contributes to the low survival rate for GBM patients.This review will focus on novel targets and therapeutic approaches that are currently being considered to combat GBM chemoresistance.One of these therapeutic options is a small molecule called OKlahoma Nitrone 007(OKN-007),which was discovered to inhibit the transforming growth factor β1 pathway,reduce TMZ-resistance and enhance TMZ-sensitivity.OKN-007 is currently an investigational new drug in clinical trials for both newly-diagnosed and recurrent GBM patients.Another novel target is ELTD1(epidermal growth factor,latrophilin and seven transmembrane domain-containing protein 1;alternatively known as ADGRL4,Adhesion G protein-coupled receptor L4),which we used a monoclonal antibody against,where a therapy against it was found to inhibit Notch 1 in a pre-clinical GBM xenograft model.Notch 1 is known to be associated with chemoresistance in GBM.Other potential therapeutic targets to combat GBM chemoresistance include the phosphoinositide 3-kinase pathway,nuclear factor-κB,the hepatocyte/scatter factor(c-MET),the epidermal growth factor receptor,and the tumor microenvironment.

Synthesis of Novel Fuctionalized Glycosides Based on 1,3-Dipolar Cycloaddition

1 Results 1,3-Dipolar cycloaddition reaction is one of the most common methods for preparing various five membered heterocycles,and provides a conveniet protocols for constructing C-C bond with functional groups.The reaction has also been successfully used in the syntheses of C-glycosides and other sacharride derivatives.We wish to present herein our recent approaches on the synthesis of novel C-amino-glycosides,C-aminodisaccharides,spiro heterocyclic glycosides and heterocycle linked C-disaccharides,et...

Synthesis and glycosidase inhibition of C-7 modified casuarine derivatives

A series of C-7 modified analogues of casuarine have been synthesized from sugar-derived nitrone and assayed against various glycosidases. Introduction of C-7 aminomethyl or amide group led to sharp decrease of the inhibitory activities.

Synthesis of a-carbethoxy substituted chiral alkyl nitronic esters

Of organic compounds,nitronic esters are a group of unusual compounds.Accordingto their chemical formula（R1R2C=NO2R3）,they might be formally obtained fromcondensation of aci-nitro compounds（intronic acids）and alcohols with an equivalentamount of water eliminated.In fact,neither could nitronic esters be produced by thismethod,nor could they be hydrolyzed into nitronic acids and alcohols.Since they