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2018 Volume 38 Issue 10
2018, 38(10): 2465-2490
doi: 10.6023/cjoc201803002
Abstract:
The functional switch of a C—H activation directing group to a pharmacophore is introduced and analyzed, and the value of the pharmacophore and the application of C—H activation are exemplified. It is concluded that many pharmacophores, such as N-containing heteroaromatic, nitrile, carboxylic acid, amide and sulfonamide groups, are ideal directing groups for C—H activation enabling the subsequent stages of drug synthesis, and showing that there is a correlation between a directing group and a pharmacophore. The late-stage functionalization will greatly simplify and effectively improve the possibility of discovering new drugs and potentially shortening the overall synthesis. The latest breakthroughs of C—H activation and application in the drug discovery process are reviewed as case studies, providing several industrial examples of using a pharmacophore as directing group for drug synthesis. It is believed that this development will promote a more rapid and green drug synthesis.
The functional switch of a C—H activation directing group to a pharmacophore is introduced and analyzed, and the value of the pharmacophore and the application of C—H activation are exemplified. It is concluded that many pharmacophores, such as N-containing heteroaromatic, nitrile, carboxylic acid, amide and sulfonamide groups, are ideal directing groups for C—H activation enabling the subsequent stages of drug synthesis, and showing that there is a correlation between a directing group and a pharmacophore. The late-stage functionalization will greatly simplify and effectively improve the possibility of discovering new drugs and potentially shortening the overall synthesis. The latest breakthroughs of C—H activation and application in the drug discovery process are reviewed as case studies, providing several industrial examples of using a pharmacophore as directing group for drug synthesis. It is believed that this development will promote a more rapid and green drug synthesis.
2018, 38(10): 2491-2500
doi: 10.6023/cjoc201805001
Abstract:
Olefin metathesis is among the most popular synthetic methods over the past two decades. Owing to the good functional group tolerance of ruthenium catalysts, hydrogen bonding has emerged as a powerful controlling element for olefin metathesis recently. Recent studies demonstrated that the hydrogen bonding between ruthenium catalyst and certain types of substrates or additives could significantly improve the rate, chemoselectivity and stereoselectivity of olefin metathesis, while the self-assembly of substrates could be driven by intramolecular or intermolecular hydrogen bonding and result in highly selective reactions. In this review, the development and application of hydrogen bonding-promoted ruthenium-catalyzed olefin metathesis reactions are summarized, and the mechanism insights into these systems are highlighted.
Olefin metathesis is among the most popular synthetic methods over the past two decades. Owing to the good functional group tolerance of ruthenium catalysts, hydrogen bonding has emerged as a powerful controlling element for olefin metathesis recently. Recent studies demonstrated that the hydrogen bonding between ruthenium catalyst and certain types of substrates or additives could significantly improve the rate, chemoselectivity and stereoselectivity of olefin metathesis, while the self-assembly of substrates could be driven by intramolecular or intermolecular hydrogen bonding and result in highly selective reactions. In this review, the development and application of hydrogen bonding-promoted ruthenium-catalyzed olefin metathesis reactions are summarized, and the mechanism insights into these systems are highlighted.
2018, 38(10): 2501-2518
doi: 10.6023/cjoc201805016
Abstract:
In recent years, low-valence iodine-catalyzed oxidative coupling reaction has made rapid progress, providing an effective method for the construction of C—C, C—O, C—N, C—S, C—P and other chemical bonds. Compared with the transition metal-catalyzed oxidation coupling reaction, this protocol is metal-free under mild conditions. It avoids the high cost and toxicity of transition metal catalyst, which meets the requirements of green chemistry. Therefore, iodine catalysis has attracted much attention of the synthetic chemists. The research progress on low-valence iodine-catalyzed oxidative coupling from 2010 to now is summarized, and outlook of this field is also prospected.
In recent years, low-valence iodine-catalyzed oxidative coupling reaction has made rapid progress, providing an effective method for the construction of C—C, C—O, C—N, C—S, C—P and other chemical bonds. Compared with the transition metal-catalyzed oxidation coupling reaction, this protocol is metal-free under mild conditions. It avoids the high cost and toxicity of transition metal catalyst, which meets the requirements of green chemistry. Therefore, iodine catalysis has attracted much attention of the synthetic chemists. The research progress on low-valence iodine-catalyzed oxidative coupling from 2010 to now is summarized, and outlook of this field is also prospected.
2018, 38(10): 2519-2533
doi: 10.6023/cjoc201804017
Abstract:
Carbon monoxide is a readily available and cheap C1 feedstock. Carbonylation, the direct incorporation of carbon monoxide into organic molecules, is a very important and fundamental chemical transformation. In recent years, developing transition-metal-free systems for the carbonylation has attracted highly attention from many researchers. The recent rearch progress of transition-metal-free carbonylations for the synthesis of aldehydes, ketones, esters, amides, acids, anhydrides, acyl chloride, and alcohols is reviewed. And the development and application prospects for transition-metal-free carbonylation are also discussed.
Carbon monoxide is a readily available and cheap C1 feedstock. Carbonylation, the direct incorporation of carbon monoxide into organic molecules, is a very important and fundamental chemical transformation. In recent years, developing transition-metal-free systems for the carbonylation has attracted highly attention from many researchers. The recent rearch progress of transition-metal-free carbonylations for the synthesis of aldehydes, ketones, esters, amides, acids, anhydrides, acyl chloride, and alcohols is reviewed. And the development and application prospects for transition-metal-free carbonylation are also discussed.
2018, 38(10): 2534-2552
doi: 10.6023/cjoc201802022
Abstract:
Ruthenium-catalyzed asymmetric hydrogenation of β-keto esters is one of the most effective methods for the synthesis of chiral β-hydroxy esters. The recent research progress in ruthenium-catalyzed asymmetric hydrogenation of β-keto esters is reviewed. Great attention was paid to the influences of chiral ligands, substrate structure, solvents and additives on the homogeneous asymmetric hydrogenation, as well as the influences of support materials and additives on the heterogeneous asymmetric hydrogenation.
Ruthenium-catalyzed asymmetric hydrogenation of β-keto esters is one of the most effective methods for the synthesis of chiral β-hydroxy esters. The recent research progress in ruthenium-catalyzed asymmetric hydrogenation of β-keto esters is reviewed. Great attention was paid to the influences of chiral ligands, substrate structure, solvents and additives on the homogeneous asymmetric hydrogenation, as well as the influences of support materials and additives on the heterogeneous asymmetric hydrogenation.
2018, 38(10): 2553-2570
doi: 10.6023/cjoc201801035
Abstract:
The wide applications of chiral α-amino acid derivatives in the pharmaceutical and fine chemical industry field has greatly arisen the development of its synthetic methods. So far, asymmetric nucleophilic addition reaction of α-imino ester has been proven to be one of the most effective methods to synthesize chiral α-amino acid derivatives and has been focused by chemists in the field of asymmetric catalysis. The development of such method on the view of reaction types and different kinds of nucleophiles is described. Specifically, allylation reaction, arylation reactions, Mannich reactions, alkenylation reactions, alkynylation reactions and alkylation reactions are introduced, together with the associated reaction mechanisms and recent developments. Additionally, a prospect on this research field is given.
The wide applications of chiral α-amino acid derivatives in the pharmaceutical and fine chemical industry field has greatly arisen the development of its synthetic methods. So far, asymmetric nucleophilic addition reaction of α-imino ester has been proven to be one of the most effective methods to synthesize chiral α-amino acid derivatives and has been focused by chemists in the field of asymmetric catalysis. The development of such method on the view of reaction types and different kinds of nucleophiles is described. Specifically, allylation reaction, arylation reactions, Mannich reactions, alkenylation reactions, alkynylation reactions and alkylation reactions are introduced, together with the associated reaction mechanisms and recent developments. Additionally, a prospect on this research field is given.
2018, 38(10): 2571-2589
doi: 10.6023/cjoc201803045
Abstract:
Recently, transition metal-promoted trifluoromethylation has been developed rapidly. Starting with the types of transition metal that promote the trifluoromethylation reactions, the research progress of trifluoromethylation promoted by silver, iron, palladium, nickel, rhodium and cobalt in recent years is reviewed. Moreover, the possible mechanisms of some parts of reactions are also discussed.
Recently, transition metal-promoted trifluoromethylation has been developed rapidly. Starting with the types of transition metal that promote the trifluoromethylation reactions, the research progress of trifluoromethylation promoted by silver, iron, palladium, nickel, rhodium and cobalt in recent years is reviewed. Moreover, the possible mechanisms of some parts of reactions are also discussed.
2018, 38(10): 2590-2605
doi: 10.6023/cjoc201804001
Abstract:
Carbon-hydrogen bonds are the most extensive and basic chemical bonds existed in organic compounds. Electrochemical functionalization and direct conversion of aromatic C—H bonds is a green, sustainable, and atomically economical transformation pathway, which avoids the pre-functionalization of reactants. The anodic electrooxidation of aromatics allows the formation of C—X (X=C, N, O, S) bonds and the preparation of fused aromatic rings without the use of oxidants. Certain C—H activation reactions with chemoselectivity and regioselectivity can also be achieved by the optimization of electrode materials, electrolytes, and solvents. Vourious reactions focusing on the electrochemical functionalizations of C—H bonds in aromatic compounds are mainly reviewed.
Carbon-hydrogen bonds are the most extensive and basic chemical bonds existed in organic compounds. Electrochemical functionalization and direct conversion of aromatic C—H bonds is a green, sustainable, and atomically economical transformation pathway, which avoids the pre-functionalization of reactants. The anodic electrooxidation of aromatics allows the formation of C—X (X=C, N, O, S) bonds and the preparation of fused aromatic rings without the use of oxidants. Certain C—H activation reactions with chemoselectivity and regioselectivity can also be achieved by the optimization of electrode materials, electrolytes, and solvents. Vourious reactions focusing on the electrochemical functionalizations of C—H bonds in aromatic compounds are mainly reviewed.
2018, 38(10): 2606-2624
doi: 10.6023/cjoc201804009
Abstract:
Porous organic polymer fluorescence materials have the characteristics of high porosity and outstanding fluorescence properties. The function of fluorescence sensing is given when the skeleton has binding sites with specific analytes, such as nitroaromatic explosives (NAEs), metal ions, anions, gases, organic solvents, etc. In this paper, according to the different types of porous organic polymer materials (POPs), namely the amorphous porous organic polymer materials, crystal porous metal organic framework materials (MOFs) containing coordination bond, and crystal covalent organic framework materials (COFs), the new progress of the POPs fluorescence materials in recent years is reviewed. Especially, the design and synthesis based on functional organic molecules, and their fluorescence sensing applications, are introduced in details. In the future, continuing to design new types of fluorescent COFs from the molecular level is a development direction of highly efficient and recyclable fluorescence chemosensors for detecting NAEs, metal ions, anions, etc.
Porous organic polymer fluorescence materials have the characteristics of high porosity and outstanding fluorescence properties. The function of fluorescence sensing is given when the skeleton has binding sites with specific analytes, such as nitroaromatic explosives (NAEs), metal ions, anions, gases, organic solvents, etc. In this paper, according to the different types of porous organic polymer materials (POPs), namely the amorphous porous organic polymer materials, crystal porous metal organic framework materials (MOFs) containing coordination bond, and crystal covalent organic framework materials (COFs), the new progress of the POPs fluorescence materials in recent years is reviewed. Especially, the design and synthesis based on functional organic molecules, and their fluorescence sensing applications, are introduced in details. In the future, continuing to design new types of fluorescent COFs from the molecular level is a development direction of highly efficient and recyclable fluorescence chemosensors for detecting NAEs, metal ions, anions, etc.
2018, 38(10): 2625-2632
doi: 10.6023/cjoc201804025
Abstract:
Opioid drugs are widely used in clinical practice, but they are also notorious for their respiratory depression and addictive side effects. Therefore, tremendous efforts have been paid to the research and development of opioid drugs. Recent progresses in related research fields provide important clues for developing opioid drugs with novel mechanisms. Recent reports on several topics in the study of small molecule opioid drugs are summarized.
Opioid drugs are widely used in clinical practice, but they are also notorious for their respiratory depression and addictive side effects. Therefore, tremendous efforts have been paid to the research and development of opioid drugs. Recent progresses in related research fields provide important clues for developing opioid drugs with novel mechanisms. Recent reports on several topics in the study of small molecule opioid drugs are summarized.
2018, 38(10): 2633-2638
doi: 10.6023/cjoc201803043
Abstract:
Sophora acid sodium was synthesized from matrine, where the lactam unit was saponificated in the presence of aqueous sodium hydroxide. Then, esterfication of the sodium salt with methanol and ethanol produced the corresponding esters in 60%~83% yields. Subsequently, the two pharmacophores, matrine esters and 5-alkoxy-3, 4-dibromo-2 (5H)-furan ketones were combined through a C—N coupling reaction, producing a series of novel matrine derivatives with good yields. The anti-tumor activities of the matrine derivatives against human hepatoma SMMC-7721 cell lines were evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The test results showed that the matrine derivatives can effectly inhibit proliferation of liver cancer cells, and the compound methyl 3-(2-((S)-4-bromo-2-(((1S, 2R, 5S)-2-isopropyl-5-methylcyclohexyl)oxy)-5-oxo-2, 5-dihydrofuran-3-yl)dodecahydropyrido[3, 2, 1-ij][1, 6]naphthyridin-1- yl)propanoate (5a) possessed stronger inhibitory activity against SMMC-7721 cell lines with the IC50 value of 0.0004 μmol/L at 24 h, showing markedly higher inhibitory activity in vitro than cytosine arabinoside (0.4578 μmol/L), vincristine (0.1284 μmol/L) and the parent compound matrine (0.9018 μmol/L).
Sophora acid sodium was synthesized from matrine, where the lactam unit was saponificated in the presence of aqueous sodium hydroxide. Then, esterfication of the sodium salt with methanol and ethanol produced the corresponding esters in 60%~83% yields. Subsequently, the two pharmacophores, matrine esters and 5-alkoxy-3, 4-dibromo-2 (5H)-furan ketones were combined through a C—N coupling reaction, producing a series of novel matrine derivatives with good yields. The anti-tumor activities of the matrine derivatives against human hepatoma SMMC-7721 cell lines were evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The test results showed that the matrine derivatives can effectly inhibit proliferation of liver cancer cells, and the compound methyl 3-(2-((S)-4-bromo-2-(((1S, 2R, 5S)-2-isopropyl-5-methylcyclohexyl)oxy)-5-oxo-2, 5-dihydrofuran-3-yl)dodecahydropyrido[3, 2, 1-ij][1, 6]naphthyridin-1- yl)propanoate (5a) possessed stronger inhibitory activity against SMMC-7721 cell lines with the IC50 value of 0.0004 μmol/L at 24 h, showing markedly higher inhibitory activity in vitro than cytosine arabinoside (0.4578 μmol/L), vincristine (0.1284 μmol/L) and the parent compound matrine (0.9018 μmol/L).
2018, 38(10): 2639-2647
doi: 10.6023/cjoc201805033
Abstract:
An efficient and facile method has been developed for the synthesis of quaternary carbon propargylamines via a one-pot tandem reaction of amines, alkynes, and alkynes under neat condition. Both aliphatic and aromatic terminal alkynes are well compatible with the established reaction, with respect to aliphatic alkynes, AgOTf was used as catalyst for the Markovnikov amine-alkyne-alkyne coupling process. When aromatic alkynes were used as substrates, the reaction was promoted by CuBr2/Zn (OTf)2 co-catalytic system. This tandem reaction exhibits excellent atom efficiency and provides an attractive approach to a diverse range of quaternary carbon propargylamines.
An efficient and facile method has been developed for the synthesis of quaternary carbon propargylamines via a one-pot tandem reaction of amines, alkynes, and alkynes under neat condition. Both aliphatic and aromatic terminal alkynes are well compatible with the established reaction, with respect to aliphatic alkynes, AgOTf was used as catalyst for the Markovnikov amine-alkyne-alkyne coupling process. When aromatic alkynes were used as substrates, the reaction was promoted by CuBr2/Zn (OTf)2 co-catalytic system. This tandem reaction exhibits excellent atom efficiency and provides an attractive approach to a diverse range of quaternary carbon propargylamines.
2018, 38(10): 2666-2672
doi: 10.6023/cjoc201804030
Abstract:
A practical strategy has been described for the preparation of trifluoroethyl-coumarin derivatives using a visible-light-promoted trifluoroethylation reaction of propiolate with trifluoroethyl iodide. These reactions could be carried out at room temperature in good chemical yields with good functional group tolerance.
A practical strategy has been described for the preparation of trifluoroethyl-coumarin derivatives using a visible-light-promoted trifluoroethylation reaction of propiolate with trifluoroethyl iodide. These reactions could be carried out at room temperature in good chemical yields with good functional group tolerance.
2018, 38(10): 2673-2679
doi: 10.6023/cjoc201804016
Abstract:
In order to find more efficient and economical antitumor drugs, a series of novel 2, 4-substituted quinazoline derivatives containing benzimidazole were designed, synthesized and evaluated for their antitumor activities on two human tumor cell lines including human gastric cancer cells (MGC-803), human breast cancer cells (MCF-7) and the normal human gastric epithelial cell line (GES-1) by using thiazolyl blue tetrazolium bromide (MTT) assay in vitro. Among all the tested compounds, some compounds displayed moderate to potent antitumor activities against MGC-803 and MCF-7. When the 4-position of quinazoline was substituted by different aromatic amines, 2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-N-(4-methoxyphen-yl)quinazolin-4-amine (15e) had good anti-tumor activity against MGC-803 with IC50 value of 4.60 μmol·L-1. When the 4-position of quinazoline was replaced by different chalcone, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)quinazo-lin-4-yl)amino)phenyl)-3-(3-nitrophenyl)prop-2-en-1-one (15k) had a strong anti-tumor activity against MGC-803 with IC50 value of 0.97 μmol·L-1, which was significantly better than compound 15e. However, the toxicity of compound 15e was more serious than compound 15k whose toxicity was similar to that of the control drug 5-fluorouracil and gefitinib against GES-1. The result of docking with epidermal growth factor receptor (EGFR) suggested that the binding mode of 15k was better than that of 15e. It is believed that this work would be very useful for developing a new series of EGFR inhibitors.
In order to find more efficient and economical antitumor drugs, a series of novel 2, 4-substituted quinazoline derivatives containing benzimidazole were designed, synthesized and evaluated for their antitumor activities on two human tumor cell lines including human gastric cancer cells (MGC-803), human breast cancer cells (MCF-7) and the normal human gastric epithelial cell line (GES-1) by using thiazolyl blue tetrazolium bromide (MTT) assay in vitro. Among all the tested compounds, some compounds displayed moderate to potent antitumor activities against MGC-803 and MCF-7. When the 4-position of quinazoline was substituted by different aromatic amines, 2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-N-(4-methoxyphen-yl)quinazolin-4-amine (15e) had good anti-tumor activity against MGC-803 with IC50 value of 4.60 μmol·L-1. When the 4-position of quinazoline was replaced by different chalcone, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)quinazo-lin-4-yl)amino)phenyl)-3-(3-nitrophenyl)prop-2-en-1-one (15k) had a strong anti-tumor activity against MGC-803 with IC50 value of 0.97 μmol·L-1, which was significantly better than compound 15e. However, the toxicity of compound 15e was more serious than compound 15k whose toxicity was similar to that of the control drug 5-fluorouracil and gefitinib against GES-1. The result of docking with epidermal growth factor receptor (EGFR) suggested that the binding mode of 15k was better than that of 15e. It is believed that this work would be very useful for developing a new series of EGFR inhibitors.
2018, 38(10): 2713-2719
doi: 10.6023/cjoc201803006
Abstract:
Poly (amido amine)s with diverse topographical structures are promising candidates for gene delivery and drug carriers. A series of poly (amido amine)s (PAAs) with the same repeating units, however, different degree of branching, were successfully prepared by Michael addition polycondensation of N, N-methylenebis (acrylamide) (MBA) and L-cysteine methyl ester hydrochloride (CYS) in a water/dimethyl sulfoxide co-solvent. The obtained disposed cationic PAAs exhibit good DNA condensation capacities.
Poly (amido amine)s with diverse topographical structures are promising candidates for gene delivery and drug carriers. A series of poly (amido amine)s (PAAs) with the same repeating units, however, different degree of branching, were successfully prepared by Michael addition polycondensation of N, N-methylenebis (acrylamide) (MBA) and L-cysteine methyl ester hydrochloride (CYS) in a water/dimethyl sulfoxide co-solvent. The obtained disposed cationic PAAs exhibit good DNA condensation capacities.
2018, 38(10): 2648-2656
doi: 10.6023/cjoc201803041
Abstract:
Two series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized based on the structural features of crizotinib. The cell proliferation inhibition efficacy was estimated against A549, HT29, Hela and Karpas299 cell lines. The results revealed that some target compounds exhibited strong or moderate proliferation inhibition efficacy against tumor cells. N-(3-(2-Aminothiazol-4-yl)phenyl)-3-chlorobenzamide (3d) displayed significant activity against HT29 cancer cell with IC50 value of 4.42 μmol/L, and influence of this compound on the expression of related proteins in the MET signaling pathway in HT29 cells was investigated by Western blot. In addition, the preliminary structure-activity relationship (SAR) of the derivatives was rationalized by docking studies.
Two series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized based on the structural features of crizotinib. The cell proliferation inhibition efficacy was estimated against A549, HT29, Hela and Karpas299 cell lines. The results revealed that some target compounds exhibited strong or moderate proliferation inhibition efficacy against tumor cells. N-(3-(2-Aminothiazol-4-yl)phenyl)-3-chlorobenzamide (3d) displayed significant activity against HT29 cancer cell with IC50 value of 4.42 μmol/L, and influence of this compound on the expression of related proteins in the MET signaling pathway in HT29 cells was investigated by Western blot. In addition, the preliminary structure-activity relationship (SAR) of the derivatives was rationalized by docking studies.
2018, 38(10): 2657-2665
doi: 10.6023/cjoc201803051
Abstract:
A series of novel 1, 3-disubstituted-indol-2-one derivatives containing 1, 3, 4-thiadiazole, thioether and amide moiety were designed and synthesized based on 2, 3-dioxindole (isatin). The inhibition activities of all the target compounds against several cancer cell lines were evaluated via thiazolyl blue tetrazolium bromide (MTT) assay method. The preliminary bioassay results indicated that all of the title compounds exhibited a certain antitumor activity in vitro against human liver cancer cell line (HepG2), human transfer of pancreatic cancer cell line (AsPc-1) and human cervical cancer cell line (Hela). The IC50s values of N-(5-((2-fluorobenzyl)thio)-1, 3, 4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)propanamide (6l) [(11.47±0.01), (2.43±0.05), (1.91±0.06) μmol/L, respectively] and N-(5-((2-methylbenzyl)thio)-1, 3, 4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)-propanamide (6p) [(14.32±0.01), (1.61±0.04), (2.77±0.05) μmol/L, respectively] against HepG2, AsPc-1 and Hela cell lines were lower than that of control gefitinib [(16.41±0.05), (5.19±0.02), (7.89±0.05) μmol/L, respecti-vely].
A series of novel 1, 3-disubstituted-indol-2-one derivatives containing 1, 3, 4-thiadiazole, thioether and amide moiety were designed and synthesized based on 2, 3-dioxindole (isatin). The inhibition activities of all the target compounds against several cancer cell lines were evaluated via thiazolyl blue tetrazolium bromide (MTT) assay method. The preliminary bioassay results indicated that all of the title compounds exhibited a certain antitumor activity in vitro against human liver cancer cell line (HepG2), human transfer of pancreatic cancer cell line (AsPc-1) and human cervical cancer cell line (Hela). The IC50s values of N-(5-((2-fluorobenzyl)thio)-1, 3, 4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)propanamide (6l) [(11.47±0.01), (2.43±0.05), (1.91±0.06) μmol/L, respectively] and N-(5-((2-methylbenzyl)thio)-1, 3, 4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)-propanamide (6p) [(14.32±0.01), (1.61±0.04), (2.77±0.05) μmol/L, respectively] against HepG2, AsPc-1 and Hela cell lines were lower than that of control gefitinib [(16.41±0.05), (5.19±0.02), (7.89±0.05) μmol/L, respecti-vely].
2018, 38(10): 2680-2692
doi: 10.6023/cjoc201805004
Abstract:
Six 2/6-aryl substituted azulene derivatives 1~6 were designed and synthesised. Compounds 1~3 and 4~6 are 2-and 6-substituted derivatives, respectively, where the arly substituents were pentafluorobenzene, benzene and α-thiophene. The UV-Vis spectra, fluorescence spectra, electrochemical properties and proton-responsive properties of 1~6 were studied. To investigate the molecular sturcture, absorption spectra and energy levels of compounds 1~6, density functional theory (DFT) calculations were carried out. In comparison with the UV-Vis spectra of azulene, the absorption of S0→S2 transition of 1~6 showed red-shift (Δλ=6~68 nm). Owing to the strong electron-donating ability of α-thiophene group, remarkable bathochromic shifts of 3 and 6 (Δλ=68 and 48 nm, respectively) were obseved. The fluorescence spectra revealed that 4 (ϕF=0.082) has the highest fluorescence quantum yield of 1~6, while 1-H+ (ϕF=0.359) has the highest fluorescence quantum yield of the protonated compounds 1-H+~6-H+, benefiting from the electron-withdrawing pentafluorophenyl group of 1 and 1-H+. Moreover, the electrochemical analysis and DFT calculations demonstated that the introduction of electron-withdrawing pentafluorophenyl unit in the 2/6-positon of azulene can significantly lower the energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). In comparison with the HOMO/LUMO energy levels of azulene, those of 1 and 4 shift downward with ΔEHOMO/ΔELUMO of －0.23/－0.18 and －0.20/－0.15 eV, respectively. The investigations of physical/chemical properties of 2/6-aryl substituted azulene derivatives will provide valuable insights for developing azulene-based organic functional molecules.
Six 2/6-aryl substituted azulene derivatives 1~6 were designed and synthesised. Compounds 1~3 and 4~6 are 2-and 6-substituted derivatives, respectively, where the arly substituents were pentafluorobenzene, benzene and α-thiophene. The UV-Vis spectra, fluorescence spectra, electrochemical properties and proton-responsive properties of 1~6 were studied. To investigate the molecular sturcture, absorption spectra and energy levels of compounds 1~6, density functional theory (DFT) calculations were carried out. In comparison with the UV-Vis spectra of azulene, the absorption of S0→S2 transition of 1~6 showed red-shift (Δλ=6~68 nm). Owing to the strong electron-donating ability of α-thiophene group, remarkable bathochromic shifts of 3 and 6 (Δλ=68 and 48 nm, respectively) were obseved. The fluorescence spectra revealed that 4 (ϕF=0.082) has the highest fluorescence quantum yield of 1~6, while 1-H+ (ϕF=0.359) has the highest fluorescence quantum yield of the protonated compounds 1-H+~6-H+, benefiting from the electron-withdrawing pentafluorophenyl group of 1 and 1-H+. Moreover, the electrochemical analysis and DFT calculations demonstated that the introduction of electron-withdrawing pentafluorophenyl unit in the 2/6-positon of azulene can significantly lower the energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). In comparison with the HOMO/LUMO energy levels of azulene, those of 1 and 4 shift downward with ΔEHOMO/ΔELUMO of －0.23/－0.18 and －0.20/－0.15 eV, respectively. The investigations of physical/chemical properties of 2/6-aryl substituted azulene derivatives will provide valuable insights for developing azulene-based organic functional molecules.
2018, 38(10): 2693-2699
doi: 10.6023/cjoc201803012
Abstract:
A novel pH probe 7-(4'-(dimethylamino)benzylidene)-isolongifolanone (DB) was designed and synthesized from isolongifolanone and characterized by 1H NMR, 13C NMR, and MS. The recognition properties of the probe towards H+ were investigated by UV-Vis and fluorescence spectroscopy. The results showed that DB exhibited highly selective and sensitive fluorescence response towards H+ ion, and the fluorescence intensity decreased linearly in a relatively low range of acidic pH. In addition, the recognition ability of DB towards H+ was not affected by various metal ions. The fluorescence intensity of DB had a linear relationship in the acidic pH range of 1.0~3.5, I=174.134pH－47.836, R=0.9936. DB was also sensitive to change in surrounding trifluoroacetic acid (TFA) vapor. Moreover, the pH probe was successfully applied to imaging extreme acidity in HeLa cells.
A novel pH probe 7-(4'-(dimethylamino)benzylidene)-isolongifolanone (DB) was designed and synthesized from isolongifolanone and characterized by 1H NMR, 13C NMR, and MS. The recognition properties of the probe towards H+ were investigated by UV-Vis and fluorescence spectroscopy. The results showed that DB exhibited highly selective and sensitive fluorescence response towards H+ ion, and the fluorescence intensity decreased linearly in a relatively low range of acidic pH. In addition, the recognition ability of DB towards H+ was not affected by various metal ions. The fluorescence intensity of DB had a linear relationship in the acidic pH range of 1.0~3.5, I=174.134pH－47.836, R=0.9936. DB was also sensitive to change in surrounding trifluoroacetic acid (TFA) vapor. Moreover, the pH probe was successfully applied to imaging extreme acidity in HeLa cells.
2018, 38(10): 2700-2705
doi: 10.6023/cjoc201803029
Abstract:
In recent years, designing and synthesizing fluorescent nanoprobes with good biocompatibility, stable optical properties and low cytotoxicity are research hotspots in the biomedical field. The novel tetraphenylethene-based fluorescent probe (TPE-Rho) was synthesized by reaction of 1, 1, 2-triphenyl-2-(4-formylphenyl)ethene with 2-(4-oxo-3-phenyl-1, 3-thia-zol-2-ylidene)malononitrile. After the aggregation-induced emission (AIE) characteristics of TPE-Rho were investigated, TPE-Rho dots with uniform particle size distribution were obtained through a modified nanoprecipitation method by using Pluronic F-127 (amphiphilic surfactant) as the encapsulation. TPE-Rho dots have excellent optical property such as strong yellow fluorescence, good stability and long Stokes shift (ca. 200 nm), and have little effect on cell growth activity. Then, TPE-Rho dots were utilized to stain live SK-Hep1 cells and LoVo cells, the staining region and fluorescent intensity were analyzed. The experimental results show that TPE-Rho dots have no significant effect on cell viability, and can stain live cells and selectively act on the cytoplasm. Thus, it can be confirmed that TPE-Rho dots has good biocompatibility, low cytotoxicity, high cell membrane permeability, and good stability, therefore it can be used as a viable cell staining agent.
In recent years, designing and synthesizing fluorescent nanoprobes with good biocompatibility, stable optical properties and low cytotoxicity are research hotspots in the biomedical field. The novel tetraphenylethene-based fluorescent probe (TPE-Rho) was synthesized by reaction of 1, 1, 2-triphenyl-2-(4-formylphenyl)ethene with 2-(4-oxo-3-phenyl-1, 3-thia-zol-2-ylidene)malononitrile. After the aggregation-induced emission (AIE) characteristics of TPE-Rho were investigated, TPE-Rho dots with uniform particle size distribution were obtained through a modified nanoprecipitation method by using Pluronic F-127 (amphiphilic surfactant) as the encapsulation. TPE-Rho dots have excellent optical property such as strong yellow fluorescence, good stability and long Stokes shift (ca. 200 nm), and have little effect on cell growth activity. Then, TPE-Rho dots were utilized to stain live SK-Hep1 cells and LoVo cells, the staining region and fluorescent intensity were analyzed. The experimental results show that TPE-Rho dots have no significant effect on cell viability, and can stain live cells and selectively act on the cytoplasm. Thus, it can be confirmed that TPE-Rho dots has good biocompatibility, low cytotoxicity, high cell membrane permeability, and good stability, therefore it can be used as a viable cell staining agent.
2018, 38(10): 2706-2712
doi: 10.6023/cjoc201803050
Abstract:
Lung cancer threats human health. The poly (lactic-co-glycolic acid)/polyethylene glycol (PLGA-PEG) was synthesized by the coupling method and aptamer S6 was synthesized by the nucleic acid solid-phase phosphorimide method. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide salt was obtained. Acid-mediated (EDC) and N-hydroxysuccinimide (NHS) mediators have resulted in a biotargeting nanocarrier material PLGA-PEG-S6-CY3. PLGA-PEG-S6-CY3/CAP1-siRNA nanoparticles were constructed by carrying the small interfering RNA (CAP1-siRNA) targeting the adenylate cyclase-associated protein 1 through the carrier material, and the sustained release of the CAP1-siRNA was achieved to achieve targeting inhibition of metastasis of non-small cell lung cancer A549 cells. The molecular structures of S6 and PLGA-PEG were characterized by nuclear magnetic resonance spectroscopy and their targeting properties were verified. The binding and release of PLGA-PEG nanoparticles and CAP1-siRNA were detected. Furthermore, the effect of the complex on inhibiting the invasiveness of tumor cells was further investigated. The results showed that the PLGA-PEG molecule prepared by the coupling method was used as the carrier, and the aptamer S6 was synthesized and used to modify PLGA-PEG. The obtained PLGA-PEG nanocomposite has the ability of targeting and carrying siRNA, and can be used in vitro. It can also down-regulate the expression of CAP1 in lung cancer A549 cells and reduce its invasiveness.
Lung cancer threats human health. The poly (lactic-co-glycolic acid)/polyethylene glycol (PLGA-PEG) was synthesized by the coupling method and aptamer S6 was synthesized by the nucleic acid solid-phase phosphorimide method. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide salt was obtained. Acid-mediated (EDC) and N-hydroxysuccinimide (NHS) mediators have resulted in a biotargeting nanocarrier material PLGA-PEG-S6-CY3. PLGA-PEG-S6-CY3/CAP1-siRNA nanoparticles were constructed by carrying the small interfering RNA (CAP1-siRNA) targeting the adenylate cyclase-associated protein 1 through the carrier material, and the sustained release of the CAP1-siRNA was achieved to achieve targeting inhibition of metastasis of non-small cell lung cancer A549 cells. The molecular structures of S6 and PLGA-PEG were characterized by nuclear magnetic resonance spectroscopy and their targeting properties were verified. The binding and release of PLGA-PEG nanoparticles and CAP1-siRNA were detected. Furthermore, the effect of the complex on inhibiting the invasiveness of tumor cells was further investigated. The results showed that the PLGA-PEG molecule prepared by the coupling method was used as the carrier, and the aptamer S6 was synthesized and used to modify PLGA-PEG. The obtained PLGA-PEG nanocomposite has the ability of targeting and carrying siRNA, and can be used in vitro. It can also down-regulate the expression of CAP1 in lung cancer A549 cells and reduce its invasiveness.
2018, 38(10): 2720-2730
doi: 10.6023/cjoc201803048
Abstract:
Cdc25B has become the important target for curing cancer owing to its over expression in kinds of cancers. Compounds containing phenanthroline moiety have become research objectives on the DNA fluorescence probes or the new curing agents for their excellent fluorescence property and bioactivities. Twelve novel 1, 2, 4-triazine scheleton phenanthroling derivatives ARTP1~ARTP12 were first designed and synthesized, the structures of ARTP1~ARTP12 were characterized successfully by means of IR and NMR. The inhibitory activities of ARTP1~ARTP12 against Cdc25B were evaluated. The results show that nine target molecules exhibit excellent inhibitories, four molecules behave better activities than the contrast reference Na3VO4 indicating that they may be used as Cdc25B inhibitors. Meanwhile, three novel complexes Co-ARTP-5, Co-ARTP-6 and Co-ARTP-10 were first afforded by the reaction of the excellent inhibitory active compounds ARTP5, ARTP6 and ARTP10 with Co3+ respectively. The structures of the three complexes were confirmed through IR, UV-Vis, 1H NMR and fluorescence spectra. The interaction modes between the complexes and CT-DNA were explored. As a result, the excitation peaks of the complexes show a red shift and the complexes interact with CT-DNA through the insert mode. The binding constants Kb are (2.12±0.20)×105, (3.29±0.20)×105and (1.50±0.20)×105 L·mol-1, respectively, and it occurs strong fluorescene quenching. The complexes are expected to be the DNA fluorescence probes.
Cdc25B has become the important target for curing cancer owing to its over expression in kinds of cancers. Compounds containing phenanthroline moiety have become research objectives on the DNA fluorescence probes or the new curing agents for their excellent fluorescence property and bioactivities. Twelve novel 1, 2, 4-triazine scheleton phenanthroling derivatives ARTP1~ARTP12 were first designed and synthesized, the structures of ARTP1~ARTP12 were characterized successfully by means of IR and NMR. The inhibitory activities of ARTP1~ARTP12 against Cdc25B were evaluated. The results show that nine target molecules exhibit excellent inhibitories, four molecules behave better activities than the contrast reference Na3VO4 indicating that they may be used as Cdc25B inhibitors. Meanwhile, three novel complexes Co-ARTP-5, Co-ARTP-6 and Co-ARTP-10 were first afforded by the reaction of the excellent inhibitory active compounds ARTP5, ARTP6 and ARTP10 with Co3+ respectively. The structures of the three complexes were confirmed through IR, UV-Vis, 1H NMR and fluorescence spectra. The interaction modes between the complexes and CT-DNA were explored. As a result, the excitation peaks of the complexes show a red shift and the complexes interact with CT-DNA through the insert mode. The binding constants Kb are (2.12±0.20)×105, (3.29±0.20)×105and (1.50±0.20)×105 L·mol-1, respectively, and it occurs strong fluorescene quenching. The complexes are expected to be the DNA fluorescence probes.
2018, 38(10): 2731-2735
doi: 10.6023/cjoc201804029
Abstract:
By introducing N, N-dimethylformamido into 1, 5-benzothiazepine, 6 compounds of 2-substituted-phenyl-3-(N, N-dimethylformamido)-4-methyl-1, 5-benzothiazepine 3a~3f were designed and synthesized, Studies on the synthesis conditions of 3a~3f revealed that 3a~3f were dynamic control products. 3a~3f had obvious inhibitory effect on fungi and bacteria especially for Cryptococcus neoformans and Escherichia coli.
By introducing N, N-dimethylformamido into 1, 5-benzothiazepine, 6 compounds of 2-substituted-phenyl-3-(N, N-dimethylformamido)-4-methyl-1, 5-benzothiazepine 3a~3f were designed and synthesized, Studies on the synthesis conditions of 3a~3f revealed that 3a~3f were dynamic control products. 3a~3f had obvious inhibitory effect on fungi and bacteria especially for Cryptococcus neoformans and Escherichia coli.
Preparation and Properties of Supramolecular Organogel Based on Iodine-Functionalized Pillar[5]arene
2018, 38(10): 2741-2746
doi: 10.6023/cjoc201805003
Abstract:
Pillararenes, a new kind of macrocyclic aromatic compounds, are closely attracted because it was used to construct supramolecular gels. In this paper, an iodine-functionalized pillar[5]arene was designed and synthesized. This pillar[5]arene can form a stable supramolecular organogel in cyclohexanol, and phase transition temperature is approximately 96 ℃. The formation process of the organogel was characterized by concentration dependent 1H NMR spectrum, 2D NOESY experiment, X-ray diffraction (XRD) powder diffraction and scanning electron microscope. The experiment results showed that a sheet-like structure was formed in self-assembly process of iodine-functionalized pillar[5]arene. Meanwhile, the fluorescent recognition properties of organogel were studied. With the addition of 0.5 equiv. of various metal ions (Fe3+, Ag+, Ca2+, Co2+, Ni2+, Cd2+, Pb2+, Zn2+, Cu2+, Mg2+ and Hg2+) onto the organogel, Hg2+ and Ag+ can cause blue fluorescence quenching of the organogel after 10 min. Therefore, this gel can be used for fluorescent detection of Hg2+ and Ag+.
Pillararenes, a new kind of macrocyclic aromatic compounds, are closely attracted because it was used to construct supramolecular gels. In this paper, an iodine-functionalized pillar[5]arene was designed and synthesized. This pillar[5]arene can form a stable supramolecular organogel in cyclohexanol, and phase transition temperature is approximately 96 ℃. The formation process of the organogel was characterized by concentration dependent 1H NMR spectrum, 2D NOESY experiment, X-ray diffraction (XRD) powder diffraction and scanning electron microscope. The experiment results showed that a sheet-like structure was formed in self-assembly process of iodine-functionalized pillar[5]arene. Meanwhile, the fluorescent recognition properties of organogel were studied. With the addition of 0.5 equiv. of various metal ions (Fe3+, Ag+, Ca2+, Co2+, Ni2+, Cd2+, Pb2+, Zn2+, Cu2+, Mg2+ and Hg2+) onto the organogel, Hg2+ and Ag+ can cause blue fluorescence quenching of the organogel after 10 min. Therefore, this gel can be used for fluorescent detection of Hg2+ and Ag+.
2018, 38(10): 2747-2753
doi: 10.6023/cjoc201804019
Abstract:
In order to study the multi-bioactivity of sulfonylurea derivatives, fifteen novel 2-cyano-6-chlorobenzenesul-fonylureas were designed and synthesized according to pharmacophore-combination and bioisosterism strategy, based on the chlorsulfuron and tritosulfuron structure frameworks. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. The preliminary bioactivity test indicated that some of the title compounds had excellent in vitro antibacterial activity and insecticidal activity. For example, at the concentration of 50 mg·L-1, the antifungal activities of 5c, 5f and 5g against Physalospora piricola were 80.3%, 80.3% and 83.6% respectively. 5j exhibted 50% larvicidal activity against Mythimna separate Walker at the dosage of 50 mg·L-1. At the concentration of 0.1 mg·L-1, 5a and 5b showed 100% and 50% insecticidal activity against Culex pipiens pallens, respectively better than that of the control flubendiamide (20%). At an even low concentration of 0.01 mg·L-1, 5a had 70% larvicidal activity, and the LC50 value was 0.0023 mg·L-1.
In order to study the multi-bioactivity of sulfonylurea derivatives, fifteen novel 2-cyano-6-chlorobenzenesul-fonylureas were designed and synthesized according to pharmacophore-combination and bioisosterism strategy, based on the chlorsulfuron and tritosulfuron structure frameworks. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. The preliminary bioactivity test indicated that some of the title compounds had excellent in vitro antibacterial activity and insecticidal activity. For example, at the concentration of 50 mg·L-1, the antifungal activities of 5c, 5f and 5g against Physalospora piricola were 80.3%, 80.3% and 83.6% respectively. 5j exhibted 50% larvicidal activity against Mythimna separate Walker at the dosage of 50 mg·L-1. At the concentration of 0.1 mg·L-1, 5a and 5b showed 100% and 50% insecticidal activity against Culex pipiens pallens, respectively better than that of the control flubendiamide (20%). At an even low concentration of 0.01 mg·L-1, 5a had 70% larvicidal activity, and the LC50 value was 0.0023 mg·L-1.
2018, 38(10): 2754-2760
doi: 10.6023/cjoc201804011
Abstract:
A functionalized porous organic polymer POP-BINOL has been prepared and characterized by various techniques including carbon-13 cross-polarization magic-angle spinning nuclear magnetic resonance (13C CP/MAS NMR), fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (pXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption and thermogravimetric analysis (TG). After being treated with Ti (OiPr)4, the composite material could be used as highly effective and reusable heterogeneous catalyst for asymmetric diethylzinc addition to aldehydes with medium and upper ee value.
A functionalized porous organic polymer POP-BINOL has been prepared and characterized by various techniques including carbon-13 cross-polarization magic-angle spinning nuclear magnetic resonance (13C CP/MAS NMR), fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (pXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption and thermogravimetric analysis (TG). After being treated with Ti (OiPr)4, the composite material could be used as highly effective and reusable heterogeneous catalyst for asymmetric diethylzinc addition to aldehydes with medium and upper ee value.
2018, 38(10): 2761-2766
doi: 10.6023/cjoc201803007
Abstract:
Using choline chloride as cheap and safe accelerator was efficient to promote the Yonemitsu type condensation of indole, benzaldehyde, and malononitrile. More importantly, introducing right amount of water in reaction system was crucial to get desired 3-substituted indoles in good to excellent yields. Due to the catalyst has excellent solubility in aqueous ethanol, the final concoction was easy to separate. Many desired products could be obtained after filtration and washed with cold aqueous ethanol without further purification. Catalyst could further reuse for five more reaction cycles with negligible loss in activity.
Using choline chloride as cheap and safe accelerator was efficient to promote the Yonemitsu type condensation of indole, benzaldehyde, and malononitrile. More importantly, introducing right amount of water in reaction system was crucial to get desired 3-substituted indoles in good to excellent yields. Due to the catalyst has excellent solubility in aqueous ethanol, the final concoction was easy to separate. Many desired products could be obtained after filtration and washed with cold aqueous ethanol without further purification. Catalyst could further reuse for five more reaction cycles with negligible loss in activity.
2018, 38(10): 2767-2774
doi: 10.6023/cjoc201804024
Abstract:
The diversity-orientied synthesis strategy was utilized to diversely derive from the carbonyl of 3-acetyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one, a series of novel 3-acetyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one derivatives were synthesized. The preliminary in vivo and in vitro bioassay results showed that some compounds exhibited excellent fungicidal activity against phytopathagens, such as 3-allyloxyethyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one (7) had 100% control rates against Pseudoperonospora cubensis and Puccinia polysora at the concentration of 400 μg/mL.
The diversity-orientied synthesis strategy was utilized to diversely derive from the carbonyl of 3-acetyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one, a series of novel 3-acetyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one derivatives were synthesized. The preliminary in vivo and in vitro bioassay results showed that some compounds exhibited excellent fungicidal activity against phytopathagens, such as 3-allyloxyethyl-4-phenyl-1-oxaspiro[4, 5]dec-3-en-2-one (7) had 100% control rates against Pseudoperonospora cubensis and Puccinia polysora at the concentration of 400 μg/mL.
2018, 38(10): 2775-2779
doi: 10.6023/cjoc201803011
Abstract:
A novel method to quantify β-glucosidase activity was developed by coupling the cleavage of 2-O-(β-glucopyra-nosyl)ascorbic acid with the reduction of Cu (Ⅱ). The in situ generated Cu (Ⅰ) catalyzed the cycloaddition between weakly fluorescent coumarin and benzyl azide to yield a highly fluorescent triazole product. The fluorescence intensity was dependently enhanced on the increase of the activity of β-glucosidase and a linear relationship was found between 1~40 U/L. This cascade allows detection of β-glucosidase with a limit of detection of 0.456 U/L.
A novel method to quantify β-glucosidase activity was developed by coupling the cleavage of 2-O-(β-glucopyra-nosyl)ascorbic acid with the reduction of Cu (Ⅱ). The in situ generated Cu (Ⅰ) catalyzed the cycloaddition between weakly fluorescent coumarin and benzyl azide to yield a highly fluorescent triazole product. The fluorescence intensity was dependently enhanced on the increase of the activity of β-glucosidase and a linear relationship was found between 1~40 U/L. This cascade allows detection of β-glucosidase with a limit of detection of 0.456 U/L.
2018, 38(10): 2784-2790
doi: 10.6023/cjoc201801040
Abstract:
A series of unreported thiouracil derivatives 7 containing a benzothiazole moiety were synthesized by the reaction of 4-oxo-6-phenyl-2-thioxo-1, 2, 3, 4-tetrahydro-pyrimidine-5-carbonitrile (6) with N-(benzo[d]thiazol-2-yl)-4-(chloromethyl)-benzamide (5), which was prepared from the amidation of 2-aminobenzothiazole and 4-(chloromethyl)benzoyl chloride. The newly synthesized compounds 7 were characterized by IR, MS, NMR, and element analysis. All the compounds were evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis. The results of the 24-hour antibacterial test showed that some compounds had good inhibitory activities against the three tested strains.
A series of unreported thiouracil derivatives 7 containing a benzothiazole moiety were synthesized by the reaction of 4-oxo-6-phenyl-2-thioxo-1, 2, 3, 4-tetrahydro-pyrimidine-5-carbonitrile (6) with N-(benzo[d]thiazol-2-yl)-4-(chloromethyl)-benzamide (5), which was prepared from the amidation of 2-aminobenzothiazole and 4-(chloromethyl)benzoyl chloride. The newly synthesized compounds 7 were characterized by IR, MS, NMR, and element analysis. All the compounds were evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis. The results of the 24-hour antibacterial test showed that some compounds had good inhibitory activities against the three tested strains.
2018, 38(10): 2798-2804
doi: 10.6023/cjoc201803017
Abstract:
The mangrove fungus Penicillium camemberti OUCMDZ-1492 produced a new class of compounds under the oligotrophic condition, which were different from those under the eutrophic condition. Bioassay-guided isolation and chiral resolution for the racemic mixture resulted in the harvest of five α-pyronoids. Their structures were ideinfied as (R, E)-5-(3-hydroxybut-1-en-1-yl)-4-methoxy-6-methyl-2H-pyran-2-one (1), pyrenocine A (2), (R)-pyrenocine B (3), (R)-(－)-pyrenocine E (4) and (S)-(+)-pyrenocine E (5). Their structures, including absolute configurations, were elucidated on the basis of spectral analysis, electronic circular dichroism (ECD) spectra, quantum chemical calculation, and chiral separation. New compound 1 was named as pyrenocine P, and the absolute configurations of compounds 3~5 were determined for the first time. Compounds 2 and 3 showed potent quorum sensing inhibitory activity in Chromobacterium violaceum CV026 with the minimal inhibitory concentrations of 0.16 and 1.0 mg·mL-1, respectively. The minimum inhibitory concentration (MIC) value of (Z)-4-bromo-5-(bromomethylene)-furan-2 (5H)-one (C-30), a positive control, was 0.08 mg·mL-1.
The mangrove fungus Penicillium camemberti OUCMDZ-1492 produced a new class of compounds under the oligotrophic condition, which were different from those under the eutrophic condition. Bioassay-guided isolation and chiral resolution for the racemic mixture resulted in the harvest of five α-pyronoids. Their structures were ideinfied as (R, E)-5-(3-hydroxybut-1-en-1-yl)-4-methoxy-6-methyl-2H-pyran-2-one (1), pyrenocine A (2), (R)-pyrenocine B (3), (R)-(－)-pyrenocine E (4) and (S)-(+)-pyrenocine E (5). Their structures, including absolute configurations, were elucidated on the basis of spectral analysis, electronic circular dichroism (ECD) spectra, quantum chemical calculation, and chiral separation. New compound 1 was named as pyrenocine P, and the absolute configurations of compounds 3~5 were determined for the first time. Compounds 2 and 3 showed potent quorum sensing inhibitory activity in Chromobacterium violaceum CV026 with the minimal inhibitory concentrations of 0.16 and 1.0 mg·mL-1, respectively. The minimum inhibitory concentration (MIC) value of (Z)-4-bromo-5-(bromomethylene)-furan-2 (5H)-one (C-30), a positive control, was 0.08 mg·mL-1.
2018, 38(10): 2736-2740
doi: 10.6023/cjoc201805044
Abstract:
It was found that, copper as a cheap metal, could well catalyze the dehydration reaction of aldoximes to organonitriles in nitrile solvent by using MnO2 as the co-catalyst and PPh3 as the ligand. In contrast, instead of organonitriles, the Cu-catalyzed reactions of the aldoximes in water led to amides, which were the products of the Beckmann rearrangements. These interesting selectivity-switchable reactions afford easy accesses to the related useful organic compounds and may be of both academic and practical values.
It was found that, copper as a cheap metal, could well catalyze the dehydration reaction of aldoximes to organonitriles in nitrile solvent by using MnO2 as the co-catalyst and PPh3 as the ligand. In contrast, instead of organonitriles, the Cu-catalyzed reactions of the aldoximes in water led to amides, which were the products of the Beckmann rearrangements. These interesting selectivity-switchable reactions afford easy accesses to the related useful organic compounds and may be of both academic and practical values.
2018, 38(10): 2780-2783
doi: 10.6023/cjoc201802018
Abstract:
A green and very mild method for the oxidation of benzyl alcohols to aromatic aldehydes with excellent conversions has been developed. The reaction could be carried out directly in air at room temperature and was catalyzed by bis (8-quinolinolato) copper (Ⅱ) with 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO) as co-catalysts. The methodology provided a practical approach for the synthesis of aromatic aldehydes, which has the advantages of environment-friendly, simple workup and high yields.
A green and very mild method for the oxidation of benzyl alcohols to aromatic aldehydes with excellent conversions has been developed. The reaction could be carried out directly in air at room temperature and was catalyzed by bis (8-quinolinolato) copper (Ⅱ) with 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO) as co-catalysts. The methodology provided a practical approach for the synthesis of aromatic aldehydes, which has the advantages of environment-friendly, simple workup and high yields.
2018, 38(10): 2791-2797
doi: 10.6023/cjoc201803016
Abstract:
The direct functionalization of the C (sp3)—H bond adjacent to the phosphonate group for the preparation of vinyl phosphonates was rarely developed. Herein, a simple and efficient tetrabutylammonium iodide catalyzed protocol for the preparation of vinyl phosphonates from benzylic phosphonates and paraformaldehyde is achieved under mild conditions in air. Moderate to high yields can be obtained for a broad scope of substrates.
The direct functionalization of the C (sp3)—H bond adjacent to the phosphonate group for the preparation of vinyl phosphonates was rarely developed. Herein, a simple and efficient tetrabutylammonium iodide catalyzed protocol for the preparation of vinyl phosphonates from benzylic phosphonates and paraformaldehyde is achieved under mild conditions in air. Moderate to high yields can be obtained for a broad scope of substrates.
