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2018 Volume 38 Issue 12
2018, 38(12): 3143-3154
doi: 10.6023/cjoc201804006
Abstract:
Fluofullerenes have attracted extensive attention due to their unique structures. The structures and the electronic properties of various fluofullerenes are mainly introduced, and then their applications are summarized in the field of precursors of functional fullerene derivatives, surface doping of diamond, dilicon, and graphene, and bulk p-doping of organic semiconductors in electronic devices. Furthermore, this review introduces the progress of new research on their application in other field, and gives the outlook for research trend and prospect of fluofullerenes materials.
Fluofullerenes have attracted extensive attention due to their unique structures. The structures and the electronic properties of various fluofullerenes are mainly introduced, and then their applications are summarized in the field of precursors of functional fullerene derivatives, surface doping of diamond, dilicon, and graphene, and bulk p-doping of organic semiconductors in electronic devices. Furthermore, this review introduces the progress of new research on their application in other field, and gives the outlook for research trend and prospect of fluofullerenes materials.
2018, 38(12): 3155-3164
doi: 10.6023/cjoc201806009
Abstract:
Recently, the photo-induced radical reactions have emerged as a hot research topic in the field of organic synthetic chemistry. Among these, the radical acylation reaction via photocatalyst is one of the most effecient strategy to prepare ketones under mild conditions. The recent progress on the photo-induced reactions of acyl radical, various acyl radical sources and its application in the organic synthesis is summaried.
Recently, the photo-induced radical reactions have emerged as a hot research topic in the field of organic synthetic chemistry. Among these, the radical acylation reaction via photocatalyst is one of the most effecient strategy to prepare ketones under mild conditions. The recent progress on the photo-induced reactions of acyl radical, various acyl radical sources and its application in the organic synthesis is summaried.
2018, 38(12): 3165-3175
doi: 10.6023/cjoc201806043
Abstract:
The endoplasmic reticulum, a subcellular organelle, plays an important role in the life activities of mammalian cells. Therefore, visualizing the endoplasmic reticulum, and further examining its active substances, microenvironments and physiological processes have important guiding value for the diagnosis and treatment of related diseases. In recent years, the design and synthesis of endoplasmic reticulum-targetable fluorescent probes have received more and more attentions. Currently, reported endoplasmic reticulum-targetable fluorescent probes mainly include simple endoplasmic reticulum imaging, metal ions, small molecule material, big molecule material, microenvironments, etc. This article summarizes and describes the design and synthesis of the reported endoplasmic reticulum-targetable fluorescent probes, analyzes the application of endoplasmic reticulum fluorescent probes in the study of cellular physiological processes, and prospects the development trend of endoplasmic reticulum-targetable fluorescent probes.
The endoplasmic reticulum, a subcellular organelle, plays an important role in the life activities of mammalian cells. Therefore, visualizing the endoplasmic reticulum, and further examining its active substances, microenvironments and physiological processes have important guiding value for the diagnosis and treatment of related diseases. In recent years, the design and synthesis of endoplasmic reticulum-targetable fluorescent probes have received more and more attentions. Currently, reported endoplasmic reticulum-targetable fluorescent probes mainly include simple endoplasmic reticulum imaging, metal ions, small molecule material, big molecule material, microenvironments, etc. This article summarizes and describes the design and synthesis of the reported endoplasmic reticulum-targetable fluorescent probes, analyzes the application of endoplasmic reticulum fluorescent probes in the study of cellular physiological processes, and prospects the development trend of endoplasmic reticulum-targetable fluorescent probes.
2018, 38(12): 3176-3188
doi: 10.6023/cjoc201805010
Abstract:
In recent years, ionic liquids have been extensively studied in the laboratory and industrial fields due to their unique properties and have shown good application prospects. At the same time, a series of ionic liquids green preparation technologies have been developed and designed, which has greatly changed the research aspect of ionic liquids. In this paper, the green preparation of ionic liquids and their application in environmental remediation are reviewed. The synthesis processes of ionic liquids, including atoms economic reaction, green raw materials reaction, green solvents reaction, chemical process intensification and computer-aided design are emphasized with reference to their advantages of high synthesis efficiency, good product quality, low waste generation, low energy consumption, mild conditions and etc. Moreover, the green preparation of ionic liquids not only makes the ionic liquid more abundant, but also makes it absolutely a green solvent and green functional material. The typical characteristics that reflect the unique advantages of ionic liquids in environmental restoration are as follows. In terms of water body restoration, it has the characteristics of high separation efficiency, elimination of secondary pollution and less consumables. In the soil remediation, it can effectively reduce the toxicity of pollutants in soil. In the atmospheric remediation, it eliminates pollutants and sometimes achieves the resource utilization. Furthermore, the future development trend of ionic liquids in green preparation and environmental remediation is also prospected.
In recent years, ionic liquids have been extensively studied in the laboratory and industrial fields due to their unique properties and have shown good application prospects. At the same time, a series of ionic liquids green preparation technologies have been developed and designed, which has greatly changed the research aspect of ionic liquids. In this paper, the green preparation of ionic liquids and their application in environmental remediation are reviewed. The synthesis processes of ionic liquids, including atoms economic reaction, green raw materials reaction, green solvents reaction, chemical process intensification and computer-aided design are emphasized with reference to their advantages of high synthesis efficiency, good product quality, low waste generation, low energy consumption, mild conditions and etc. Moreover, the green preparation of ionic liquids not only makes the ionic liquid more abundant, but also makes it absolutely a green solvent and green functional material. The typical characteristics that reflect the unique advantages of ionic liquids in environmental restoration are as follows. In terms of water body restoration, it has the characteristics of high separation efficiency, elimination of secondary pollution and less consumables. In the soil remediation, it can effectively reduce the toxicity of pollutants in soil. In the atmospheric remediation, it eliminates pollutants and sometimes achieves the resource utilization. Furthermore, the future development trend of ionic liquids in green preparation and environmental remediation is also prospected.
2018, 38(12): 3189-3196
doi: 10.6023/cjoc201807014
Abstract:
A simple and practical visible-light-induced protocol has been developed for the construction of 3-arylquinoxa-lin-2(1H)-ones via Eosin Y-catalyzed direct C-H 3-arylation of quinoxalin-2(H)-ones with aryl diazonium salts at room temperature in air. The present reaction provides a cost-effective and operationally straightforward approach to the target products in moderate to good yields, and does not require any metal reagents, bases, acids, and strong oxidants.
A simple and practical visible-light-induced protocol has been developed for the construction of 3-arylquinoxa-lin-2(1H)-ones via Eosin Y-catalyzed direct C-H 3-arylation of quinoxalin-2(H)-ones with aryl diazonium salts at room temperature in air. The present reaction provides a cost-effective and operationally straightforward approach to the target products in moderate to good yields, and does not require any metal reagents, bases, acids, and strong oxidants.
Synthesis and Anti-fungual Activity of Novel Aspernigerin Derivatives Containing Thiocarbonyl Moiety
2018, 38(12): 3197-3203
doi: 10.6023/cjoc201807004
Abstract:
Based on the structure of natural product aspernigerin, a series of novel tetrahydroquinoline compounds containing thiocarbonyl moiety were designed and synthesized. The structures of the title compounds were confirmed by 1H NMR, 13C NMR and HRMS, and the crystal structure of (E)-3-(4-fluorophenyl)-1-(4-(1, 2, 3, 4-tetrahydroquinoline-1-carbonothioyl) piperazin-1-yl)prop-2-en-1-one (5J) was determined by X-ray single crystal diffraction. The bioassay results indicated that (E)-1-(4-(1, 2, 3, 4-tetrahydroquinoline-1-carbonothioyl)piperazin-1-yl)-3-(o-tolyl)prop-2-en-1-one (5b) exhibited good anti-fungual activity against Valsa mali (EC50=3.04 μg/mL), which was better than the commercial fungicide fluoramide (EC50=9.16 μg/mL).
Based on the structure of natural product aspernigerin, a series of novel tetrahydroquinoline compounds containing thiocarbonyl moiety were designed and synthesized. The structures of the title compounds were confirmed by 1H NMR, 13C NMR and HRMS, and the crystal structure of (E)-3-(4-fluorophenyl)-1-(4-(1, 2, 3, 4-tetrahydroquinoline-1-carbonothioyl) piperazin-1-yl)prop-2-en-1-one (5J) was determined by X-ray single crystal diffraction. The bioassay results indicated that (E)-1-(4-(1, 2, 3, 4-tetrahydroquinoline-1-carbonothioyl)piperazin-1-yl)-3-(o-tolyl)prop-2-en-1-one (5b) exhibited good anti-fungual activity against Valsa mali (EC50=3.04 μg/mL), which was better than the commercial fungicide fluoramide (EC50=9.16 μg/mL).
2018, 38(12): 3204-3210
doi: 10.6023/cjoc201806015
Abstract:
Human DNA Topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. Our previous study showed that p-terphenyls have inhibitory effects on Topo Ⅱα and inhibit the proliferation of human breast ductal carcinoma cells. In this study, nineteen 6-substituted aryl-2-methoxyquinolines (3a~3s) were designed, synthesized and evaluated for their cytotoxicity against the growth of human triple negative breast cancer MDA-MB-231 cell line and inhibitory activity against Topo Ⅱα. Among these compounds, 6-(4-(hydroxymethyl)phenyl)-2-methoxyquinoline (3b) showed the most potent activity (IC50=9.9 μmol·L-1). These results have important significance for the further study of aryl quinoline TopoⅡα inhibitors.
Human DNA Topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. Our previous study showed that p-terphenyls have inhibitory effects on Topo Ⅱα and inhibit the proliferation of human breast ductal carcinoma cells. In this study, nineteen 6-substituted aryl-2-methoxyquinolines (3a~3s) were designed, synthesized and evaluated for their cytotoxicity against the growth of human triple negative breast cancer MDA-MB-231 cell line and inhibitory activity against Topo Ⅱα. Among these compounds, 6-(4-(hydroxymethyl)phenyl)-2-methoxyquinoline (3b) showed the most potent activity (IC50=9.9 μmol·L-1). These results have important significance for the further study of aryl quinoline TopoⅡα inhibitors.
2018, 38(12): 3219-3226
doi: 10.6023/cjoc201805007
Abstract:
Two novel nitrogen-containing rigid heterocycle substituted coumarin sensitizing dyes were designed and synthesized with nitrogen-containing rigid heterocycle substituted coumarin as the electron donor, biphenyl or phenylthiophene as π bridge and cyanoacrylic acid as the electron acceptor. Their spectral properties, charge recombination rate and photovoltaic performance were compared with those of the corresponding diethylaminocoumarin sensitizing dyes. The results show that the incorporation of nitrogen-containing rigid heterocycle leads to the broadening of the absorption spectrum and the improvement of light-harvesting ability. In the dye with phenylthiophene as π bridge, the presence of nitrogen-containing rigid heterocycle distinctly weakens the molecular planarity, decreases the charge recombination rate and improves VOC. Therefore, among four coumarin sensitizing dyes, nitrogen-containing rigid heterocycle coumarin sensitizing dye with phenylthiophene π bridge exhibits the optimal photoelectric conversion efficiency 3.89% due to its better JSC, highest VOC and fill factor (ff).
Two novel nitrogen-containing rigid heterocycle substituted coumarin sensitizing dyes were designed and synthesized with nitrogen-containing rigid heterocycle substituted coumarin as the electron donor, biphenyl or phenylthiophene as π bridge and cyanoacrylic acid as the electron acceptor. Their spectral properties, charge recombination rate and photovoltaic performance were compared with those of the corresponding diethylaminocoumarin sensitizing dyes. The results show that the incorporation of nitrogen-containing rigid heterocycle leads to the broadening of the absorption spectrum and the improvement of light-harvesting ability. In the dye with phenylthiophene as π bridge, the presence of nitrogen-containing rigid heterocycle distinctly weakens the molecular planarity, decreases the charge recombination rate and improves VOC. Therefore, among four coumarin sensitizing dyes, nitrogen-containing rigid heterocycle coumarin sensitizing dye with phenylthiophene π bridge exhibits the optimal photoelectric conversion efficiency 3.89% due to its better JSC, highest VOC and fill factor (ff).
2018, 38(12): 3227-3235
doi: 10.6023/cjoc201805030
Abstract:
Twenty oleanolic acid and ursolic acid derivatives were prepared by a modification at C-28 position via introduction with 1, 5-pentanedioic acid and glycolic acid followed by amidation with amines, such as morpholine, N-methyl piperazine and N-Boc-ethylenediamine. Their in vitro anticancer activities towards A549, MCF-7 and HepG2 cell lines were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl tetrazolium bromide (MTT) method. The results indicated that the anticancer activities of olean-2, 12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (OA-9d), urs-2, 12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (UA-9d) against A549, MCF-7 and HepG2 cells are obviously better than those of lead compounds. The ability of UA-9d to inhibit the expression of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma Hep3B cells was determined by hypoxia response element (HRE)-dependent molecular assay. The results showed that UA-9d could effectively inhibit the expression of HIF-1α.
Twenty oleanolic acid and ursolic acid derivatives were prepared by a modification at C-28 position via introduction with 1, 5-pentanedioic acid and glycolic acid followed by amidation with amines, such as morpholine, N-methyl piperazine and N-Boc-ethylenediamine. Their in vitro anticancer activities towards A549, MCF-7 and HepG2 cell lines were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl tetrazolium bromide (MTT) method. The results indicated that the anticancer activities of olean-2, 12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (OA-9d), urs-2, 12-diene-28-oic acid[1-(2-amino-ethylamino)-1-oxo]ethyl ester (UA-9d) against A549, MCF-7 and HepG2 cells are obviously better than those of lead compounds. The ability of UA-9d to inhibit the expression of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma Hep3B cells was determined by hypoxia response element (HRE)-dependent molecular assay. The results showed that UA-9d could effectively inhibit the expression of HIF-1α.
Ruthenium(Ⅱ)-Catalyzed C-H Bond Regioselective[3+2] Annulation of Arylamines with Propargyl Alcohols
2018, 38(12): 3242-3249
doi: 10.6023/cjoc201806039
Abstract:
A simple and efficient ruthenium(Ⅱ)-catalyzed C-H bond regioselective[3+2] annulation of arylamines with propargyl alcohols has been reported. This protocol provides a facile approach to hydroxy-containing indole skeleton, which could be employed for constructing more complex and useful pharmaceutical molecules. Meantime, the kinetic isotope effect was further investigated and the results indicated that the C-H bond-breaking was possibly involved in the rate-limiting step of this transformation.
A simple and efficient ruthenium(Ⅱ)-catalyzed C-H bond regioselective[3+2] annulation of arylamines with propargyl alcohols has been reported. This protocol provides a facile approach to hydroxy-containing indole skeleton, which could be employed for constructing more complex and useful pharmaceutical molecules. Meantime, the kinetic isotope effect was further investigated and the results indicated that the C-H bond-breaking was possibly involved in the rate-limiting step of this transformation.
2018, 38(12): 3250-3259
doi: 10.6023/cjoc201806046
Abstract:
In order to expand study and application for the chlorophllous chlorins, pyropheophorbide-a methyl ester was used as a starting material. The chemical modifications and structural transformations along the terminals of N21-N23 axis were carried out to build active electron-accepting functional structures such as aldehyde, α-diketone, enenitrile and ketene moieties. The cyclizations with different electron-sufficient systems were accomplished to synthesize a series of unreported chlorins related to chlorophyll with multiple heterocyclic structures. The chemical structures of new compounds were characterized by elemental analysis, MS, UV-Vis, IR and 1H NMR spectra. Meanwhile the relevant formation process of the heterocyclic ring, the stereochemistry selectivity and the change of the electronic spectrum were discussed.
In order to expand study and application for the chlorophllous chlorins, pyropheophorbide-a methyl ester was used as a starting material. The chemical modifications and structural transformations along the terminals of N21-N23 axis were carried out to build active electron-accepting functional structures such as aldehyde, α-diketone, enenitrile and ketene moieties. The cyclizations with different electron-sufficient systems were accomplished to synthesize a series of unreported chlorins related to chlorophyll with multiple heterocyclic structures. The chemical structures of new compounds were characterized by elemental analysis, MS, UV-Vis, IR and 1H NMR spectra. Meanwhile the relevant formation process of the heterocyclic ring, the stereochemistry selectivity and the change of the electronic spectrum were discussed.
2018, 38(12): 3260-3269
doi: 10.6023/cjoc201806014
Abstract:
Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are one of the most prominent fluorosurfactants and these compounds have the most widely applications. However, such fluorocarbon surfactants have been listed as one of the most difficult to degrade organic pollutants in nature. Perfluoro-2-methyl-2-pentene was used as starting material to introducing fluorinated branch for synthesizing non-bioaccumulable alternatives. Fluorinated surfactants containing CF3CF2CF2C(CF3)2 group were successfully synthesized. The surface tension tests showed the hydrophilic groups have a great influence on the surface properties in aqueous solution, and the compound showed the best surface activities when the hydrophilic group was ammonium oxide. The length of the linking group and the size of the hydrophilic group have a general effect on the surface activity, but increasing the rigidity of the two groups can effectively increase the surface activity. The carbonyl group in the surfactant compound and the positively charged nitrogen atom will produce intramolecular interactions, enhance the rigidity of the molecule, and thus increase the surface activity. The critical micelle concentration (cmc) value of the fluorinated surfactant with ammonium oxide as headgroup was about 1.73×10-2 mol/L and the surface tension in water was 19.93 mN/m at the cmc. A excellent synergism was found when it was mixed with APG0810, the use of fluorocarbon surfactant can be reduced by a factor of 100, whereas the surface tension is basically unchanged.
Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are one of the most prominent fluorosurfactants and these compounds have the most widely applications. However, such fluorocarbon surfactants have been listed as one of the most difficult to degrade organic pollutants in nature. Perfluoro-2-methyl-2-pentene was used as starting material to introducing fluorinated branch for synthesizing non-bioaccumulable alternatives. Fluorinated surfactants containing CF3CF2CF2C(CF3)2 group were successfully synthesized. The surface tension tests showed the hydrophilic groups have a great influence on the surface properties in aqueous solution, and the compound showed the best surface activities when the hydrophilic group was ammonium oxide. The length of the linking group and the size of the hydrophilic group have a general effect on the surface activity, but increasing the rigidity of the two groups can effectively increase the surface activity. The carbonyl group in the surfactant compound and the positively charged nitrogen atom will produce intramolecular interactions, enhance the rigidity of the molecule, and thus increase the surface activity. The critical micelle concentration (cmc) value of the fluorinated surfactant with ammonium oxide as headgroup was about 1.73×10-2 mol/L and the surface tension in water was 19.93 mN/m at the cmc. A excellent synergism was found when it was mixed with APG0810, the use of fluorocarbon surfactant can be reduced by a factor of 100, whereas the surface tension is basically unchanged.
2018, 38(12): 3278-3285
doi: 10.6023/cjoc201804020
Abstract:
A series of novel aryl-substituted imidazo[1, 2-a]pyrimidine and triazolo[1, 5-a] pyrimidine were synthesized by the tandem reaction of Knoevenagel and Atwal modified Biginelli, following by aromatization. Some of their cytotoxic activities against Hela and A549 cells and inhibition for apple tree canker were preliminarily evaluated.
A series of novel aryl-substituted imidazo[1, 2-a]pyrimidine and triazolo[1, 5-a] pyrimidine were synthesized by the tandem reaction of Knoevenagel and Atwal modified Biginelli, following by aromatization. Some of their cytotoxic activities against Hela and A549 cells and inhibition for apple tree canker were preliminarily evaluated.
2018, 38(12): 3286-3295
doi: 10.6023/cjoc201805050
Abstract:
Reactions of OsCl2(PPh3)3 (1) with bidentate nitrogen-based ligands at room temperature led to the formation of complexes OsCl2(PPh3)2(diamine) (2~6) and OsCl2(PPh3)2(Phen*) (7~11). Complexes 2~11 showed high activity in the catalytic dehydrogenation of ammonia borane at 60℃, in THF/DME (V:V=1:1.6) solution with the catalyst loading of 5 mol%. Among all the catalysts, compound 4 demonstrated the highest catalytic activity, which represents the most efficient osmium catalyst in catalytic dehydrogenation of ammonia borane until now.
Reactions of OsCl2(PPh3)3 (1) with bidentate nitrogen-based ligands at room temperature led to the formation of complexes OsCl2(PPh3)2(diamine) (2~6) and OsCl2(PPh3)2(Phen*) (7~11). Complexes 2~11 showed high activity in the catalytic dehydrogenation of ammonia borane at 60℃, in THF/DME (V:V=1:1.6) solution with the catalyst loading of 5 mol%. Among all the catalysts, compound 4 demonstrated the highest catalytic activity, which represents the most efficient osmium catalyst in catalytic dehydrogenation of ammonia borane until now.
2018, 38(12): 3296-3301
doi: 10.6023/cjoc201805019
Abstract:
Alanine triazole Mn-catalyzed 1, 6-conjugate coupling/aromatization of para-quinone methides was developed with good to high yields under mild conditions. This protocol provided an efficient and practical route to the synthetically interesting functionalized methines and their analogues. Preliminary mechanistic experiments revealed 1, 6-conjugate addition of nucleophiles to para-quinone methides (p-QMs). The manganese was acted as the Lewis acid.
Alanine triazole Mn-catalyzed 1, 6-conjugate coupling/aromatization of para-quinone methides was developed with good to high yields under mild conditions. This protocol provided an efficient and practical route to the synthetically interesting functionalized methines and their analogues. Preliminary mechanistic experiments revealed 1, 6-conjugate addition of nucleophiles to para-quinone methides (p-QMs). The manganese was acted as the Lewis acid.
2018, 38(12): 3211-3218
doi: 10.6023/cjoc201805022
Abstract:
Direct synthesis of the hydroxymethylated arene derivatives via ruthenium(Ⅲ)-catalyzed nitrogen atom directed C-H activation is described. The reaction proceeds smoothly at room temperature and generates the corresponding products in moderate to excellent yields. Meanwhile, it has a broad substrate scope and opens up an attractive avenue for the application of direct hydroxymethylation in the synthesis of biologically active compounds.
Direct synthesis of the hydroxymethylated arene derivatives via ruthenium(Ⅲ)-catalyzed nitrogen atom directed C-H activation is described. The reaction proceeds smoothly at room temperature and generates the corresponding products in moderate to excellent yields. Meanwhile, it has a broad substrate scope and opens up an attractive avenue for the application of direct hydroxymethylation in the synthesis of biologically active compounds.
2018, 38(12): 3236-3241
doi: 10.6023/cjoc201806026
Abstract:
A variety of mono-, di-, and tri-substituted (aryl, alkyl, and/or alkenyl) isoxazoles were synthesized from readily accessible α, β-unsaturated oximes via I2-mediated oxidative C-O bond formation. The features of this synthetic approach include no use of transition metals, simple operation, mild reaction conditions, short reaction time, and broad substrate scope.
A variety of mono-, di-, and tri-substituted (aryl, alkyl, and/or alkenyl) isoxazoles were synthesized from readily accessible α, β-unsaturated oximes via I2-mediated oxidative C-O bond formation. The features of this synthetic approach include no use of transition metals, simple operation, mild reaction conditions, short reaction time, and broad substrate scope.
2018, 38(12): 3270-3277
doi: 10.6023/cjoc201805005
Abstract:
In order to find novel antitumor agents with high efficiency and low toxicity, 11 novel pyrrolo[2, 1-f] [1, 2, 4]triazine derivatives were designed and synthesized through the introduction of varied structural moieties to the 4, 6-positions of pyrrolotriazine core. The antiproliferative activities of synthesized compounds were also evaluated against human tumor cells. Firstly, 2-amino-2-cyanoacetamide (1) was prepared from methyl cyanoacetate as a starting material through three step reactions of oximation, reduction and ammonolysis. Meanwhile, ethyl 2-acetyl-3-(dimethylamino)acrylate (2) was obtained from the reaction of ethyl acetoacetate with N, N-dimethylformamide dimethyl acetal. Then the cyclization reaction of 1 with 2 gave ethyl 5-cyano-4-methylpyrrole-3-carboxylate (4). Finally, pyrrolotriazine derivatives as target compounds were synthesized from 4 through the ammoniation, generating amidine, Dimroth rearrangement, and subsequent hydrolyzation and acylation. The antiproliferative activities of target compounds against human tumor cell lines were investigated by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The results demonstrated that most synthesized compounds had obviously selective inhibitory effects against A431 cells with highly expressed wild type epidermal growth factor receptor (EGFR). Ethyl 4-(3-ethynylphenylamino)-5-methylpyrrolo[2, 1-f] [1, 2, 4]triazine-6-carboxylate (7c), 4-(3-chloro-4-(3-fluorobenzyloxy)phenyl-amino)-5-methylpyrrolo[2, 1-f] [1, 2, 4]triazine-6-carboxylic acid (8a) and 4-(3-ethynylphenylamino)-5-methylpyrrolo[2, 1-f]-[1, 2, 4]triazine-6-(N-(2-(methylsulfonyl)ethyl))carboxamide (9c) were the most potent agents with IC50 values of 20.05, 21.98 and 23.87 μmol·L-1 in the synthesized compounds, respectively. Preliminary structure-activity relationship analysis indicated that the introduction of 3-chloro-4-(3-fluorobenzyloxy)phenylamino and 3-ethynylphenylamino to 4-position of pyrrolotriazine-6-carboxylic acids or its esters can lead to enhance antiproliferative activities against A431 tumour cells.
In order to find novel antitumor agents with high efficiency and low toxicity, 11 novel pyrrolo[2, 1-f] [1, 2, 4]triazine derivatives were designed and synthesized through the introduction of varied structural moieties to the 4, 6-positions of pyrrolotriazine core. The antiproliferative activities of synthesized compounds were also evaluated against human tumor cells. Firstly, 2-amino-2-cyanoacetamide (1) was prepared from methyl cyanoacetate as a starting material through three step reactions of oximation, reduction and ammonolysis. Meanwhile, ethyl 2-acetyl-3-(dimethylamino)acrylate (2) was obtained from the reaction of ethyl acetoacetate with N, N-dimethylformamide dimethyl acetal. Then the cyclization reaction of 1 with 2 gave ethyl 5-cyano-4-methylpyrrole-3-carboxylate (4). Finally, pyrrolotriazine derivatives as target compounds were synthesized from 4 through the ammoniation, generating amidine, Dimroth rearrangement, and subsequent hydrolyzation and acylation. The antiproliferative activities of target compounds against human tumor cell lines were investigated by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The results demonstrated that most synthesized compounds had obviously selective inhibitory effects against A431 cells with highly expressed wild type epidermal growth factor receptor (EGFR). Ethyl 4-(3-ethynylphenylamino)-5-methylpyrrolo[2, 1-f] [1, 2, 4]triazine-6-carboxylate (7c), 4-(3-chloro-4-(3-fluorobenzyloxy)phenyl-amino)-5-methylpyrrolo[2, 1-f] [1, 2, 4]triazine-6-carboxylic acid (8a) and 4-(3-ethynylphenylamino)-5-methylpyrrolo[2, 1-f]-[1, 2, 4]triazine-6-(N-(2-(methylsulfonyl)ethyl))carboxamide (9c) were the most potent agents with IC50 values of 20.05, 21.98 and 23.87 μmol·L-1 in the synthesized compounds, respectively. Preliminary structure-activity relationship analysis indicated that the introduction of 3-chloro-4-(3-fluorobenzyloxy)phenylamino and 3-ethynylphenylamino to 4-position of pyrrolotriazine-6-carboxylic acids or its esters can lead to enhance antiproliferative activities against A431 tumour cells.
2018, 38(12): 3302-3317
doi: 10.6023/cjoc201807019
Abstract:
In order to further expand the molecular diversity of quinone-fused imidazoles as anticancer agents, a number of 1-monosubstituted 1H-naphtho[2, 3-d]imidazole-4, 9-diones and 1H-anthra[2, 3-d]imidazole-4, 11-diones were designed, synthesized and biologically evaluated. The structure-activity relationships were studied in vitro against three human cancer cell lines (human breast carcinoma cell line MCF-7, human cervical carcinoma cell line Hela and human lung carcinoma cell line A549) and one normal cell line (mouse fibroblast cell line L929). Among them, 1-methyl-1H-anthra[2, 3-d]imidazole-4, 11-dione, which bears a large π-system and a small N-substituent in the imidazole segment, showed good antiproliferative activity against MCF-7 and A549 (IC50 values are 7.4 and 1.6 μmol·L-1, respectively) and almost no cytotoxicity to L929 (IC50 is 150 μmol·L-1).
In order to further expand the molecular diversity of quinone-fused imidazoles as anticancer agents, a number of 1-monosubstituted 1H-naphtho[2, 3-d]imidazole-4, 9-diones and 1H-anthra[2, 3-d]imidazole-4, 11-diones were designed, synthesized and biologically evaluated. The structure-activity relationships were studied in vitro against three human cancer cell lines (human breast carcinoma cell line MCF-7, human cervical carcinoma cell line Hela and human lung carcinoma cell line A549) and one normal cell line (mouse fibroblast cell line L929). Among them, 1-methyl-1H-anthra[2, 3-d]imidazole-4, 11-dione, which bears a large π-system and a small N-substituent in the imidazole segment, showed good antiproliferative activity against MCF-7 and A549 (IC50 values are 7.4 and 1.6 μmol·L-1, respectively) and almost no cytotoxicity to L929 (IC50 is 150 μmol·L-1).
2018, 38(12): 3318-3325
doi: 10.6023/cjoc201807048
Abstract:
In order to find new pyrazole oxime ether derivatives with potent bioactivities, fifteen novel pyrazole oxime ethers containing an oxazole moiety were designed and prepared according to the method of active substructure combination. Their structures were confirmed through 1H NMR, 13C NMR, and elemental analysis. Preliminary bioassay showed that most of the title compounds displayed wonderful insecticidal activities against Oriental armyworm, Aphis medicaginis and Tetranychus cinnabarinus. At the concentration of 500 μg/mL, ten compounds exhibited acaricidal activity against Tetranychus cinnabarinus with over 80%, especially four compounds indicated comparable insecticidal activity against Tetranychus cinnabarinus to that of the control of fenpyroximate, the lethal rates of nine compounds against Aphis medicaginis were all 100%, which were near to that of imidacloprid, and the lethal rates of fourteen compounds against Oriental armyworm were all 100%, which were similar to that of pyridalyl. At the concentration of 100 μg/mL, the lethal rates of three compounds against Tetranychus cinnabarinus were all 60%, and the lethal rates of two compounds against Aphis medicaginis were 90% and 100%. When the concentration was reduced to 20 μg/mL, compound 1, 3-dimethyl-5-(4-methylphenoxy)-1H-pyrazole-4-carbaldehyde-O-[4-(oxazol-5-yl)phenylmethyl]oxime (7i) still had insecticidal activity against Aphis medicaginis with 60%.
In order to find new pyrazole oxime ether derivatives with potent bioactivities, fifteen novel pyrazole oxime ethers containing an oxazole moiety were designed and prepared according to the method of active substructure combination. Their structures were confirmed through 1H NMR, 13C NMR, and elemental analysis. Preliminary bioassay showed that most of the title compounds displayed wonderful insecticidal activities against Oriental armyworm, Aphis medicaginis and Tetranychus cinnabarinus. At the concentration of 500 μg/mL, ten compounds exhibited acaricidal activity against Tetranychus cinnabarinus with over 80%, especially four compounds indicated comparable insecticidal activity against Tetranychus cinnabarinus to that of the control of fenpyroximate, the lethal rates of nine compounds against Aphis medicaginis were all 100%, which were near to that of imidacloprid, and the lethal rates of fourteen compounds against Oriental armyworm were all 100%, which were similar to that of pyridalyl. At the concentration of 100 μg/mL, the lethal rates of three compounds against Tetranychus cinnabarinus were all 60%, and the lethal rates of two compounds against Aphis medicaginis were 90% and 100%. When the concentration was reduced to 20 μg/mL, compound 1, 3-dimethyl-5-(4-methylphenoxy)-1H-pyrazole-4-carbaldehyde-O-[4-(oxazol-5-yl)phenylmethyl]oxime (7i) still had insecticidal activity against Aphis medicaginis with 60%.
2018, 38(12): 3332-3337
doi: 10.6023/cjoc201806025
Abstract:
Tetri/pentitolyl benzimidazoles were prepared by using the unprotected monosaccharides and o-phenylenediamine as the starting materials. Intramolecular dehydration of the oligotoltyl benzimidazoles afforded two furanosyl benzimidazole C-nucleosides (α/β isomers) through Mitsunoble reaction. One isomer was the configuration-retension product, the other was the configuration-inversion one. The regioselectivity of Mitsunobu reaction is good, which provides an effective protocol for the synthesis of furanosyl benzimidazole C-nucleosides.
Tetri/pentitolyl benzimidazoles were prepared by using the unprotected monosaccharides and o-phenylenediamine as the starting materials. Intramolecular dehydration of the oligotoltyl benzimidazoles afforded two furanosyl benzimidazole C-nucleosides (α/β isomers) through Mitsunoble reaction. One isomer was the configuration-retension product, the other was the configuration-inversion one. The regioselectivity of Mitsunobu reaction is good, which provides an effective protocol for the synthesis of furanosyl benzimidazole C-nucleosides.
2018, 38(12): 3345-3350
doi: 10.6023/cjoc201806007
Abstract:
Aromatic-fused pyran-4-one skeleton exists in many natural and synthetic biologically active materials. An efficient method for the transformation of naphthyl 3-methylcrotonate to 2, 3-dihydro-benzo[f]chromen-1-one catalyzed by ferric chloride is described, which provides a practical process to afford this type of biologically important compounds in good yields using commercially available and inexpensive catalyst. A two-step mechanism involving Fries rearrangement and intramolecular hydroalkoxylation is proposed.
Aromatic-fused pyran-4-one skeleton exists in many natural and synthetic biologically active materials. An efficient method for the transformation of naphthyl 3-methylcrotonate to 2, 3-dihydro-benzo[f]chromen-1-one catalyzed by ferric chloride is described, which provides a practical process to afford this type of biologically important compounds in good yields using commercially available and inexpensive catalyst. A two-step mechanism involving Fries rearrangement and intramolecular hydroalkoxylation is proposed.
2018, 38(12): 3351-3355
doi: 10.6023/cjoc201806028
Abstract:
The first total synthesis of marine natural nucleoside kipukasin D was disclosed in 9 steps and 15.7% overall yield using commercially available tetra-O-acetyl-β-D-ribose as starting material. In Vorbrüggen glycosylation, ortho-iodinebenzoate acted as neighboring participating group leading to β-nucleoside. The key step was selectively deprotection of 2'-O and 5'-O ortho-alkynylbenzoates by freshing prepared Ph3PAuOTFA in the presence of ethanol (6 equiv.) and H2O (1 equiv.) in dichloromethane (DCM). The reaction condition of our newly developed approach is very mild and neutral, which effectively avoids the transesterification between 2'-OH and 3'-OH. The result further demonstrat that ortho-alkynylbenzoate is an orthogonal protecting group compatible with other ester groups, which could find wide applications in nucleoside and carbohydrate chemistry.
The first total synthesis of marine natural nucleoside kipukasin D was disclosed in 9 steps and 15.7% overall yield using commercially available tetra-O-acetyl-β-D-ribose as starting material. In Vorbrüggen glycosylation, ortho-iodinebenzoate acted as neighboring participating group leading to β-nucleoside. The key step was selectively deprotection of 2'-O and 5'-O ortho-alkynylbenzoates by freshing prepared Ph3PAuOTFA in the presence of ethanol (6 equiv.) and H2O (1 equiv.) in dichloromethane (DCM). The reaction condition of our newly developed approach is very mild and neutral, which effectively avoids the transesterification between 2'-OH and 3'-OH. The result further demonstrat that ortho-alkynylbenzoate is an orthogonal protecting group compatible with other ester groups, which could find wide applications in nucleoside and carbohydrate chemistry.
2018, 38(12): 3363-3372
doi: 10.6023/cjoc201807001
Abstract:
Spinosyns are a novel kind of biopesticide produced by Saccharopolyspora spinosa. Spinosyns have been widely applied in pest control because of their broad insecticidal spectrum, high insecticidal activity, low environmental impact, and low toxicity. To identify spinosyn compounds with improved insecticidal activity, a series of D-forosamine replacement derivatives of spinosyn A were synthesized. The insecticidal activities of the synthetic derivatives were evaluated against 3rd-instar larvae of Plutella xylostella. All derivatives exhibited good insecticidal activity to P. xylostella.
Spinosyns are a novel kind of biopesticide produced by Saccharopolyspora spinosa. Spinosyns have been widely applied in pest control because of their broad insecticidal spectrum, high insecticidal activity, low environmental impact, and low toxicity. To identify spinosyn compounds with improved insecticidal activity, a series of D-forosamine replacement derivatives of spinosyn A were synthesized. The insecticidal activities of the synthetic derivatives were evaluated against 3rd-instar larvae of Plutella xylostella. All derivatives exhibited good insecticidal activity to P. xylostella.
2018, 38(12): 3373-3380
doi: 10.6023/cjoc201806010
Abstract:
A novel enantioselective organocatalytic cascade Michael-hemiaminalization-hemiacetalization reaction of α, β-unsaturated aldehydes with α-ketoamides as binucleophiles has been developed. A series of chiral functionalized bicyclic lactams with two cis contiguous stereogenic centers have been synthesized in up to 97% yield with up to >20:1 dr and up to >99% ee.
A novel enantioselective organocatalytic cascade Michael-hemiaminalization-hemiacetalization reaction of α, β-unsaturated aldehydes with α-ketoamides as binucleophiles has been developed. A series of chiral functionalized bicyclic lactams with two cis contiguous stereogenic centers have been synthesized in up to 97% yield with up to >20:1 dr and up to >99% ee.
2018, 38(12): 3386-3393
doi: 10.6023/cjoc201805012
Abstract:
A[1+1] Schiff base macrocyclic compound L containing isophthalamide unit and phenol rings has been synthesized from the reaction of precursors N, N'-(6-amino-2-pyridyl)-1, 3-dicarboximide with 5, 5'-methylene bis-salicylaldehyde by Schiff-base condensation. The macrocycle L was characterized via 1H NMR, FABMS, and elemental analysis. The crystal structure of L was determined by X-ray diffraction analysis, and it has a folded clamp conformation. In the crystal state of L, individual macrocycles were assembled into columnar structures with 1D channel through intermolecular hydrogen bonding and π-π stacking interactions. The results show that the macrocycle L displays a selective recognition ability for H2PO4- and HP2O73- anion respectively by the coordination reaction of L with a series of anions using UV-Vis absorption spectra technique. Furthermore, the coordination reaction of L with H2PO4- or HP2O73- anion was investigated via UV-Vis spectra, 1H NMR and the isothermal titration calorimeter (ITC) respectively. The stoichiometric ratio, the association constant (K) and the thermodynamic parameters (△rHm, △rSm and △rGm) of the coordination reaction were obtained. The results show that the macrocycle L binds H2PO4- with a 1:1 binding stoichiometry, and binds HP2O73- to form the structure of sandwich-type with a bonding ratio of 2:1.
A[1+1] Schiff base macrocyclic compound L containing isophthalamide unit and phenol rings has been synthesized from the reaction of precursors N, N'-(6-amino-2-pyridyl)-1, 3-dicarboximide with 5, 5'-methylene bis-salicylaldehyde by Schiff-base condensation. The macrocycle L was characterized via 1H NMR, FABMS, and elemental analysis. The crystal structure of L was determined by X-ray diffraction analysis, and it has a folded clamp conformation. In the crystal state of L, individual macrocycles were assembled into columnar structures with 1D channel through intermolecular hydrogen bonding and π-π stacking interactions. The results show that the macrocycle L displays a selective recognition ability for H2PO4- and HP2O73- anion respectively by the coordination reaction of L with a series of anions using UV-Vis absorption spectra technique. Furthermore, the coordination reaction of L with H2PO4- or HP2O73- anion was investigated via UV-Vis spectra, 1H NMR and the isothermal titration calorimeter (ITC) respectively. The stoichiometric ratio, the association constant (K) and the thermodynamic parameters (△rHm, △rSm and △rGm) of the coordination reaction were obtained. The results show that the macrocycle L binds H2PO4- with a 1:1 binding stoichiometry, and binds HP2O73- to form the structure of sandwich-type with a bonding ratio of 2:1.
2018, 38(12): 3326-3331
doi: 10.6023/cjoc201806044
Abstract:
A novel and practical cuprous bromide-catalyzed aerobic oxidation of benzylic alcohols with 1, 8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as the additive under air atmosphere has been developed. Various primary and secondary benzylic alcohols and allylic alcohols were smoothly transformed into the corresponding aldehydes and ketones with high yields and selectivity. The process is 2, 2, 6, 6-tetramethylpiperidin-1-oxyl (TEMPO) free and solvent-free.
A novel and practical cuprous bromide-catalyzed aerobic oxidation of benzylic alcohols with 1, 8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as the additive under air atmosphere has been developed. Various primary and secondary benzylic alcohols and allylic alcohols were smoothly transformed into the corresponding aldehydes and ketones with high yields and selectivity. The process is 2, 2, 6, 6-tetramethylpiperidin-1-oxyl (TEMPO) free and solvent-free.
2018, 38(12): 3338-3344
doi: 10.6023/cjoc201805011
Abstract:
A series of flavonoid-substituted Tröger's base analogues were synthesized via multi-step reaction. Their anti-cancer activities on the HepG2 hepatocellular carcinoma cell and antibacterial activities on four bacterial (Pseudomonas aeruginosa PAM1032, wild type Staphylococcus aureus, wild type Escherichia coli and Escherichia.coli-NMD-1) were evaluated. Two compounds were screened out because of their high inhibitory rate on Staphylococcus aureus at 1 μg/mL. The IC50 values of five products on the HepG2 (hepatocellular carcinoma cell) were lower than that of positive control paclitaxel (30.87 μg/mL), displaying their high inhibitory activity. The results indicated their potential applications in new drug development.
A series of flavonoid-substituted Tröger's base analogues were synthesized via multi-step reaction. Their anti-cancer activities on the HepG2 hepatocellular carcinoma cell and antibacterial activities on four bacterial (Pseudomonas aeruginosa PAM1032, wild type Staphylococcus aureus, wild type Escherichia coli and Escherichia.coli-NMD-1) were evaluated. Two compounds were screened out because of their high inhibitory rate on Staphylococcus aureus at 1 μg/mL. The IC50 values of five products on the HepG2 (hepatocellular carcinoma cell) were lower than that of positive control paclitaxel (30.87 μg/mL), displaying their high inhibitory activity. The results indicated their potential applications in new drug development.
2018, 38(12): 3356-3362
doi: 10.6023/cjoc201805053
Abstract:
In order to discover novel compounds with biological activities, new molecular hybrids combining benzimidazole or its bioisostere benzothiazole with β-carboline were synthesized. The benzimidazole or benzothiazole scaffold was linked at position-1 with β-carboline which was further characterized by 1H NMR, 13C NMR and HRMS. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg·mL-1. The preliminary results showed that most compounds exhibit mild inhibiting effect against all the tested strains. Among them, 1-(1H-benzo[d]-imida-zol-2-yl)-9-ethyl-β-carboline (4a), 1-(1H-benzo[d]imidazol-2-yl)-9-benzyl-β-carboline (4c) and 1-(1H-benzo[d]imidazol-2-yl)-9-(3-chlorobenzyl)-β-carboline (4e) showed satisfactory antifungal activity against sunflower sclerotinia rot, 1-(1H-benzo[d]-imidazol-2-yl)-9-ethyl-β-carboline (4a), 1-(1H-benzo[d]imidazol-2-yl)-9-n-butyl-β-carboline (4b), 1-(1H-benzo[d]imidazol-2-yl)-9-benzyl-β-carboline (4c), 1-(1H-benzo[d]imidazol-2-yl)-9-((perfluorophenyl)methyl)-β-carboline (4f), 1-(benzo[d]-thiazol-2-yl)-9-(3-chlorobenzyl)-β-carboline (5e) and 1-(benzo[d]thiazol-2-yl)-9-((perfluorophenyl)methyl)-β-carboline (5f) displayed excellent fungicidal activity against rape sclerotinia rot. Specifically, compound 4c exhibited broad-spectrum fungicidal activity against most of the tested fungi.
In order to discover novel compounds with biological activities, new molecular hybrids combining benzimidazole or its bioisostere benzothiazole with β-carboline were synthesized. The benzimidazole or benzothiazole scaffold was linked at position-1 with β-carboline which was further characterized by 1H NMR, 13C NMR and HRMS. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg·mL-1. The preliminary results showed that most compounds exhibit mild inhibiting effect against all the tested strains. Among them, 1-(1H-benzo[d]-imida-zol-2-yl)-9-ethyl-β-carboline (4a), 1-(1H-benzo[d]imidazol-2-yl)-9-benzyl-β-carboline (4c) and 1-(1H-benzo[d]imidazol-2-yl)-9-(3-chlorobenzyl)-β-carboline (4e) showed satisfactory antifungal activity against sunflower sclerotinia rot, 1-(1H-benzo[d]-imidazol-2-yl)-9-ethyl-β-carboline (4a), 1-(1H-benzo[d]imidazol-2-yl)-9-n-butyl-β-carboline (4b), 1-(1H-benzo[d]imidazol-2-yl)-9-benzyl-β-carboline (4c), 1-(1H-benzo[d]imidazol-2-yl)-9-((perfluorophenyl)methyl)-β-carboline (4f), 1-(benzo[d]-thiazol-2-yl)-9-(3-chlorobenzyl)-β-carboline (5e) and 1-(benzo[d]thiazol-2-yl)-9-((perfluorophenyl)methyl)-β-carboline (5f) displayed excellent fungicidal activity against rape sclerotinia rot. Specifically, compound 4c exhibited broad-spectrum fungicidal activity against most of the tested fungi.
2018, 38(12): 3381-3385
doi: 10.6023/cjoc201807003
Abstract:
A copper-catalyzed oxidative formal cycloaddition of 1, 3-dicarbonyl compounds, methanol and ammonium acetate was first demonstrated, affording symmetrical 2, 3, 5, 6-tetrasubstituted pyridines in moderate to excellent yields. Methanol was employed as the carbon synthon as well as the reaction solvent. The preliminary mechanistic studies revealed that the reaction underwent a radical pathway and the C(sp3)-H bond cleavage of methanol was the rate-determining step. This method is operationally simple and environmentally friendly.
A copper-catalyzed oxidative formal cycloaddition of 1, 3-dicarbonyl compounds, methanol and ammonium acetate was first demonstrated, affording symmetrical 2, 3, 5, 6-tetrasubstituted pyridines in moderate to excellent yields. Methanol was employed as the carbon synthon as well as the reaction solvent. The preliminary mechanistic studies revealed that the reaction underwent a radical pathway and the C(sp3)-H bond cleavage of methanol was the rate-determining step. This method is operationally simple and environmentally friendly.
