Aim To synthesize naturally occurring (-) methyl2,2-dimethyl-3-hydroxychromanyl-6-formate. Methods Sharpless' asymmetric dihydroxylation wasemployed to construct the 3-hydroxychroman. Results First asymmetric synt...Aim To synthesize naturally occurring (-) methyl2,2-dimethyl-3-hydroxychromanyl-6-formate. Methods Sharpless' asymmetric dihydroxylation wasemployed to construct the 3-hydroxychroman. Results First asymmetric synthesis of (-) methyl 2,2-dimethyl-3-hydroxychromanyl-6-formate (1) was accomplished starting from methyl 4-hydroxy-benzoate(2), and the absolute configuration was established. Conclusion A useful method for constructingchiral 3-hydroxychroman by employing Sharpless' asymmetric dihydroxylation is achieved.展开更多
The synthesis of 3 chloro 2 nitrotoluene using 2,6 dichloroaniline as starting material by diazotization, substitution, condensation, decarboxylic reaction was studied and the best conditions of the synthetic proc...The synthesis of 3 chloro 2 nitrotoluene using 2,6 dichloroaniline as starting material by diazotization, substitution, condensation, decarboxylic reaction was studied and the best conditions of the synthetic procedures were confirmed. Dichloronitrobenzene was obtained in 78.9% yield based on 2,6 dichloroaniline. The reaction of 2,6 dichloronitrobenzene and methyl cyanoacetate with potassium carbonate catalyst in N,N dimethyl formamide gave methyl 2 cyano 2 (3′ chloro 2′ nitrophenyl) acetate in 80.2% yield. The third procedure product 3 chloro 2 nitrophenylacetic acid was obtained by hydrolysis in 82.6% yield. Decarboxylation reaction of 3 chloro 2 nitrophenylacetic acid produced 3 chloro 2 nitrotoluene in 72.9% yield.The structure of products was identified by IR and NMR.展开更多
Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP...Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP51) and the docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of preliminary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Compound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neoformans, Candida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 also had high activities.展开更多
Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibi...Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.展开更多
Environmental concerns have highlighted the need of cleaner technologies. A cleaner, convenient and selective technology has been developed for the preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (...Environmental concerns have highlighted the need of cleaner technologies. A cleaner, convenient and selective technology has been developed for the preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (DPMP) from 2-methyl-benzene-1,3-diol in water as solvent. The isolated yield of DPMP is up to 86% in good selectivity. The product structure was characterized by conventional methods, H-NMR and MS. This technology belongs to the modern concept of 1 environmentally friendly low wastes or non-wastes technology (LWNWT).展开更多
The synthesis of the title compound ([C28H22ClN2]·ClO4) has been synthesized and its structure was determined by X-ray diffraction. The compound belongs to the monoclinic system, space group P21/n with a = 15.113...The synthesis of the title compound ([C28H22ClN2]·ClO4) has been synthesized and its structure was determined by X-ray diffraction. The compound belongs to the monoclinic system, space group P21/n with a = 15.113(5), b = 8.616(3), c = 19.556(7) ?, β = 92.562(7)°, Z = 4, V = 2544(2) ?3, Mr = 521.38, Dc = 1.361 g/cm3, F(000) = 1080, μ = 0.293 mm-1, the final R = 0.0580 and wR = 0.0788 (I > 2σ(I)). The structure was solved by direct methods and refined by full-matrix least-squares techniques. X-ray analysis revealed that there exist four ring planes of 10H-indolium, pyridinium, p-chlorophenyl and indolyl in the molecule, of which the pyridinium ring forms a conjugated system with the p-chlorophenyl plane. According to the molecular structure of the title compound, it is presumed that the synthetic reaction may undergo the processes of C-addition, cyclization and aromatization.展开更多
目的:本研究通过建立胆管癌大鼠模型,以法尼基衍生物X受体(farnesyl X receptor,FXR)为研究对象,初步探讨FXR在胆管癌大鼠胆管肿瘤组织中的表达状况,以期为治疗胆管癌找到新的方法.方法:取Wistar大鼠(■、体质量160g±8g)70只,随机...目的:本研究通过建立胆管癌大鼠模型,以法尼基衍生物X受体(farnesyl X receptor,FXR)为研究对象,初步探讨FXR在胆管癌大鼠胆管肿瘤组织中的表达状况,以期为治疗胆管癌找到新的方法.方法:取Wistar大鼠(■、体质量160g±8g)70只,随机分为2组,每组35只:普通饮食对照组(简称对照组)予以普通饮食、3'-甲基-4-二甲基氨偶氮苯(3'-Me-DAB)饮食实验组(简称实验组)予以含3'-Me-DAB饮食.经过20wk,建立胆管癌大鼠模型,取对照组胆管组织和实验组胆管肿瘤组织:(1)实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)检测胆管组织和胆管肿瘤组织的FXR基因表达的强度;(2)石蜡切片后用免疫组织化学SP法检测胆管组织和胆管肿瘤组织的FXR蛋白表达的强度.结果:(1)qRT-PCR结果显示:FXR/GAPDH比率在对照组胆管组织中为32,在实验组胆管肿瘤组织中为9,两组间的表达有统计学差异;(2)免疫组织化学SP法结果显示,对照组胆管组织FXR表达阳性率为72.6%,实验组胆管肿瘤组织FXR表达阳性率为21.3%,存在统计学意义(P<0.05).结论:实验组大鼠胆管肿瘤组织的FXR基因的表达较对照组胆管组织减少,提示我们在胆管癌的治疗中,FXR基因有成为新治疗靶点的可能.展开更多
基金This research work was financially supported by the National Natural Science Foundation of China(Grant NO.20272020).
文摘Aim To synthesize naturally occurring (-) methyl2,2-dimethyl-3-hydroxychromanyl-6-formate. Methods Sharpless' asymmetric dihydroxylation wasemployed to construct the 3-hydroxychroman. Results First asymmetric synthesis of (-) methyl 2,2-dimethyl-3-hydroxychromanyl-6-formate (1) was accomplished starting from methyl 4-hydroxy-benzoate(2), and the absolute configuration was established. Conclusion A useful method for constructingchiral 3-hydroxychroman by employing Sharpless' asymmetric dihydroxylation is achieved.
文摘The synthesis of 3 chloro 2 nitrotoluene using 2,6 dichloroaniline as starting material by diazotization, substitution, condensation, decarboxylic reaction was studied and the best conditions of the synthetic procedures were confirmed. Dichloronitrobenzene was obtained in 78.9% yield based on 2,6 dichloroaniline. The reaction of 2,6 dichloronitrobenzene and methyl cyanoacetate with potassium carbonate catalyst in N,N dimethyl formamide gave methyl 2 cyano 2 (3′ chloro 2′ nitrophenyl) acetate in 80.2% yield. The third procedure product 3 chloro 2 nitrophenylacetic acid was obtained by hydrolysis in 82.6% yield. Decarboxylation reaction of 3 chloro 2 nitrophenylacetic acid produced 3 chloro 2 nitrotoluene in 72.9% yield.The structure of products was identified by IR and NMR.
文摘Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP51) and the docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of preliminary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Compound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neoformans, Candida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 also had high activities.
基金the Natural Science Foundation of Jiangsu Province(BK20181128)333 Project of Jiangsu Province(BRA2016518)Jiangsu Provincial Medical Youth Talent(QNRC2016626)。
文摘Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.
文摘Environmental concerns have highlighted the need of cleaner technologies. A cleaner, convenient and selective technology has been developed for the preparation of 3-(4,6-dimethoxy-pyrimidin-2-yloxy)-2-methyl-phenol (DPMP) from 2-methyl-benzene-1,3-diol in water as solvent. The isolated yield of DPMP is up to 86% in good selectivity. The product structure was characterized by conventional methods, H-NMR and MS. This technology belongs to the modern concept of 1 environmentally friendly low wastes or non-wastes technology (LWNWT).
文摘The synthesis of the title compound ([C28H22ClN2]·ClO4) has been synthesized and its structure was determined by X-ray diffraction. The compound belongs to the monoclinic system, space group P21/n with a = 15.113(5), b = 8.616(3), c = 19.556(7) ?, β = 92.562(7)°, Z = 4, V = 2544(2) ?3, Mr = 521.38, Dc = 1.361 g/cm3, F(000) = 1080, μ = 0.293 mm-1, the final R = 0.0580 and wR = 0.0788 (I > 2σ(I)). The structure was solved by direct methods and refined by full-matrix least-squares techniques. X-ray analysis revealed that there exist four ring planes of 10H-indolium, pyridinium, p-chlorophenyl and indolyl in the molecule, of which the pyridinium ring forms a conjugated system with the p-chlorophenyl plane. According to the molecular structure of the title compound, it is presumed that the synthetic reaction may undergo the processes of C-addition, cyclization and aromatization.
文摘目的:本研究通过建立胆管癌大鼠模型,以法尼基衍生物X受体(farnesyl X receptor,FXR)为研究对象,初步探讨FXR在胆管癌大鼠胆管肿瘤组织中的表达状况,以期为治疗胆管癌找到新的方法.方法:取Wistar大鼠(■、体质量160g±8g)70只,随机分为2组,每组35只:普通饮食对照组(简称对照组)予以普通饮食、3'-甲基-4-二甲基氨偶氮苯(3'-Me-DAB)饮食实验组(简称实验组)予以含3'-Me-DAB饮食.经过20wk,建立胆管癌大鼠模型,取对照组胆管组织和实验组胆管肿瘤组织:(1)实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)检测胆管组织和胆管肿瘤组织的FXR基因表达的强度;(2)石蜡切片后用免疫组织化学SP法检测胆管组织和胆管肿瘤组织的FXR蛋白表达的强度.结果:(1)qRT-PCR结果显示:FXR/GAPDH比率在对照组胆管组织中为32,在实验组胆管肿瘤组织中为9,两组间的表达有统计学差异;(2)免疫组织化学SP法结果显示,对照组胆管组织FXR表达阳性率为72.6%,实验组胆管肿瘤组织FXR表达阳性率为21.3%,存在统计学意义(P<0.05).结论:实验组大鼠胆管肿瘤组织的FXR基因的表达较对照组胆管组织减少,提示我们在胆管癌的治疗中,FXR基因有成为新治疗靶点的可能.
