Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of organoboronic acids with N-protected 4-iodophenyl alanine linked isoxazoles

Suzuki-Miyaura coupling reaction of N-protected 4-iodopheyl alanine isoxazoles with arylboronic acids,catalyzed by palladium,efficiently produce benzyl-N-（4-bipheyl）-2-（3-methyl-5（E）-2-aryl-1-ethenyl-4-isoxazolyl）-amino-2-oxoethyl）carba- mates in good yields.This process is first of its kind to construct carbon-carbon bond formation having biaryl motif on amino acid linked isoxazole moiety.

Traceless solid-phase synthesis of 3-substituted isoxazoles from polystyrene-supported vinyl selenide

A novel facile procedure for traceless solid-phase synthesis of 3-substituted isoxazoles in good yields and with excellent purities using polymer-supported vinyl selenide has been developed.

Copper Nitrate-Mediated Selective Bond Cleavage of Alkynes:Diverse Synthesis of Isoxazoles

An unprecedented copper nitrate-mediated bond cleavage of alkynes was developed for the modular synthesis of isoxazoles,where either C—S bond or C≡C triple bond was cleaved selectively.Substituents attached to the C≡C triple bonds could differentiate the chemical bonds cleavage and reaction pathways disparately.Various transformations of products illustrate promising applications of the given protocols.

Ru(Ⅲ)-catalyzed construction of variously substituted quinolines from 2-aminoaromatic aldehydes(ketones)and isoxazoles:Isoxazoles as cyclization reagent and cyano sources

A Ru(Ⅲ)-catalyzed annulation reaction of 2-aminoaromatic aldehydes(ketones)and isoxazoles to afford diverse 3-cyanoquinolines has been developed.Notably,isoxazole acted as a cyclization reagent and nontoxic cyano source via N-O bond cleavage and fragmentation.Variously substituted(especially 6-or 7-substituted)quinolines could be easily afforded.This procedure features wide functional group compatibility,efficiency and avoiding toxic cyano source.Meanwhile,this protocol could be successfully applied to scale-up synthesis.Further chemical transformations of 3-cyanoquinoline could give some valuable skeletons,demonstrating its potential in synthetic application.

Synthesis and Herbicidal Activities of 3-(Substituted phenyl)isoxazole Derivatives

Several novel 3-(substituted phenyl)isoxazole derivatives were prepared from phenyl butan-1,3-dione. Their structures were confirmed by 1H NMR, IR, and CIMS. Preliminary bioassay showed that some of them exhibited good activities toward various weeds.

Design,Synthesis and Insecticidal Activities of Novel Phenyl Substituted Isoxazolecarboxamides

Thirteen novel phenyl substituted isoxazolecarboxamides were synthesized, and their structures were characterized by IH NMR, elementary analysis and high-resolution mass spectrometry（HRMS） techniques. Their evaluated insecticidal activities against oriental armyworm（Mythimna separata） indicate that the phenyl substituted isoxazolecarboxamides exhibited moderate insecticidal activities, among which compounds 9c and 9k showed com- paratively higher activities.

Novel insights on acetylcholinesterase inhibition by Convolvulus pluricaulis,scopolamine and their combination in zebrafish

Acetylcholinesterase(AChE)inhibitors increase the retention of acetylcholine(ACh)in synapses.Although they allevi-ate cognitive deficits in Alzheimer’s disease,their limited benefits warrant investigations of plant extracts with similar properties.We studied the anti-AChE activity of Convolvulus pluricaulis(CP)in a zebrafish model of cognitive impair-ment induced by scopolamine(SCOP).CP is a perennial herb with anti-amnesiac and anxiolytic properties.It contains alkaloid,anthocyanin,coumarin,flavonoid,phytosterol and triterpenoid components.Isoxazole(ISOX)was used as a positive control for AChE inhibition.CP-treated 168 hpf larvae showed a similar pattern of AChE inhibition(in the myelencephalon and somites)as that of ISOX-treated larvae.CP was superior to ISOX as evidenced by the retention of avoidance response behavior in adult zebrafish.Molecular docking studies indicated that ISOX binds Ser203 of the catalytic triad on the human AChE.The active components of CP-scopoletin and kaempferol-were bound by His447 of the catalytic triad,the anionic subsite of the catalytic center,and the peripheral anionic site.This suggested the ability of CP to mediate both competitive and non-competitive modes of inhibition.Surprisingly,SCOP showed AChE inhibition in larvae,possibly mediated via the choline-binding sites.CP+SCOP induced a concentration-dependent increase in AChE inhibition and ACh depletion.Abnormal motor responses were observed with ISOX,CP,ISOX+SCOP,and CP+SCOP,indicative of undesirable effects on the peripheral cholinergic system.Our study proposes the examination of CP,SCOP,and CP+SCOP as potential AChE inhibitors for their ability to modulate cognitive deficits.

Basic fibroblast growth factor increases the numbe of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice

This study aimed to investigate the number of amino methyl isoxazole propionic acid （AMPA） receptors and production of endogenous neural stem cells in the SOD1 G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor （FGF-2）. A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice.

Some New Heterocycles from the Reaction of 4-Carboxaldehyde-2-Phenyl-2H-1,2,3-Triazole Malononitrile

Reaction of 4-carboxaldehyde-2-phenyl-2H-1,2,3-triazole 1 with malononitrile in presence of piperidine afforded the triazolomalonitrile 2 which on treatment with hydrazine hydrate, gave 3-amino-5-(2-phenyl-2H-1,2,3-triazol-4-yl)-4,5-dihydro-1-H-pyrazole-4-carbonitrile 3 and with hydroxylamine, gave 5-amino-3-(2-phenyl-2H-1,2,3-triazol-4-yl)-2,3-dihydroisoxazole-4-carbonitrile 4, and with thiourea, gave?2,4-diamino-6-(2-phenyl-2H-1,2,3-triazol-4-yl)-6H-1,3-thiazine-5-carbonitrile 5. Similarly, reaction of 2 with ethanol amine, gave 2-amino-4-(2-phenyl-2H-1,2,3-triazol-4-yl)nicotinonitrile 6, and with thiosemicarbazide,?gave 4-amino-2-hydrazinyl-6-(2-phnyl-2H-1,2,3-triazol-4-yl)-6H-1,3-thiazine-carbonitrile?7. Similary reaction of 2 with cyclopentanone gave, 2-amino-4-(2-phenyl-2H-1,2,3-triazol-4-yl)-4,5,6,7-tetrahydrocyclopenta [6] pyran-3-carbonitrile 8. In addition, reaction of 1 with hydrazine hydrate, gave the 4 hydrazone which on treatment with another mole of 1 gave 10 and with 3-carboxaldehyde-1-phenyl-4,5-pyrazolinedione 4 phenylhydrazone gave compound 11.

Synthesis and Spectral Identification of Novel Stable Triazene: As Raw Material for the Synthesis Biocompatible Surfactants-Pyrazole-Isoxazole-Dihydropyrimidine-Tetrahydropyridine Derivatives

The chemical reactivity of novel stable triazene 3 toward some nucleophilic and electrophilic reagents was investigated. Traizene 3 was used as a key precursor for the synthesis of some novel important heterocyclic compounds such as Pyrazole, Isoxazole, Dihydropyrimidine, Tetrahydro-pyridine derivatives with expected antimicrobial activity. The synthesized compounds were obtained in good yields. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H-NMR and Ms spectral data.

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.

Ferrocenyl-isoxazole Derivative： a Novel Electrochemical, Colorimetric and Fluorescent Multiple Signal Probe for Highly Selective Recognition of Cu2＋ Ions

In this paper, a novel compound 3-（2-qninolyl）-5-ferrocenyl-isoxazole（5） with high selectivity toward Cu2＋ over other heavy and transition-metal（HTM） ions was designed and synthesized in good yields. The compound not only could be used as an electrochemical probe for Cu2＋ with an anodic peak shift of Fe（II）/Fe（III） redox couple, but also could be a colorimetric and fluorescent probe due to the detectable change in color by naked eyes and a significant fluorescence quenching of monomeric anthracene moiety. This highly selective sensing of Cu2＋ may be attributed to the unprecedented intermolecular electron-transfer reorganization after the oxidation of the first single electron of compound 5, as indicated by electrospray ionization mass spectrometry（ESI-MS） and density functional theory（DFT） calculation results. To the best of our knowledge, this class of compounds have rarely been reported in the field of molecular sensing. It may have a potential significance for the application of the ferrocenyl-isoxazole derivative in molecular recognition.

Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

A series of novel pyridinyl-4,5-2H-isoxazole derivatives was synthesized and their chemical structures were characterized by 1H NMR, 13C NMR as well as MS spectroscopic methods, their melting points were also determined. The inhibitory effects of them against breast cancer cell lme（MCF-7） were evaluated by 3-（4,5-dimethyl- 2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（MTT） procedure in vitro. Most of them possesed potent anti- proliferative activities, among which compounds llc and llj exhibited half maximal inhibitory concentrations（IC50） of 1.9 and 1.5 μmol/L, respectively. These compounds also exhibited potent anti-proliferative activities against both human hepatoma cell line（HepG2） and cervical cancer cell line（HeLa）. Preliminary structure-activity relationship （SAR） information from these compounds can be used to guide further exploration of new compounds with better potency as molecular probes. Further study on the mechanism-of-action of these compounds is under investigation.

Microwave Assistant Synthesis and Crystal Structures of Two Substituted Oxazole Isoxazole Carboxamides

Two novel substituted phenyl oxazole isoxazole carboxamides have been synthesized by microwave assistant technology.The target compounds were characterized by IR,1H NMR,13C NMR and HRMS,and their single-crystal structures were further determined by X-ray diffraction.3-Phenyl-4-(2΄-methyl-2΄-isopropyl-1΄,3΄-oxazole)-5-methyl isoxazole carboxamide(6a)crystallizes in monoclinic system,space group P21/c with a=6.2137(12),b=19.923(4),c=13.748(3)Å,β=92.30(3)°,V=1700.6(6)Å3,Dc=1.228 Mg/m3,Z=4,F(000)=672,μ(MoKα)=0.084 mm-1,R=0.0526 and wR=0.1259.3-(2΄-Fluoro-6΄-chloro-phenyl)-4-(2΄-methyl-2΄-ethyl-1΄,3΄-oxazole)-5-methyl isoxazole carboxamide(6b)crystallizes in triclinic system,space group P with a=7.8750(16),b=10.596(2),c=11.725(12)Å,β=102.05(3)°,V=859.5(3)Å3,Dc=1.363 Mg/m3,Z=2,F(000)=368,μ(MoKα)=0.250 mm-1,R=0.0738 and wR=0.1941.Both of the molecules prefer to form crystal packing through C–H…O hydrogen bonds.Compounds 6a and 6b show safener activity on maize against the injury of chlorsulfuron.

Microwave-assisted Synthesis of New 1,2,3-Triazoles Bearing an Isoxazole Ring by the Azide-alkyne Cycloaddition Click Chemistry

A comparison synthesis of 1,2,3-triazoles bearing isoxazole ether was developed between conventional and microwave-assisted heating. Single/donble 1,2,3-triazoles bearing isoxazole ether were synthesized by click reaction starting from substituted isoxazolyl alkyne compounds and substituted benzyl azide compounds or neopen- tylglycol diazide in the presence of copper（I） that in-aim generated. Herein, the effect of different catalysts on the yield was researched by conventional method, and the optimal catalyst was selected. The structures of all the synthe- sized compounds were confirmed by MS, FTIR, ^1H and ^13C NMR spectroscopies. Moreover, the crystal structure of 5-{[（1-benzyl-1H-1,2,3-triazol-4-yl）methoxvlmethvl}-3-（4-fluoroohenvl）isoxazole（2h） was determined.

Synthesis and Liquid Crystalline Properties of 3-Substituted Pentane-2,4-dione, Pyrazole and Isoxazole Derivatives

The γ-substituted β-diketonate 2,4-dioxo-3-pentyl 4-[4-（n-octyloxy）cinnamoyl]oxybenzoate 1 and its pyrazole and isoxazole derivatives （2 and 3 respectively） have been synthesized and characterized by the spectroscopic methods and elemental analysis. The mesogenic properties of these compounds have been studied by polarizing optical microscopy （POM） and differential scanning calorimetry （DSC）. A monotropic nematic mesophase was observed for the β-diketonate 1, in contrast, the pyrazole 2 displays an enantiotropic smectic A and isoxazole 3 exhibits an enantiotropic nematic mesophase. The relationship between the structure and liquid crystalline properties has also been discussed.

Design, Synthesis and Biological Activities of Novel Anthranilic Diamides Containing Dihydroisoxazoline and Isoxazole

Anthranilic diamides are one of the most important classes of modern agrochemical insecticides. To discover new structures with higher activity, lower toxicity and lower residue, a series of novel anthranilic diamides containing dihydroisoxazoline and isoxazole was designed and synthesized. Their structures were characterized by means of melting points, proton nuclear magnetic resonance（IH NMR）, 13C NMR and high resolution mass spectrometry（HRMS）. According to the bioassay data, it was found that some of the title compounds exhibit moderate insecticidal activity and good antifungal activity. In particularly, compound 15b with a concentration of 50 mg/L shows a lethality rate of 60.0% against Mythimna separata Walker and a lethality rate of 50.0% against Culex pipiens pallens with a concentration of 1 mg/L. Moreover, compound 15b showed good antifungal activities（58.8%, 77.1%, 70.7%, 55.3%, 60.7%, 65.4%） when against all the tested fungi（Cercospora araehidicola tIori, Physalospora piricola, Rhizoctonia cerealis, Bipolaris maydis, Watermelon anthracnose, Fusarium moniliforme）. The effects of compounds 14h, 14j and 15b on the concentration of intracellular calcium ion（[Ca2＋]i） in the central neurons of Mythimna separate Walker were well investigated via calcium imaging technique. The results demonstrate that the novel compounds can elevate the calcium concentration in the neurons, denoting that some new structures are potential modulators of the insect ryanodine receptor（RyR）.

Insight into the Structural Requirements of Protoporphyrino- gen Oxidase Inhibitors： Molecular Docking and CoMFA of Di- phenyl Ether, Isoxazole Phenyl, and Pyrazole Phenyl Ether

Protoporphyrinogen oxidase （PPO, EC 1.3.3.4） is one of the most significant targets for a large family of in- hibitors that may be used as herbicide, bactericide, fungicide, or photosensitizing activator to treat cancer through photodynamic therapy （PDT）. Molecular docking and CoMFA were combined in a multistep framework with the ultimate goal of identifying important factor contributing to the activity of PPO inhibitors. As a continuation of the previous research work on the development of new PPO inhibitors, the bioassay results indicated that good PPO in- hibitors were discovered in all of the three chemical series with ICs0 values ranging from 0.010 to 0.061 pmol·L ^-1. Using the crystal structure of tobacco mitochondrial PPO （mtPPO） as template, all the compounds were docked into the enzyme active site. The docking pose of each compound was subsequently used in a receptor-based alignment, leading to the development of a significant CoMFA model with r^2 value of 0.98 and q^2 （cross validation r^2） value of 0.63. This novel multistep framework gives insight into the and it can be extended to other classes of PPO inhibitors. In be particularly applicable in virtual screening procedures. structural characteristics for the binding of inhibitors, addition, the simplicity of the proposed approach may

Microwave-assistant Syntheses, Crystal Structures and Safener Activities of Two Substituted Phenyl Isoxazole Derivatives

Two novel substituted phenyl isoxazole benzoxazine formamide derivatives were designed and synthesized with substituted o-aminophenol,1,2-dibromoethane and different phenyl substituted isoxazole formyl chloride as the raw materials via microwave assistant synthesis.The target compounds were characterized by IR,^(1)H NMR,^(13)C NMR and HRMS.Both single-crystal structures were further determined by X-ray diffraction.3-(2’-Chloro-6’-fluoro-phenyl)-4-(2’,3’-dihydro-1’,4’-benzoxazine)-5-methyl-isoxazole formamide (4a) crystallizes in orthorhombic system,P2_(1) space group with a=8.9414(18),b=10.834(2),c=17.706(4)A,V=1715.1(6)A^(3),D_(c)=1.444 Mg/m^(3),Z=4,F(000)=768,μ(Mo Kα)=0.255 mm^(-1),R=0.0406 and wR=0.1171.3-Phenyl-4-(6-methyl-2’,3’-dihydro-1’,4’-benzoxazine)-5-methyl-isoxazole formamide (4b) is of triclinic system,space group PI with a=7.7659(16),b=8.3626(17),c=13.484(3)A,α=76.04(3)°,β=100.63(3)°,γ=82.01(3)°,V=841.6(3)A^(3),D_(c)=1.319 Mg/m^(3),Z=2,F(000)=352,μ(Mo Kα)=0.090 mm^(-1),R=0.0672 and wR=0.2671.Both crystals are packed through C–H···O hydrogen bonding interaction.There is C–H···F hydrogen bond between 4a molecules,and C–H···N between 4b molecules.Bioassay results showed that compounds 4a and 4b exhibited detoxification on maize and restored maize growth index.