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.

Synthesis of Trisubstituted Isoxazoles from Nitroenamines and Aromatic Aldehydes

A novel approach for the synthesis of trisubstituted isoxazoles from nitroenamines and aromatic aldehydes is developed. L-Proline/potassium carbonate system was employed to promote this process. The reaction underwent nucleophilic attack of nitroenamines to aromatic aldehydes, intramolecular denitration, tautomerization and elimination of H2O to furnish the target compounds.

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.

An Efficient Deselenenylation Reaction to the Synthesis of 3, 5-Disubstituted Isoxazoline and Isoxazole

A mild deselenenylation reaction protocol for the preparation of 3, 5-disubstituted isoxazolines and their further application to 3-methyl-5-substituted isoxazoles both in solution phase and solid phase was reported.

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.

The Smallest Monofluorodiazoethane Reagent and Its[3+2]Cycloaddition Reactions

Given the widespread applications of fluorinated substances in pharmaceuticals,biology,and materials,the development of fluorine-containing building blocks remains an important topic in organic chemistry.In the repertoire of fluorinated diazo compounds,research on tri-and difluorodiazoethane is well-established,but the lack of synthetic methods has left studies related to monofluorodiazoethane as an unexplored territory.In our current work,the taming of the smallest monofluorodiazoethane reagent was realized using two phenylsulfonyl mask groups.This newly synthesized diazo reagent displayed intriguing reactivity patterns:the reaction with aryldiazonium salts gave monofluoromethyl tetrazoles,whereas its reactivity with alkynes and alkenes furnished monofluoromethyl isoxazoles and dihydro-isoxazoles.Furthermore,the removal of the masking groups provided access to a wide range of monofluoromethyl-functionalized heterocycles.

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.

A Fast and Highly Efficient Protocol for Reductive Amination of Aromatic Aldehydes Using NaBH4 and Isoxazole Amines in an Ionic Liquid Medium

Reductive amination of aromatic aldehydes using NaBH4 and isoxazole amines is carried out in a Bronsted acidic ionic liquid 1 -methylimidazolium tetrafluoroborate [（HMIm）BF4]. The ionic liquid plays dual roles of solvent as well as catalyst for the efficixcellent yields without any undesired side product formation. The newly synthesized compoundsent transformation of aromatic aldehydes to heterocyclic substituted amines in e （3, 6 and 7） were characterized by IR, 1H NMR and mass spectral techniques.

The convenient synthesis of 4-arylmethylidene-4,5-dihydro-3-phenylisoxazol-5-ones

4-Arylmethylidene-4,5-dihydro-3-phenylisoxazol-5-ones were synthesized by the convenient three-component reaction of ethyl benzoylacetate,hydroxylamine and aromatic aldehydes in the presence of pyridine.The target compounds were also obtained by the reaction between 3-phenylisoxazol-5-one and aromatic aldehydes at 105℃under solvent free condition.Yields of products depended considerably on the aldehyde used.

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.