Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread applicati...Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread application in industry.Herein,an engineered IRED from Streptomyces viridochromogenes was developed through four rounds of directed evolution.The engineered SvIRED displayed a significant increase in specific activity to 136.8 U mg^(-1),the highest reported for an IRED to date.Molecular dynamics simulations elucidated the surge in specific activity during mutations.The best mutant can also catalyse the reductive coupling of aldehyde homologs and primary amines with up to 66.9 U mg^(-1).Additionally,we established an in-situ product adsorption system using resin,which significantly alleviated substrate/product inhibition and enhanced substrate loading to 100 g L^(-1).Under optimal conditions,a wide range of chiral 2-aryl-pyrrolidines were successfully produced at high substrate loadings(50-100 g L^(-1))with enantiomeric excess over 99%.The usefulness of this biocatalytic system was further demonstrated by preparation of pharmaceutically relevant chiral 2-aryl pyrrolidines,particularly the decagram-scale synthesis of the key chiral aticaprant intermediate with 90%isolated yield,>99%ee,and 438 g L^(-1) d^(-1) space-time yield.展开更多
2,3-Dihydro-2-aryl-4（1H）-quinazolinones were prepared in good yields via condensation of o-aminobenzamide with aldehydes promoted by a catalytic amount of Sc（OTf）3 under mild conditions.
10 mol% Cul combined with the DMEDA ligand can efficiently catalyze the N-arylation of 2-arylindoles with aryl iodides and aryl bromides in good to excellent yields. The aryl halides bearing electron-rich or electron-...10 mol% Cul combined with the DMEDA ligand can efficiently catalyze the N-arylation of 2-arylindoles with aryl iodides and aryl bromides in good to excellent yields. The aryl halides bearing electron-rich or electron-deficient functional groups can be well tolerated under this mild reaction conditions.展开更多
Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysi...Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysis. They both showed high activities in NIH mice.展开更多
A series of 2-aryl-5-alkyl-7-methoxylbenzo[b]furan derivatives have been synthesized by utilizing the coupling of methyl 3- methoxy-4hydroxy-5-bromocinnamate with cuprous phenylacetylide as the key step. The structure...A series of 2-aryl-5-alkyl-7-methoxylbenzo[b]furan derivatives have been synthesized by utilizing the coupling of methyl 3- methoxy-4hydroxy-5-bromocinnamate with cuprous phenylacetylide as the key step. The structures of the new compounds were confirmed by 1H NMR, IR and MS. The structure of compound 14 was further confirmed by single crystal X-ray. Compound 17 showed cytotoxic activity against human lung carcinoma A549.展开更多
1, 4-Bis[3-N-propionyl-2-aryl-1, 3, 4-oxadiazoline-5-yl]phenylenes 4 were synthesized by cyclization of corresponding hydrazones 3 with propionic anhydride.
Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines （6-8 and their enantiomers）, the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six- membered cyclic nitro...Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines （6-8 and their enantiomers）, the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six- membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition （IC50 1080 μmol/L） against β-galactosidase from rat intestinal lactases.展开更多
2-Aryl-3H-indol-3-ones (3a-o) have been synthesized via methanol trapping reaction in singlet oxygenation of 2-arylindoles (1a-o), followed by thermal decomposition of the resultant 2-aryl-2-methoxy-3-oxo-2,3-dihydroi...2-Aryl-3H-indol-3-ones (3a-o) have been synthesized via methanol trapping reaction in singlet oxygenation of 2-arylindoles (1a-o), followed by thermal decomposition of the resultant 2-aryl-2-methoxy-3-oxo-2,3-dihydroindoles (2a-o) in good yields.展开更多
A highly selective synthesis of 2-aryl-l-arylmethyl-lH-1,3-benzimidazoles from the reaction of o-phenylene- diamine and aromatic aldehydes in the presence of silica-bonded propyl-S-sulfonic acid （SBSSA） at 80℃ in w...A highly selective synthesis of 2-aryl-l-arylmethyl-lH-1,3-benzimidazoles from the reaction of o-phenylene- diamine and aromatic aldehydes in the presence of silica-bonded propyl-S-sulfonic acid （SBSSA） at 80℃ in water in good to excellent yields was developed.展开更多
In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanic...In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.展开更多
An environmental benign procedure for synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles has been developed by reaction of 2-amino-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with formic acid in PEG-400.The...An environmental benign procedure for synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles has been developed by reaction of 2-amino-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with formic acid in PEG-400.The key advantages of this protocol are the shorter reaction time,higher yields,lower cost,simple workup,and environment-friendly compared to conventional organic solvent reaction.The present method does not involve any hazardous organic solvent or catalyst.展开更多
A new and ancient solid-state reaction using K3Fe(CN)(6)/KOII to oxidize diaryl semicarbazides for preparing azo compounds has been reported. Nine N-aryl-2-phenyl-diazenecarboxamides have been synthesized in excellent...A new and ancient solid-state reaction using K3Fe(CN)(6)/KOII to oxidize diaryl semicarbazides for preparing azo compounds has been reported. Nine N-aryl-2-phenyl-diazenecarboxamides have been synthesized in excellent yields with simple instrument.展开更多
Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2（5H）-ones from the condensation between aldehydes, amines and dialkylacetylendicarboxylates at ambient tem...Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2（5H）-ones from the condensation between aldehydes, amines and dialkylacetylendicarboxylates at ambient temperature in Et OH. In addition, N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates were synthesised using mentioned catalyst at ambient temperature in Et OH from condensation between formaldehyde, amines, and dialkylacetylenedicarboxylates. This methodology has number of advantages such as： use of green and nonhazardous catalyst, clean work up, short reaction times,high yields and no need to column chromatography.展开更多
A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives 8a-f and 9a-f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the ...A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives 8a-f and 9a-f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 8c, 9c and 9e exhibited comparable antimicrobial activity to first line drugs.展开更多
A series of 3-pyridinyl-6-aryl-l, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazoles(PATT) were prepared, the structures were confirmed by IR and H NMR spectra. The results of cyclic 1 voltammetry measurements imply that all ...A series of 3-pyridinyl-6-aryl-l, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazoles(PATT) were prepared, the structures were confirmed by IR and H NMR spectra. The results of cyclic 1 voltammetry measurements imply that all these compounds have a higher electron affinity (EA) than 2-(4-biphenyl)-5-(4-tert-butyl phenyl)-1, 3, 4-oxadiazole (PBD) which implies that PATT could be acting as better electron acceptors than widely used electron transporting material PBD.展开更多
Using a catalytic amount of Nal and a stoichiometric oxidant Oxone-@,a convenient procedure has been developed for the catalytic oxidative 1,2-shift of arylalkenes in CH3CN/H2O at room temperature,which provides the c...Using a catalytic amount of Nal and a stoichiometric oxidant Oxone-@,a convenient procedure has been developed for the catalytic oxidative 1,2-shift of arylalkenes in CH3CN/H2O at room temperature,which provides the corresponding α-aryl ketones in moderate to good yields.In this protocol,sodium iodide is first oxidized into hypoiodous acid,which reacts with arylalkene to afford iodohydrin.Then,the iodohydrin is transformed into the α-aryl ketone via an oxidative 1,2-shift rearrangement.展开更多
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread application in industry.Herein,an engineered IRED from Streptomyces viridochromogenes was developed through four rounds of directed evolution.The engineered SvIRED displayed a significant increase in specific activity to 136.8 U mg^(-1),the highest reported for an IRED to date.Molecular dynamics simulations elucidated the surge in specific activity during mutations.The best mutant can also catalyse the reductive coupling of aldehyde homologs and primary amines with up to 66.9 U mg^(-1).Additionally,we established an in-situ product adsorption system using resin,which significantly alleviated substrate/product inhibition and enhanced substrate loading to 100 g L^(-1).Under optimal conditions,a wide range of chiral 2-aryl-pyrrolidines were successfully produced at high substrate loadings(50-100 g L^(-1))with enantiomeric excess over 99%.The usefulness of this biocatalytic system was further demonstrated by preparation of pharmaceutically relevant chiral 2-aryl pyrrolidines,particularly the decagram-scale synthesis of the key chiral aticaprant intermediate with 90%isolated yield,>99%ee,and 438 g L^(-1) d^(-1) space-time yield.
基金We are grateful to the National Basic Research Program （No. 2003CB114402）；the National Natural Science Foundation of China （Nos. 20476098 and 20676123） ；Wenzhou University Post-graduate Innovation Foundation （No. YCX0515） for financial support.
文摘2,3-Dihydro-2-aryl-4（1H）-quinazolinones were prepared in good yields via condensation of o-aminobenzamide with aldehydes promoted by a catalytic amount of Sc（OTf）3 under mild conditions.
基金supported by the National Natural Science Foundation of China (No.21102036)Plan for Scientific Innovation Talent of Henan University of Technology (No.11CXRC02)startup fund from HAUT (No.2010BS042)
文摘10 mol% Cul combined with the DMEDA ligand can efficiently catalyze the N-arylation of 2-arylindoles with aryl iodides and aryl bromides in good to excellent yields. The aryl halides bearing electron-rich or electron-deficient functional groups can be well tolerated under this mild reaction conditions.
文摘Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysis. They both showed high activities in NIH mice.
文摘A series of 2-aryl-5-alkyl-7-methoxylbenzo[b]furan derivatives have been synthesized by utilizing the coupling of methyl 3- methoxy-4hydroxy-5-bromocinnamate with cuprous phenylacetylide as the key step. The structures of the new compounds were confirmed by 1H NMR, IR and MS. The structure of compound 14 was further confirmed by single crystal X-ray. Compound 17 showed cytotoxic activity against human lung carcinoma A549.
文摘1, 4-Bis[3-N-propionyl-2-aryl-1, 3, 4-oxadiazoline-5-yl]phenylenes 4 were synthesized by cyclization of corresponding hydrazones 3 with propionic anhydride.
基金Financial support from National Basic Research Program of China (Nos. 2012CB822101 and 2011CB808603)the Natural Science Foundation of China (Nos. 21272240 and 21102149)
文摘Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines （6-8 and their enantiomers）, the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six- membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition （IC50 1080 μmol/L） against β-galactosidase from rat intestinal lactases.
基金Project supported by the Coal Industry Universities Science Foundation of China.
文摘2-Aryl-3H-indol-3-ones (3a-o) have been synthesized via methanol trapping reaction in singlet oxygenation of 2-arylindoles (1a-o), followed by thermal decomposition of the resultant 2-aryl-2-methoxy-3-oxo-2,3-dihydroindoles (2a-o) in good yields.
文摘A highly selective synthesis of 2-aryl-l-arylmethyl-lH-1,3-benzimidazoles from the reaction of o-phenylene- diamine and aromatic aldehydes in the presence of silica-bonded propyl-S-sulfonic acid （SBSSA） at 80℃ in water in good to excellent yields was developed.
文摘In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.
基金support from the Natural Science Foundation of Gansu Province(No.3ZS061- A25-019)the Scientific Research fund of Gansu Provincial Education Department(No.0601-25)
文摘An environmental benign procedure for synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles has been developed by reaction of 2-amino-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with formic acid in PEG-400.The key advantages of this protocol are the shorter reaction time,higher yields,lower cost,simple workup,and environment-friendly compared to conventional organic solvent reaction.The present method does not involve any hazardous organic solvent or catalyst.
基金the financial support from the Natural Science Foundation of Technology Commission of Henan Province.
文摘A new and ancient solid-state reaction using K3Fe(CN)(6)/KOII to oxidize diaryl semicarbazides for preparing azo compounds has been reported. Nine N-aryl-2-phenyl-diazenecarboxamides have been synthesized in excellent yields with simple instrument.
基金financial support from the Research Council of the University of Sistan and Baluchestan,Zahedan, Iran
文摘Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2（5H）-ones from the condensation between aldehydes, amines and dialkylacetylendicarboxylates at ambient temperature in Et OH. In addition, N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates were synthesised using mentioned catalyst at ambient temperature in Et OH from condensation between formaldehyde, amines, and dialkylacetylenedicarboxylates. This methodology has number of advantages such as： use of green and nonhazardous catalyst, clean work up, short reaction times,high yields and no need to column chromatography.
文摘A new series of 2-thiophenoxyquinolines based trifluoromethyl substituted N-aryl quinolone derivatives 8a-f and 9a-f have been synthesized via a one-pot multicomponent reaction. In vitro antimicrobial activity of the synthesized compounds was investigated against a representative panel of pathogenic strains. Compounds 8c, 9c and 9e exhibited comparable antimicrobial activity to first line drugs.
文摘A series of 3-pyridinyl-6-aryl-l, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazoles(PATT) were prepared, the structures were confirmed by IR and H NMR spectra. The results of cyclic 1 voltammetry measurements imply that all these compounds have a higher electron affinity (EA) than 2-(4-biphenyl)-5-(4-tert-butyl phenyl)-1, 3, 4-oxadiazole (PBD) which implies that PATT could be acting as better electron acceptors than widely used electron transporting material PBD.
基金Financial support from the National Natural Science Foundation of China(No.21072176) is greatly appreciated
文摘Using a catalytic amount of Nal and a stoichiometric oxidant Oxone-@,a convenient procedure has been developed for the catalytic oxidative 1,2-shift of arylalkenes in CH3CN/H2O at room temperature,which provides the corresponding α-aryl ketones in moderate to good yields.In this protocol,sodium iodide is first oxidized into hypoiodous acid,which reacts with arylalkene to afford iodohydrin.Then,the iodohydrin is transformed into the α-aryl ketone via an oxidative 1,2-shift rearrangement.
