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...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.展开更多
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 sou...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.展开更多
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.
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...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.展开更多
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...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.展开更多
Lithium-ion batteries are widely recognized as prime candidates for energy storage devices.Ethylene carbonate(EC)has become a critical component in conventional commercial electrolytes due to its exceptional film-form...Lithium-ion batteries are widely recognized as prime candidates for energy storage devices.Ethylene carbonate(EC)has become a critical component in conventional commercial electrolytes due to its exceptional film-forming properties and high dielectric constant.However,the elevated freezing point,high viscosity,and strong solvation energy of EC significantly hinder the transport rate of Li^(+)and the desolvation process at low temperatures.This leads to substantial capacity loss and even lithium plating on graphite anodes.Herein,we have developed an efficient electrolyte system specifically designed for lowtemperature conditions,which consists of 1.0 M lithium bis(fluorosulfonyl)imide(LiFSI)in isoxazole(IZ)with fluorobenzene(FB)as an uncoordinated solvent and fluoroethylene carbonate(FEC)as a filmforming co-solvent.This system effectively lowers the desolvation energy of Li^(+)through dipole-dipole interactions.The weak solvation capability allows more anions to enter the solvation sheath,promoting the formation of contact ion pairs(CIPs)and aggregates(AGGs)that enhance the transport rate of Li^(+)while maintaining high ionic conductivity across a broad temperature range.Moreover,the formation of inorganic-dominant interfacial phases on the graphite anode,induced by fluoroethylene carbonate,significantly enhances the kinetics of Li^(+)transport.At a low temperature of-20℃,this electrolyte system achieves an impressive reversible capacity of 200.9 mAh g^(-1)in graphite half-cell,which is nearly three times that observed with conventional EC-based electrolytes,demonstrating excellent stability throughout its operation.展开更多
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 goo...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.展开更多
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 com...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.展开更多
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 evaluate...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.展开更多
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...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.展开更多
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.
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 e...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.展开更多
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 s...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.展开更多
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-tr...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.展开更多
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 co...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.展开更多
The chiral phosphoric acid catalyst enables the atroposelective arylation of 5-aminoisoxazoles and quinones by accelerating the kinetics of the enantioselective catalytic reaction, effectively outcompeting and even su...The chiral phosphoric acid catalyst enables the atroposelective arylation of 5-aminoisoxazoles and quinones by accelerating the kinetics of the enantioselective catalytic reaction, effectively outcompeting and even suppressing the uncatalyzed racemic background reaction. In this strategy, a large panel of axially chiral isoxazole-derived amino alcohols was synthesized with generally high yields and excellent enantioselectivities. The method features mild reaction conditions, broad functional group compatibility and good scalability. X-ray crystallography and thermal racemization experiments revealed the important role of six-membered intramolecular O?H···O hydrogen bonding in stabilizing the configurations, which exhibit markedly different racemization barriers in protic and aprotic solvents. Moreover, preliminary mechanistic studies, including nonlinear effects and control experiments were conducted to elucidate the reaction mechanism and activation mode. This approach not only provides an efficient method for constructing pentatomic isoxazole scaffolds, but also expands the family of axially chiral amino alcohols.展开更多
Dynamic communication between hepatocytes and the environment is critical in hepatocellular carcinoma (HCC) development.Clinical immunotherapy against HCC is currently unsatisfactory and needs more systemic considerat...Dynamic communication between hepatocytes and the environment is critical in hepatocellular carcinoma (HCC) development.Clinical immunotherapy against HCC is currently unsatisfactory and needs more systemic considerations, including theidentification of new biomarkers and immune checkpoints. Transmembrane 4 L six family member 5 (TM4SF5) is known to promoteHCC, but it remains unclear how cancerous hepatocytes avoid immune surveillance and whether avoidance can be blocked. Weinvestigated how TM4SF5-mediated hepatic tumorigenesis avoids surveillance by natural killer (NK) cells, which are prevalent in theliver, and whether the avoidance can be blocked by anti-TM4SF5 agents. We used comprehensive structure activity relationshipanalysis to identify TM4SF5-specific isoxazole (TSI)-based small molecules that inhibit TM4SF5-mediated effects. TM4SF5 expressedby hepatocytes reduced NK cell cytotoxicity by downregulating stimulatory ligands/receptors, including signaling lymphocyticactivation molecule family member 7 (SLAMF7). TM4SF5 bound SLAMF7 depending on N-glycosylation and caused intracellulartrafficking of SLAMF7 from the plasma membrane to lysosomes for degradation. TSI treatments in cell lines and animal models ofHCC blocked this binding, intracellular trafficking, and downregulation, resulting in higher levels of stimulatory NK cell ligands. Inmouse xenograft models, TSI treatment abrogated HCC development by increasing the abundance and dispersion of Slamf7-positive cells in liver tissues, recapitulating the phenotype of Tm4sf5-knockout mice and indicating TSI-mediated restoration of NKcell surveillance. These findings suggest that TSIs can inhibit TM4SF5-mediated liver carcinogenesis by increasing NK cellsurveillance.展开更多
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 so...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.展开更多
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 repert...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.展开更多
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 struct...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.展开更多
文摘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.
基金partial financial support from the National Key R&D Program of China(No.2016YFE0132600)Henan Center for Outstanding Overseas Scientists(No.GZS2020001)Key Scientific and Technological Project of Henan Province(No.212102311068)。
文摘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.
基金We thank the National Natural Science Foundation of China(No.20562005)NSF of Jiangxi Province for financial support.
文摘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.
基金the National Natural Science Foundation of China(Nos.22171178,21871174 to B.X.)Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-09-E00008 to B.X.)for financial support+2 种基金The Sailing Program of Science and Technology Commission of Shanghai Municipality(22YF1413200 to M.G.)Young Talents Sailing Project(Shanghai University to M.G.)Shanghai Overseas Leading Talents Project(M.G.)are also appreciated.
文摘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.
文摘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.
基金financial support from the Department of Science and Technology of Jilin Province(20240304104SF,20240304103SF)the Research and Innovation Fund of the Beihua University for the Graduate Student(Major Project 2023012)。
文摘Lithium-ion batteries are widely recognized as prime candidates for energy storage devices.Ethylene carbonate(EC)has become a critical component in conventional commercial electrolytes due to its exceptional film-forming properties and high dielectric constant.However,the elevated freezing point,high viscosity,and strong solvation energy of EC significantly hinder the transport rate of Li^(+)and the desolvation process at low temperatures.This leads to substantial capacity loss and even lithium plating on graphite anodes.Herein,we have developed an efficient electrolyte system specifically designed for lowtemperature conditions,which consists of 1.0 M lithium bis(fluorosulfonyl)imide(LiFSI)in isoxazole(IZ)with fluorobenzene(FB)as an uncoordinated solvent and fluoroethylene carbonate(FEC)as a filmforming co-solvent.This system effectively lowers the desolvation energy of Li^(+)through dipole-dipole interactions.The weak solvation capability allows more anions to enter the solvation sheath,promoting the formation of contact ion pairs(CIPs)and aggregates(AGGs)that enhance the transport rate of Li^(+)while maintaining high ionic conductivity across a broad temperature range.Moreover,the formation of inorganic-dominant interfacial phases on the graphite anode,induced by fluoroethylene carbonate,significantly enhances the kinetics of Li^(+)transport.At a low temperature of-20℃,this electrolyte system achieves an impressive reversible capacity of 200.9 mAh g^(-1)in graphite half-cell,which is nearly three times that observed with conventional EC-based electrolytes,demonstrating excellent stability throughout its operation.
文摘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.
基金the Natural Science Foundation of Xinjiang Science Technology Agency(No.2009211A02) for the support
文摘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.
基金Supported by the National Natural Science Foundation of China(No. 20872069)the National Basic Research Program of China(No.2010CB126106)the Fund of State Key Laboratory of Elemento-Organic Chemistry,China
文摘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.
基金supported by a grant from the National Natural Science Foundation of China.
文摘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.
基金We are grateful to the National Natural Science Foundation of China(20332060)the CAS Academician Foundation of Zhejiang Province.
文摘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.
基金financial assistance received from the Department of Biotechnology,Ministry of Science and Technology,New Delhi (BT/PR26189/GET/119/226/2017)DST-SERB,New Delhi (EMR/2017/000465).
文摘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.
基金supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars of the State Education Ministry, No. (2007)1108Key Program of Tianjin Municipal Health Bureau, No. 09KR04
文摘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.
文摘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.
文摘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.
基金the financial support from the National Natural Science Foundation of China(22201022)Hunan Provincial Natural Science Foundation of China(2024JJ5011).Our gratitude goes out to Dr.Xueying Qiu and Zhi-Wei Li from the Analytical and Testing Center of Changsha University of Science and Technology for their assistance with NMR spectrum analysis and HRMS.
文摘The chiral phosphoric acid catalyst enables the atroposelective arylation of 5-aminoisoxazoles and quinones by accelerating the kinetics of the enantioselective catalytic reaction, effectively outcompeting and even suppressing the uncatalyzed racemic background reaction. In this strategy, a large panel of axially chiral isoxazole-derived amino alcohols was synthesized with generally high yields and excellent enantioselectivities. The method features mild reaction conditions, broad functional group compatibility and good scalability. X-ray crystallography and thermal racemization experiments revealed the important role of six-membered intramolecular O?H···O hydrogen bonding in stabilizing the configurations, which exhibit markedly different racemization barriers in protic and aprotic solvents. Moreover, preliminary mechanistic studies, including nonlinear effects and control experiments were conducted to elucidate the reaction mechanism and activation mode. This approach not only provides an efficient method for constructing pentatomic isoxazole scaffolds, but also expands the family of axially chiral amino alcohols.
基金supported by the National Research Foundation of Korea(NRF)funded by the Korea government(MSIT)(NRF-2022R1C1C2003502)to HSKby Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2020R1A2C3008993 and NRF-2021M3A9D3024752)to J.W.L.Graphical elements used in the figures of this manuscript were created with BioRender.com.
文摘Dynamic communication between hepatocytes and the environment is critical in hepatocellular carcinoma (HCC) development.Clinical immunotherapy against HCC is currently unsatisfactory and needs more systemic considerations, including theidentification of new biomarkers and immune checkpoints. Transmembrane 4 L six family member 5 (TM4SF5) is known to promoteHCC, but it remains unclear how cancerous hepatocytes avoid immune surveillance and whether avoidance can be blocked. Weinvestigated how TM4SF5-mediated hepatic tumorigenesis avoids surveillance by natural killer (NK) cells, which are prevalent in theliver, and whether the avoidance can be blocked by anti-TM4SF5 agents. We used comprehensive structure activity relationshipanalysis to identify TM4SF5-specific isoxazole (TSI)-based small molecules that inhibit TM4SF5-mediated effects. TM4SF5 expressedby hepatocytes reduced NK cell cytotoxicity by downregulating stimulatory ligands/receptors, including signaling lymphocyticactivation molecule family member 7 (SLAMF7). TM4SF5 bound SLAMF7 depending on N-glycosylation and caused intracellulartrafficking of SLAMF7 from the plasma membrane to lysosomes for degradation. TSI treatments in cell lines and animal models ofHCC blocked this binding, intracellular trafficking, and downregulation, resulting in higher levels of stimulatory NK cell ligands. Inmouse xenograft models, TSI treatment abrogated HCC development by increasing the abundance and dispersion of Slamf7-positive cells in liver tissues, recapitulating the phenotype of Tm4sf5-knockout mice and indicating TSI-mediated restoration of NKcell surveillance. These findings suggest that TSIs can inhibit TM4SF5-mediated liver carcinogenesis by increasing NK cellsurveillance.
文摘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.
基金financial support provided by the National Natural Science Foundation of China(NSFC,grant nos.92156025 and 22271212)the National Key Research and Development Program of China(grant nos.2019YFA0905100 and 2021YFF0701700)X.T.thanks the China Postdoctoral Science Foundation(grant no.2022M712350).
文摘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.
基金the National Natural Science Foundation of China(Nos.31801784 and 31572042)Natural Science Foundation of Heilongjiang Province(No.ZD2017002)the Research Science Foundation in Technology Innovation of Harbin(No.2017RAQXJ0172)。
文摘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.
