Acetophenone oxime and benzaldehyde oxime were converted to oxime ethers in the presence of alkyl halide or methyl sulfate and KOH in aqueous DMSO in 5 to 70 min. The yields of oxime ethers were 70 - 96%.
The enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine is discussed by the density functional theory(DFT)method.The main intermediates and transition states for this reaction are o...The enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine is discussed by the density functional theory(DFT)method.The main intermediates and transition states for this reaction are optimized completely at the B3LYP/6-31g(d)level,and the transition states are verified by vibrational modes.As shown,the chirality-controlled steps for this re-action are the hydride transfer from borane to carbonyl carbon and oxime carbon of keto oxime ether,and the chirality for the reduced products is determined in these two reaction steps.In all examined reaction paths,the first hydride is transferred via a six-membered ring and the second hydride via a five-membered ring or a four-membered ring.展开更多
A pair of E/Z-isomers of 2-phenyl-6,7-dihydrobenzofuran-4（5H）-one O-cyanomethyl oxime,C16H14N2O2,as potential drugs for treating peptic ulcer and other acid-related diseases have been synthesized and characterized b...A pair of E/Z-isomers of 2-phenyl-6,7-dihydrobenzofuran-4（5H）-one O-cyanomethyl oxime,C16H14N2O2,as potential drugs for treating peptic ulcer and other acid-related diseases have been synthesized and characterized by IR,MS and NMR spectra.Meanwhile,the crystal of IIIa was obtained and determined by X-ray single-crystal diffraction.Crystal data： monoclinic system,space group P21 /c,a = 8.423（8）,b = 19.596（16）,c = 8.770（8）,β = 107.750（12）°,V = 1379（2）3,Z = 4,F（000） = 560,Dc = 1.283 g/cm3,μ = 0.086 mm 1,R = 0.0681 and wR = 0.2029 for 14472 independent reflections（Rint = 0.0782） and 2428 observed ones（I 2σ（I））.展开更多
The crystal structure of the title compound （C18H18N4O, Mr = 306.36） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with α = 4.783（0）, b = 13.577（1）, c = 13...The crystal structure of the title compound （C18H18N4O, Mr = 306.36） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with α = 4.783（0）, b = 13.577（1）, c = 13.830（1） A, α = 63.581（2）, β = 88.326（2）, γ = 86.161（2）°, V= 802.5（1） A3, Z= 2, Dc = 1.268 g/cm^3, F（000） = 324, μ（MoKa） = 0.082 mm^-1, the final R = 0.0497 and wR = 0.1199 for 3094 observed reflections （I 〉 2σ（I））. The dihedral angles between the phenyl （C（1）-C（4）-（6）） and triazole, the phenyl （C（13）-C（15）-C（18）） and triazole, and the two phenyl rings are 7.9（1）, 69.9（1） and 67.8（1）°, respectively. Strong C-H…π interaction joins molecules into a chain along the c axis and contributes to the stability of the structure. Preliminary bioassay results show that the title compound possesses excellent and selective fungicidal activity against Colletotrichum gossypii but displays moderate to weak insecticidal activity against aphides.展开更多
Sigma-1 receptor(σ1R)has become a focus point of drug discovery for central nervous system(CNS)diseases.A series of novel 1-phenylethan-1-one O-(2-aminoethyl)oxime derivatives were synthesized.In vitro biological eva...Sigma-1 receptor(σ1R)has become a focus point of drug discovery for central nervous system(CNS)diseases.A series of novel 1-phenylethan-1-one O-(2-aminoethyl)oxime derivatives were synthesized.In vitro biological evaluation led to the identification of 1a,14a,15d and 16d as the most high-affinity(K_(i)<4 nmol/L)and selectiveσ1R agonists.Among these,15d,the most metabolically stable derivative exhibited high selectivity forσ1R in relation toσ_(2)R and 52 other human targets.In addition to low CYP450 inhibition and induction,15d also exhibited high brain permeability and excellent oral bioavailability.Importantly,15d demonstrated effective antipsychotic potency,particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models,both of which are major challenges for schizophrenia treatment.Moreover,15d produced no significant extrapyramidal symptoms,exhibiting superior pharmacological profiles in relation to current antipsychotic drugs.Mechanistically,15d inhibited GSK3βand enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons.Collectively,these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulatingσ1R represents a potential new therapeutic approach for schizophrenia.The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.展开更多
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 sub...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.展开更多
文摘Acetophenone oxime and benzaldehyde oxime were converted to oxime ethers in the presence of alkyl halide or methyl sulfate and KOH in aqueous DMSO in 5 to 70 min. The yields of oxime ethers were 70 - 96%.
基金supported by the Key Project of Science and Technology of the Ministry of Edu-cation of China(Grant No.104263).
文摘The enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine is discussed by the density functional theory(DFT)method.The main intermediates and transition states for this reaction are optimized completely at the B3LYP/6-31g(d)level,and the transition states are verified by vibrational modes.As shown,the chirality-controlled steps for this re-action are the hydride transfer from borane to carbonyl carbon and oxime carbon of keto oxime ether,and the chirality for the reduced products is determined in these two reaction steps.In all examined reaction paths,the first hydride is transferred via a six-membered ring and the second hydride via a five-membered ring or a four-membered ring.
基金Supported by the National Natural Science Foundation of China(Nos.21102084,21272136,31070313)Scientific and Technological Research Project of Hubei Provincial Department of Education(No.Q20111210)Science Foundation of China Three Gorges University(No.KJ2010B001)
文摘A pair of E/Z-isomers of 2-phenyl-6,7-dihydrobenzofuran-4（5H）-one O-cyanomethyl oxime,C16H14N2O2,as potential drugs for treating peptic ulcer and other acid-related diseases have been synthesized and characterized by IR,MS and NMR spectra.Meanwhile,the crystal of IIIa was obtained and determined by X-ray single-crystal diffraction.Crystal data： monoclinic system,space group P21 /c,a = 8.423（8）,b = 19.596（16）,c = 8.770（8）,β = 107.750（12）°,V = 1379（2）3,Z = 4,F（000） = 560,Dc = 1.283 g/cm3,μ = 0.086 mm 1,R = 0.0681 and wR = 0.2029 for 14472 independent reflections（Rint = 0.0782） and 2428 observed ones（I 2σ（I））.
基金Supported by NNSFC (20302002 and 20872046)the SRF for ROCS, SEM (No. [2007] 1108)
文摘The crystal structure of the title compound （C18H18N4O, Mr = 306.36） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with α = 4.783（0）, b = 13.577（1）, c = 13.830（1） A, α = 63.581（2）, β = 88.326（2）, γ = 86.161（2）°, V= 802.5（1） A3, Z= 2, Dc = 1.268 g/cm^3, F（000） = 324, μ（MoKa） = 0.082 mm^-1, the final R = 0.0497 and wR = 0.1199 for 3094 observed reflections （I 〉 2σ（I））. The dihedral angles between the phenyl （C（1）-C（4）-（6）） and triazole, the phenyl （C（13）-C（15）-C（18）） and triazole, and the two phenyl rings are 7.9（1）, 69.9（1） and 67.8（1）°, respectively. Strong C-H…π interaction joins molecules into a chain along the c axis and contributes to the stability of the structure. Preliminary bioassay results show that the title compound possesses excellent and selective fungicidal activity against Colletotrichum gossypii but displays moderate to weak insecticidal activity against aphides.
基金supported by the National Key Research and Development Program of China(2021YFE0206000)National Natural Science Foundation of China(Nos.22177086,81973334,and 22477093)+2 种基金STI2030-Major Projects(No.2021ZD0204004,China)Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutes(No.22KJA350004,China)Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).
文摘Sigma-1 receptor(σ1R)has become a focus point of drug discovery for central nervous system(CNS)diseases.A series of novel 1-phenylethan-1-one O-(2-aminoethyl)oxime derivatives were synthesized.In vitro biological evaluation led to the identification of 1a,14a,15d and 16d as the most high-affinity(K_(i)<4 nmol/L)and selectiveσ1R agonists.Among these,15d,the most metabolically stable derivative exhibited high selectivity forσ1R in relation toσ_(2)R and 52 other human targets.In addition to low CYP450 inhibition and induction,15d also exhibited high brain permeability and excellent oral bioavailability.Importantly,15d demonstrated effective antipsychotic potency,particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models,both of which are major challenges for schizophrenia treatment.Moreover,15d produced no significant extrapyramidal symptoms,exhibiting superior pharmacological profiles in relation to current antipsychotic drugs.Mechanistically,15d inhibited GSK3βand enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons.Collectively,these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulatingσ1R represents a potential new therapeutic approach for schizophrenia.The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.
基金We are grateful to the National Natural Science Foundation of China （21425205）, Ministry of Education of China, Ying Tung Education Foundation （121014） for financial support.
文摘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.
