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2020 Volume 40 Issue 4
2020, 40(4): 817-830
doi: 10.6023/cjoc201910029
Abstract:
Benzofulvenes were widely found in natural products and bioactive molecules, and also served as important building blocks in material science and transition-metal chemistry. Great efforts have been devoted to the efficient synthesis of these interesting molecules, and rapid advancement has been made in the past two decades. According to the types of the initiation of the reaction, these methods can roughly be classified into five categories:thermal or photochemical cyclization of enyne-al-lenes or enediynes, transition metal-catalyzed sequential cyclization reaction, electrophilic or nucleophilic attack initiated cyclization, radical initiated cyclization and acid promoted cyclization. This review describes the important synthetic methods of benzofulvenes according to their reaction types.
Benzofulvenes were widely found in natural products and bioactive molecules, and also served as important building blocks in material science and transition-metal chemistry. Great efforts have been devoted to the efficient synthesis of these interesting molecules, and rapid advancement has been made in the past two decades. According to the types of the initiation of the reaction, these methods can roughly be classified into five categories:thermal or photochemical cyclization of enyne-al-lenes or enediynes, transition metal-catalyzed sequential cyclization reaction, electrophilic or nucleophilic attack initiated cyclization, radical initiated cyclization and acid promoted cyclization. This review describes the important synthetic methods of benzofulvenes according to their reaction types.
2020, 40(4): 831-855
doi: 10.6023/cjoc201910042
Abstract:
Organic π-conjugated polymers and small molecules, featured by low cost, light weight, solution processibility as well as finely adjustable structure and properties, have become kinds of fundamental semiconductor materials for next generation of optoelectric devices. The C—B/C—X Suzuki and C—Sn/C—X Stille couplings have become the most widely used strategy for the construction of sp2-C—C bonds involved in organic semiconductor materials. However, these traditional C—C coupling reactions usually involve prefunctionalization of subtrates and multipe synthetic steps, along with toxic by-products. In recent years, the direct C—H arylation reaction (C—H/C—X coupling) for the construction of sp2-C—C bonds and the synthesis of organic π-conjugated materials, featured by the simplicity without use of organometallic precursors, high atom- and step-econogy and low cost, has attracted extensive attention from researchers, due to its great potential for pratical applictions. The C—H/C—X direct arylation coupling has great potential in the efficient synthesis and practical application of organic optoelectric materials. Herein, an overview of recent developments in direct C—H arylation for the synthesis of organic conjugated functional materials used in device applications is provided, including organic photovoltaics (OPV), organic field effect transistor (OFET), dye-sensitized solar cell (DSSC), perovskite cells (PSC), organic light emitting diode (OLED) and lithium rattery, etc. The advantages, challenges as well as the future developments in the area of direct C—H arylation are also discussed and commented.
Organic π-conjugated polymers and small molecules, featured by low cost, light weight, solution processibility as well as finely adjustable structure and properties, have become kinds of fundamental semiconductor materials for next generation of optoelectric devices. The C—B/C—X Suzuki and C—Sn/C—X Stille couplings have become the most widely used strategy for the construction of sp2-C—C bonds involved in organic semiconductor materials. However, these traditional C—C coupling reactions usually involve prefunctionalization of subtrates and multipe synthetic steps, along with toxic by-products. In recent years, the direct C—H arylation reaction (C—H/C—X coupling) for the construction of sp2-C—C bonds and the synthesis of organic π-conjugated materials, featured by the simplicity without use of organometallic precursors, high atom- and step-econogy and low cost, has attracted extensive attention from researchers, due to its great potential for pratical applictions. The C—H/C—X direct arylation coupling has great potential in the efficient synthesis and practical application of organic optoelectric materials. Herein, an overview of recent developments in direct C—H arylation for the synthesis of organic conjugated functional materials used in device applications is provided, including organic photovoltaics (OPV), organic field effect transistor (OFET), dye-sensitized solar cell (DSSC), perovskite cells (PSC), organic light emitting diode (OLED) and lithium rattery, etc. The advantages, challenges as well as the future developments in the area of direct C—H arylation are also discussed and commented.
2020, 40(4): 856-872
doi: 10.6023/cjoc201910039
Abstract:
Organocatalytic multicomponent asymmetric cascade reaction is generally regarded as one of the most effective methods for constructing complex chiral compounds. Bifunctional chiral catalysts are an important class of single-molecule double-activated organic catalysts, which can simultaneously activate hydrogen bonds of multiple reactive substrates to achieve the formation of multiple new bonds and stereoselective control of multiple chiral centers. Nitroolefins are important organic reaction synthons, which can participate in a variety of asymmetric cascade reactions by hydrogen bond activation. In this paper, the recent advances in nitroolefins-involved multicomponent asymmetric cascade reactions catalyzed by bifunctional organocatalysts involving chiral bifunctional thiourea amines, squaramide amines and other bifunctional catalysts are reviewed. Specifically, the catalytic systems, characteristics, mechanisms are systematically expounded, and the application of this research field is also prospected.
Organocatalytic multicomponent asymmetric cascade reaction is generally regarded as one of the most effective methods for constructing complex chiral compounds. Bifunctional chiral catalysts are an important class of single-molecule double-activated organic catalysts, which can simultaneously activate hydrogen bonds of multiple reactive substrates to achieve the formation of multiple new bonds and stereoselective control of multiple chiral centers. Nitroolefins are important organic reaction synthons, which can participate in a variety of asymmetric cascade reactions by hydrogen bond activation. In this paper, the recent advances in nitroolefins-involved multicomponent asymmetric cascade reactions catalyzed by bifunctional organocatalysts involving chiral bifunctional thiourea amines, squaramide amines and other bifunctional catalysts are reviewed. Specifically, the catalytic systems, characteristics, mechanisms are systematically expounded, and the application of this research field is also prospected.
2020, 40(4): 873-885
doi: 10.6023/cjoc201911009
Abstract:
Organosilicon compounds have been widely used in organic synthesis, biomedicine, material science and other fields. The development of simple and efficient C——Si bond construction methodology has attracted extensive attention from scientists. Transition-metal-catalyzed carbene insertion reaction of Si——H bond is one of the important methods to form C——Si bond. It not only has the advantages of simple operation, mild reaction conditions and high atom economy, but also can be used to synthesize various chiral organosilanes with high enantioselectivity through the regulation of chiral ligands. In recent years, achieved rapid development has been in this field, and various new carbene precursors and metal catalytic systems have been emerged. According to the group of transition metal elements, recent advance in the iron, copper, zinc, ruthenium, rhodium, palladium, silver, iridium and gold catalyzed carbene insertion reactions of Si——H bond since 2012 is reviewed in five parts.
Organosilicon compounds have been widely used in organic synthesis, biomedicine, material science and other fields. The development of simple and efficient C——Si bond construction methodology has attracted extensive attention from scientists. Transition-metal-catalyzed carbene insertion reaction of Si——H bond is one of the important methods to form C——Si bond. It not only has the advantages of simple operation, mild reaction conditions and high atom economy, but also can be used to synthesize various chiral organosilanes with high enantioselectivity through the regulation of chiral ligands. In recent years, achieved rapid development has been in this field, and various new carbene precursors and metal catalytic systems have been emerged. According to the group of transition metal elements, recent advance in the iron, copper, zinc, ruthenium, rhodium, palladium, silver, iridium and gold catalyzed carbene insertion reactions of Si——H bond since 2012 is reviewed in five parts.
2020, 40(4): 886-898
doi: 10.6023/cjoc201910020
Abstract:
Recently, the direct sulfenylation of C——H bond for C——S formation under transition metal-free conditions has rapidly advanced and is employed for eco-friendly synthesis of sulfenylated natural or bioactive compounds with various sulfenylating reagents. In particular, the sulfenylation of indoles is considered to be the most important because it can lead to a new class of molecules displaying a broad spectrum of biological and pharmaceutical activities. The recent five-year progress in direct C——H bond sulfenylation of indoles under transition metal-free conditions is discussed and their mechanisms in detail are described.
Recently, the direct sulfenylation of C——H bond for C——S formation under transition metal-free conditions has rapidly advanced and is employed for eco-friendly synthesis of sulfenylated natural or bioactive compounds with various sulfenylating reagents. In particular, the sulfenylation of indoles is considered to be the most important because it can lead to a new class of molecules displaying a broad spectrum of biological and pharmaceutical activities. The recent five-year progress in direct C——H bond sulfenylation of indoles under transition metal-free conditions is discussed and their mechanisms in detail are described.
2020, 40(4): 899-912
doi: 10.6023/cjoc201909035
Abstract:
The synthesis of alkyl boronic esters has attracted much attention because of their wide applications in organic synthesis, materials and medicines. Transition-metal catalyzed hydroboration of alkenes was one of the most effective methods to construct alkyl boronic esters. Compared with rhodium, ruthenium, palladium, iridium and other precious metal catalysts, iron, cobalt and nickel catalysts were not only low cost, but also they displayed unique reactivity and selectivity. In this paper, the important advances in hydroboration of alkenes catalyzed by iron, cobalt and nickel have been summarized since 1994, including catalytic activity, selectivity and substrate scope of different catalytic systems.
The synthesis of alkyl boronic esters has attracted much attention because of their wide applications in organic synthesis, materials and medicines. Transition-metal catalyzed hydroboration of alkenes was one of the most effective methods to construct alkyl boronic esters. Compared with rhodium, ruthenium, palladium, iridium and other precious metal catalysts, iron, cobalt and nickel catalysts were not only low cost, but also they displayed unique reactivity and selectivity. In this paper, the important advances in hydroboration of alkenes catalyzed by iron, cobalt and nickel have been summarized since 1994, including catalytic activity, selectivity and substrate scope of different catalytic systems.
2020, 40(4): 913-921
doi: 10.6023/cjoc202002040
Abstract:
In this paper, a new peroxide-induced carbon-centered radical relay carbocyclization reaction with 2-arylbenzo-imidazoles is described. This method provides an efficient route to a series of structurally diverse benzimidazole[2, 1-a]iso-quinolines under mild conditions in a straightforward manner. The reaction is compatible with a wide substrate scope, excellent functional group tolerance and high step economy. Mechanistic studies suggest that the reaction proceeds through a carbon-centered radical pathway.
In this paper, a new peroxide-induced carbon-centered radical relay carbocyclization reaction with 2-arylbenzo-imidazoles is described. This method provides an efficient route to a series of structurally diverse benzimidazole[2, 1-a]iso-quinolines under mild conditions in a straightforward manner. The reaction is compatible with a wide substrate scope, excellent functional group tolerance and high step economy. Mechanistic studies suggest that the reaction proceeds through a carbon-centered radical pathway.
2020, 40(4): 922-929
doi: 10.6023/cjoc201910011
Abstract:
The Lewis acid catalyzed 1, 2-addition reaction of trifluoromethylated acylhydrazones with trimethylsilyl cyanide was investigated, and a series of cyanohydrazide compounds containing trifluoromethyl group were afforded in high yield. The method could be easily operated in mild reaction conditions, which provides an efficient method for the synthesis of trifluoromethylated hydrazides with structural diversity.
The Lewis acid catalyzed 1, 2-addition reaction of trifluoromethylated acylhydrazones with trimethylsilyl cyanide was investigated, and a series of cyanohydrazide compounds containing trifluoromethyl group were afforded in high yield. The method could be easily operated in mild reaction conditions, which provides an efficient method for the synthesis of trifluoromethylated hydrazides with structural diversity.
2020, 40(4): 930-937
doi: 10.6023/cjoc201910014
Abstract:
α, α, γ, γ-Tetrafluoro-β-hydroxy ketones and α-fluoroacetophenones are widely used in the fields of organic chemistry, agrochemicals, and pharmaceuticals. A mild and excellent method to synthesize α, α, γ, γ-tetrafluoro-β-hydroxy ketones and α-fluoroacetophenones via various 1, 3-diaryl-1, 3-diketones has been developed. With the modification of reaction conditions, two different products could be obtained in moderate to good yields, respectively.
α, α, γ, γ-Tetrafluoro-β-hydroxy ketones and α-fluoroacetophenones are widely used in the fields of organic chemistry, agrochemicals, and pharmaceuticals. A mild and excellent method to synthesize α, α, γ, γ-tetrafluoro-β-hydroxy ketones and α-fluoroacetophenones via various 1, 3-diaryl-1, 3-diketones has been developed. With the modification of reaction conditions, two different products could be obtained in moderate to good yields, respectively.
2020, 40(4): 938-943
doi: 10.6023/cjoc201908003
Abstract:
Polysuccinimide (PSI) was synthesized by thermal condensation of L-aspartic acid as raw materials and phosphoric acid (85% by volume) as catalyst. The water-soluble polyaspartamide fluorescent probes (SD-PHEA-RhB) was further synthesized by ring-opening reaction between PSI with the amino groups of ethanolamine and rhodamine B (RhB) modified by ethylenediamine, and then nucleophilic substitution reaction of sulfadiazine (SD). SD-PHEA-RhB was characterized by 1H NMR, IR, UV, gel permeation chromatograph (GPC), mass spectrometry and so on. Its molecular weight and distribution, particle size, fluorescence properties, in vitro cell cytotoxicity, cellular uptake and fluorescent imaging assays were also measured. Experimental data showed that the fluorescent probe possessed good water solubility and high sensitive to the acidic conditions. Moreover, these fluorescent probes had low in vitro cytotoxicities to HepG2 and HeLa cells, high specific uptake and good red fluorescent imaging in HeLa tumor cells.
Polysuccinimide (PSI) was synthesized by thermal condensation of L-aspartic acid as raw materials and phosphoric acid (85% by volume) as catalyst. The water-soluble polyaspartamide fluorescent probes (SD-PHEA-RhB) was further synthesized by ring-opening reaction between PSI with the amino groups of ethanolamine and rhodamine B (RhB) modified by ethylenediamine, and then nucleophilic substitution reaction of sulfadiazine (SD). SD-PHEA-RhB was characterized by 1H NMR, IR, UV, gel permeation chromatograph (GPC), mass spectrometry and so on. Its molecular weight and distribution, particle size, fluorescence properties, in vitro cell cytotoxicity, cellular uptake and fluorescent imaging assays were also measured. Experimental data showed that the fluorescent probe possessed good water solubility and high sensitive to the acidic conditions. Moreover, these fluorescent probes had low in vitro cytotoxicities to HepG2 and HeLa cells, high specific uptake and good red fluorescent imaging in HeLa tumor cells.
2020, 40(4): 950-958
doi: 10.6023/cjoc201909040
Abstract:
Starting from 2-aminonaphthalene-1, 4-dione and o-dibromoarene, palladium-catalyzed one-pot synthesis of carbazolequinone was examined in detail. With PdCl2 as the catalyst, 2-dicyclohexylphosphino-2', 4', 6'-triisopropylbiphenyl (Xphos) as ligand and K2CO3 as base in N, N-dimethylformamide (DMF) at 160℃ for 72 h, the annulation reaction afforded the corresponding product by N-H/C-H double arylation process in 81% yield. With different o-dihaloarenes, a series of carbazolequinone derivatives were synthesized to examine the scope and limitation of the above method, and the structure of products was characterized by 1H NMR and 13C NMR spectra.
Starting from 2-aminonaphthalene-1, 4-dione and o-dibromoarene, palladium-catalyzed one-pot synthesis of carbazolequinone was examined in detail. With PdCl2 as the catalyst, 2-dicyclohexylphosphino-2', 4', 6'-triisopropylbiphenyl (Xphos) as ligand and K2CO3 as base in N, N-dimethylformamide (DMF) at 160℃ for 72 h, the annulation reaction afforded the corresponding product by N-H/C-H double arylation process in 81% yield. With different o-dihaloarenes, a series of carbazolequinone derivatives were synthesized to examine the scope and limitation of the above method, and the structure of products was characterized by 1H NMR and 13C NMR spectra.
2020, 40(4): 959-968
doi: 10.6023/cjoc201909017
Abstract:
Novel nitrogen-containing heterocyclic scaffold pyridazino[6, 1-b]quinazolinones were designed by the combination of two privileged structure units. Then a scheme for the synthesis of pyridazino[6, 1-b]quinazolinone derivatives in 4 steps starting from methyl 2-aminobenzoate was developed in which the intramolecular condensation of acylhydrazone with ester was a key step transformation. 14 pyridazino[6, 1-b]quinazolinone derivatives were synthesized and their structures were characterized and comfirmed by 1H NMR, 13C NMR and HRMS. Their in vitro cytotoxic activities against a panel of human tumor cell lines (SK-OV-3, CNE-2, MGC-803, NCI-H460) and nomal liver cell LO2 were evaluated via methyl thiazolyl tetrazolium (MTT) assay. The result indicated that 2-(4-bromophenyl)-4-hydroxy-10H-pyridazino[6, 1-b]quinazolin-10-one (4b) and 2-(3-chlorophenyl)-4-hydroxy-10H-pyridazino[6, 1-b]quinazolin-10-one (4d) exhibted very potent cytotoxic activity. The IC50value of 4b against CNE-2 and 4d against NCI-H460 cell line lowed to 0.85 and 2.31 μmol/L, respectively, far potent than the positive control cisplatin and almost equivalent to the natrual anticancer medicine camptothecin. Ultraviolet spectrometry and fluorescence titration assay were carried out to evaluate the ability of the compound to interact with DNA. The result indicated that they were able to intercalate in to DNA. Compound 4d, which demonstrated potent antitumor activity while less cytotoxicity against the normal liver cell LO2, could arrest cell cycle at G1 phase and significantly induce apoptosis on NCI-H460 cell in a dose-dependent manner, while 4b which exhibit potent cytotoxicity against LO2, could result in significant DNA double strand break when treated with the cell.
Novel nitrogen-containing heterocyclic scaffold pyridazino[6, 1-b]quinazolinones were designed by the combination of two privileged structure units. Then a scheme for the synthesis of pyridazino[6, 1-b]quinazolinone derivatives in 4 steps starting from methyl 2-aminobenzoate was developed in which the intramolecular condensation of acylhydrazone with ester was a key step transformation. 14 pyridazino[6, 1-b]quinazolinone derivatives were synthesized and their structures were characterized and comfirmed by 1H NMR, 13C NMR and HRMS. Their in vitro cytotoxic activities against a panel of human tumor cell lines (SK-OV-3, CNE-2, MGC-803, NCI-H460) and nomal liver cell LO2 were evaluated via methyl thiazolyl tetrazolium (MTT) assay. The result indicated that 2-(4-bromophenyl)-4-hydroxy-10H-pyridazino[6, 1-b]quinazolin-10-one (4b) and 2-(3-chlorophenyl)-4-hydroxy-10H-pyridazino[6, 1-b]quinazolin-10-one (4d) exhibted very potent cytotoxic activity. The IC50value of 4b against CNE-2 and 4d against NCI-H460 cell line lowed to 0.85 and 2.31 μmol/L, respectively, far potent than the positive control cisplatin and almost equivalent to the natrual anticancer medicine camptothecin. Ultraviolet spectrometry and fluorescence titration assay were carried out to evaluate the ability of the compound to interact with DNA. The result indicated that they were able to intercalate in to DNA. Compound 4d, which demonstrated potent antitumor activity while less cytotoxicity against the normal liver cell LO2, could arrest cell cycle at G1 phase and significantly induce apoptosis on NCI-H460 cell in a dose-dependent manner, while 4b which exhibit potent cytotoxicity against LO2, could result in significant DNA double strand break when treated with the cell.
2020, 40(4): 969-977
doi: 10.6023/cjoc201909006
Abstract:
A novel air-stable β-naphthol formaldehyde Schiff base zirconium perfluorooctanesulfonate Lewis acid catalyst was successfully synthesized by the reaction of β-naphthol formaldehyde Schiff base zirconium dichlorides with silver perfluorooctanesulfonate in the absence of light at room temperature. The results of catalytic assessment showed that this complex (5 mol%) could effectively catalyze the Hantzsch reaction of aldehydes, β-keto ester and ammonium acetate to obtain 1, 4-dihydropyridine compounds at 80℃ under solvent-free conditions in good to excellent yields. Meanwhile, it could also effectively catalyze the reaction of aromatic aldehydes, cyclic β-diketone, β-keto ester and ammonium acetate to obtain 4-aryl polyhydroquinoline compounds. This catalyst could be reused 5 times, and the yields had no significant decrease. This procedure provides a simple and efficient way for the synthesis of 1, 4-dihydropyridine and polyhydroquinoline compounds.
A novel air-stable β-naphthol formaldehyde Schiff base zirconium perfluorooctanesulfonate Lewis acid catalyst was successfully synthesized by the reaction of β-naphthol formaldehyde Schiff base zirconium dichlorides with silver perfluorooctanesulfonate in the absence of light at room temperature. The results of catalytic assessment showed that this complex (5 mol%) could effectively catalyze the Hantzsch reaction of aldehydes, β-keto ester and ammonium acetate to obtain 1, 4-dihydropyridine compounds at 80℃ under solvent-free conditions in good to excellent yields. Meanwhile, it could also effectively catalyze the reaction of aromatic aldehydes, cyclic β-diketone, β-keto ester and ammonium acetate to obtain 4-aryl polyhydroquinoline compounds. This catalyst could be reused 5 times, and the yields had no significant decrease. This procedure provides a simple and efficient way for the synthesis of 1, 4-dihydropyridine and polyhydroquinoline compounds.
2020, 40(4): 944-949
doi: 10.6023/cjoc201911014
Abstract:
A heteroditopic monomer (H) comprised of ureidopyrimidinone (UPy) group and benzo-21-crown-7 motif and a homoditopic monomer (G) containing two dialkylammonium salt units have been successfully prepared. The functional groups both in H and G are linked together by a short spacer. Through quadruple hydrogen bonds, H can self-assemble into dimers, which are capable of complexing with G via host-guest interaction to form linear supramolecular copolymers. The supramolecular copolymers were fully characterized by various techniques, such as concentration-dependent 1H NMR, viscosity measurements, and scanning electron microscope (SEM). The results will inspire the orthogonal construction of supramolecular polymers for smart materials in more fields.
A heteroditopic monomer (H) comprised of ureidopyrimidinone (UPy) group and benzo-21-crown-7 motif and a homoditopic monomer (G) containing two dialkylammonium salt units have been successfully prepared. The functional groups both in H and G are linked together by a short spacer. Through quadruple hydrogen bonds, H can self-assemble into dimers, which are capable of complexing with G via host-guest interaction to form linear supramolecular copolymers. The supramolecular copolymers were fully characterized by various techniques, such as concentration-dependent 1H NMR, viscosity measurements, and scanning electron microscope (SEM). The results will inspire the orthogonal construction of supramolecular polymers for smart materials in more fields.
2020, 40(4): 978-987
doi: 10.6023/cjoc201909016
Abstract:
With the expectation to find out novel and effective anti-tumor agents, a series of novel trimethoxyphenyl-quinoline hybrids were designed, synthesized and evaluated for antiproliferative activity against three human cancer cell lines (EC-109, human esophageal cancer cells; PC-3, human prostate cancer cells; MGC-803, human gastric cancer cells). N-(3-(Chloromethyl)benzyl)-3, 4, 5-trimethoxy-N-(quinolin-8-yl)benzamide (12j) showed the most potent antitumor activity against PC-3 cells with IC50 value of 9.23 μmol/L. Meanwhile, compound 12j inhibited the cell viability and colony formation of PC-3 cells. Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.
With the expectation to find out novel and effective anti-tumor agents, a series of novel trimethoxyphenyl-quinoline hybrids were designed, synthesized and evaluated for antiproliferative activity against three human cancer cell lines (EC-109, human esophageal cancer cells; PC-3, human prostate cancer cells; MGC-803, human gastric cancer cells). N-(3-(Chloromethyl)benzyl)-3, 4, 5-trimethoxy-N-(quinolin-8-yl)benzamide (12j) showed the most potent antitumor activity against PC-3 cells with IC50 value of 9.23 μmol/L. Meanwhile, compound 12j inhibited the cell viability and colony formation of PC-3 cells. Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.
2020, 40(4): 988-996
doi: 10.6023/cjoc201908029
Abstract:
A series of Schiff base catalysts (4) derived from Tröger's base-NH2 were synthesized and used to promote the multi-component reactions of substituted salicylaldehydes, malononitrile and substituted 2-mercaptoimidazole to afford 5-(1H-imidazol-2-ylthio)-2, 4-diamino-5H-chromeno[2, 3-b]pyridine-3-carbonitrile derivatives (8) efficiently. The reaction mechanism was discussed based on the 1H NMR analysis preliminarily. Most of products showed high inhibitory on the human breast adenocarcinoma cell (MCF-7) and adenocarcinomic human alveolarbasal epithelial cell (A549). 5-(1H-Imidazol-2-ylthio)-2, 4-diamino-7-fluoro-5H-chromeno[2, 3-b]pyridine-3-carbonitrile has antibacterial activity against Staphylococcus aureus (wild type) and Escherichia coli (wild type). The results expanded the application of Tröger's bases in organocatalysis and showed the potential of products in new drug development.
A series of Schiff base catalysts (4) derived from Tröger's base-NH2 were synthesized and used to promote the multi-component reactions of substituted salicylaldehydes, malononitrile and substituted 2-mercaptoimidazole to afford 5-(1H-imidazol-2-ylthio)-2, 4-diamino-5H-chromeno[2, 3-b]pyridine-3-carbonitrile derivatives (8) efficiently. The reaction mechanism was discussed based on the 1H NMR analysis preliminarily. Most of products showed high inhibitory on the human breast adenocarcinoma cell (MCF-7) and adenocarcinomic human alveolarbasal epithelial cell (A549). 5-(1H-Imidazol-2-ylthio)-2, 4-diamino-7-fluoro-5H-chromeno[2, 3-b]pyridine-3-carbonitrile has antibacterial activity against Staphylococcus aureus (wild type) and Escherichia coli (wild type). The results expanded the application of Tröger's bases in organocatalysis and showed the potential of products in new drug development.
2020, 40(4): 997-1002
doi: 10.6023/cjoc201910032
Abstract:
A new chiral tridentate PNN ligand, indan-f-amphox (a sister ligand of f-amphox), was synthesized and applied in iridium-catalyzed asymmetric hydrogenation of β-aryl β-ketoesters. A wide range of β-aryl β-ketoesters are reduced using an Ir(Ⅲ)-indan-f-amphox catalyst with excellent enantioselectivities and reactivities (up to 99% ee, TON=10000).
A new chiral tridentate PNN ligand, indan-f-amphox (a sister ligand of f-amphox), was synthesized and applied in iridium-catalyzed asymmetric hydrogenation of β-aryl β-ketoesters. A wide range of β-aryl β-ketoesters are reduced using an Ir(Ⅲ)-indan-f-amphox catalyst with excellent enantioselectivities and reactivities (up to 99% ee, TON=10000).
2020, 40(4): 1003-1016
doi: 10.6023/cjoc201910016
Abstract:
The triethylamine promoted cycloaddition reaction of N-phenacylquinolinium bromide with 1, 3-indanedione gave functionalized dihydropyrrolo[1, 2-a]quinolines as main products and 2-(1-(2-oxo-2-phenylethyl)-quinolin-4-ylidene)-indene-1, 3-diones as minor products. The similar reaction with N-benzylquinolinium bromide gave 2-(1-(2-oxo-2-phenylethyl)-quino-lin-4-ylidene)-indene-1, 3-diones as major products. On the other hand, triethylamine promoted three-component reaction of N-phenacyl, N-ethoxycarbonylmethyl and N-(4-nitrobenzyl)quinolinium salts, aromatic aldehydes and 1, 3-indanedione in ethanol at room temperature afforded functionalized spiro[indene-2, 3'-pyrrolo[1, 2-a]quinolone]s in good yields and with high diastereoselectivity.
The triethylamine promoted cycloaddition reaction of N-phenacylquinolinium bromide with 1, 3-indanedione gave functionalized dihydropyrrolo[1, 2-a]quinolines as main products and 2-(1-(2-oxo-2-phenylethyl)-quinolin-4-ylidene)-indene-1, 3-diones as minor products. The similar reaction with N-benzylquinolinium bromide gave 2-(1-(2-oxo-2-phenylethyl)-quino-lin-4-ylidene)-indene-1, 3-diones as major products. On the other hand, triethylamine promoted three-component reaction of N-phenacyl, N-ethoxycarbonylmethyl and N-(4-nitrobenzyl)quinolinium salts, aromatic aldehydes and 1, 3-indanedione in ethanol at room temperature afforded functionalized spiro[indene-2, 3'-pyrrolo[1, 2-a]quinolone]s in good yields and with high diastereoselectivity.
2020, 40(4): 1017-1027
doi: 10.6023/cjoc201909026
Abstract:
1, 7-Bis(N-substituted-aminomethyl)-2, 8-dihydroxy-Tröger's bases (4) were synthesized and used as efficient organocatalyst for the Aldol reaction of 4-hydroxylcoumarin and 2-benzylidenemalononitrile (or methyl(ethyl)-2-cyano-3-phenylacrylate) to afford 2-amino-4-aryl-5-oxo-4H, 5H-pyrano[3, 2-c]chromene-3-carbonitriles (carboxylates) (8). Subse-quently, they were used as the efficient ligand to promote the Pd-catalyzed Aldol-Ullmann reaction to give 7-aryl-7, 12-dihydro-6H-chromeno[3', 4':5, 6]pyrano[2, 3-b]indol-6-one (10) and 5'(or 5', 7')-substituted-6H, 12H-spiro[chromeno[3', 4':5, 6]-pyrano[2, 3-b]indole-7, 3'-indoline]-2', 6-dione (12), respectively. The anti-cancer activity on human three positive breast cancer cells (MCF-7), human three negative breast cancer cells (MDA-MB-231), human hepatoma cells (HepG2), human hepatoma cells (MHCC-97H) and cytotoxicity on human hepatocyte cells (LO2) of catalyst 4 and all products in vitro were evaluated. 1, 7-Bis((methylamino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazocine-2, 8-diol (4b) had selective inhibition (inhi-bition rate>30%) on MCF-7 cells while 1, 7-bis(((1-phenylethyl)amino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazo-cine-2, 8-diol (4d) and 1, 7-bis(((pyridin-2-ylmethyl)amino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazocine-2, 8-diol (4e) had selective inhibition on MDA-MB-231 cells. 2-Amino-5-oxo-4-(3, 4, 5-trimethoxyphenyl)-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8q) had strong inhibitory effects on three kinds of cancer cells except MDA-MB-231 while 2-amino-4-(4-bromophenyl)-5-oxo-4H, 5H-pyrano[3, 2-c]chromene-3-carbonitrile (8a), 2-amino-4-(2, 4-dichlorophenyl)-5-oxo-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8e), 2-amino-4-(3-fluorophenyl)-5-oxo-4H, 5H-pyrano[3, 2-c]chrome-ne-3-carbonitrile (8m) and 2-amino-4-(3-bromophenyl)-5-oxo-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8n) had strong inhibitory effects on four kinds of cancer cells. However, all the compounds showed cytotoxicity to normal LO2 cells which prompts the necessary of structure modification to reduce the toxicity.
1, 7-Bis(N-substituted-aminomethyl)-2, 8-dihydroxy-Tröger's bases (4) were synthesized and used as efficient organocatalyst for the Aldol reaction of 4-hydroxylcoumarin and 2-benzylidenemalononitrile (or methyl(ethyl)-2-cyano-3-phenylacrylate) to afford 2-amino-4-aryl-5-oxo-4H, 5H-pyrano[3, 2-c]chromene-3-carbonitriles (carboxylates) (8). Subse-quently, they were used as the efficient ligand to promote the Pd-catalyzed Aldol-Ullmann reaction to give 7-aryl-7, 12-dihydro-6H-chromeno[3', 4':5, 6]pyrano[2, 3-b]indol-6-one (10) and 5'(or 5', 7')-substituted-6H, 12H-spiro[chromeno[3', 4':5, 6]-pyrano[2, 3-b]indole-7, 3'-indoline]-2', 6-dione (12), respectively. The anti-cancer activity on human three positive breast cancer cells (MCF-7), human three negative breast cancer cells (MDA-MB-231), human hepatoma cells (HepG2), human hepatoma cells (MHCC-97H) and cytotoxicity on human hepatocyte cells (LO2) of catalyst 4 and all products in vitro were evaluated. 1, 7-Bis((methylamino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazocine-2, 8-diol (4b) had selective inhibition (inhi-bition rate>30%) on MCF-7 cells while 1, 7-bis(((1-phenylethyl)amino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazo-cine-2, 8-diol (4d) and 1, 7-bis(((pyridin-2-ylmethyl)amino)methyl)-6H, 12H-5, 11-methanodibenzo[b, f] [1, 5]diazocine-2, 8-diol (4e) had selective inhibition on MDA-MB-231 cells. 2-Amino-5-oxo-4-(3, 4, 5-trimethoxyphenyl)-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8q) had strong inhibitory effects on three kinds of cancer cells except MDA-MB-231 while 2-amino-4-(4-bromophenyl)-5-oxo-4H, 5H-pyrano[3, 2-c]chromene-3-carbonitrile (8a), 2-amino-4-(2, 4-dichlorophenyl)-5-oxo-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8e), 2-amino-4-(3-fluorophenyl)-5-oxo-4H, 5H-pyrano[3, 2-c]chrome-ne-3-carbonitrile (8m) and 2-amino-4-(3-bromophenyl)-5-oxo-4H, 5H-dihydropyrano[3, 2-c]chromene-3-carbonitrile (8n) had strong inhibitory effects on four kinds of cancer cells. However, all the compounds showed cytotoxicity to normal LO2 cells which prompts the necessary of structure modification to reduce the toxicity.
2020, 40(4): 1028-1032
doi: 10.6023/cjoc201911026
Abstract:
As aryl triflates are widely used in organic synthesis and medicinal chemistry, significant efforts have been directed towards the development of efficient methods for their synthesis. It was found that trifluoromethanesulfonyl pyridinium salt (C5H5N+SO2CF3·CF3SO3-) was able to act as a mild trifluoromethanesulfonylation reagent to convert phenols into aryl triflates. All aryl triflate products could be purified simply by washing, and tedious chromatography operations were avoided. Besides aryl triflates, vinyl triflates could also be synthesized by using this pyridinium salt as reagent. The pyridinium salt could be easily prepared and purified, is stable under dry atmosphere, and thus may become an easy-to-handle reagent.
As aryl triflates are widely used in organic synthesis and medicinal chemistry, significant efforts have been directed towards the development of efficient methods for their synthesis. It was found that trifluoromethanesulfonyl pyridinium salt (C5H5N+SO2CF3·CF3SO3-) was able to act as a mild trifluoromethanesulfonylation reagent to convert phenols into aryl triflates. All aryl triflate products could be purified simply by washing, and tedious chromatography operations were avoided. Besides aryl triflates, vinyl triflates could also be synthesized by using this pyridinium salt as reagent. The pyridinium salt could be easily prepared and purified, is stable under dry atmosphere, and thus may become an easy-to-handle reagent.
2020, 40(4): 1068-1073
doi: 10.6023/cjoc201908031
Abstract:
Coumarin and thiazole are two classes of important heterocycles with many biological activities and pharmacological effects. It is very meaningful to synthesize thiazolyl coumarin derivatives in medicinal chemistry area. In this study, a facile and efficient one-pot process was developed to synthesize substituted aminothiazoles from 3-acetylcoumarins and thiourea/N-substituted thioureas under the media of I2/CuO. All target molecules were characterized by NMR, IR spectra and MS.
Coumarin and thiazole are two classes of important heterocycles with many biological activities and pharmacological effects. It is very meaningful to synthesize thiazolyl coumarin derivatives in medicinal chemistry area. In this study, a facile and efficient one-pot process was developed to synthesize substituted aminothiazoles from 3-acetylcoumarins and thiourea/N-substituted thioureas under the media of I2/CuO. All target molecules were characterized by NMR, IR spectra and MS.
2020, 40(4): 1033-1037
doi: 10.6023/cjoc201909027
Abstract:
A new method for the iodocyclization of olefinic dicarbonyl compounds with t-butyl hydroperoxide (TBHP) and I2 was developed. The in situ generated hypoiodous acid and tBuOI were used as active iodine cation reagents. This method allowed the synthesis of polysubstituted 5-iodomethyldihydrofurans under mild reaction conditions with cheap reagents and high atom economy.
A new method for the iodocyclization of olefinic dicarbonyl compounds with t-butyl hydroperoxide (TBHP) and I2 was developed. The in situ generated hypoiodous acid and tBuOI were used as active iodine cation reagents. This method allowed the synthesis of polysubstituted 5-iodomethyldihydrofurans under mild reaction conditions with cheap reagents and high atom economy.
2020, 40(4): 1038-1042
doi: 10.6023/cjoc201908033
Abstract:
Two new ortho-dialkyl-substituted aromatic acids 1 and 2 were isolated from Verrucosispora sp. NS0172. The chemical structures of 1 and 2 were determined by spectroscopic methods including 1D- and 2D-NMR and HR-ESIMS experiments. The cytotoxicity of compounds 1 and 2 was evaluated by methyl thiazolyl tetrazolium (MTT) assay, and compound 1 showed potent antiproliferative activity against human hepatocellular carcinoma SMMC-7721 (IC50 7.74 μmol·L-1). Compounds 1 and 2 were tested for the antimicrobial and antifungal activities by filter paper disc diffusion assay, and both of them showed no evident activities at a dose of 40 μg/disc. This study is the first report of discovering of ortho-dialkyl-substi-tuted aromatic acids from Verrucosispora, which sets the foundation for future biosynthetic study of this class of natural products in Verrucosispora.
Two new ortho-dialkyl-substituted aromatic acids 1 and 2 were isolated from Verrucosispora sp. NS0172. The chemical structures of 1 and 2 were determined by spectroscopic methods including 1D- and 2D-NMR and HR-ESIMS experiments. The cytotoxicity of compounds 1 and 2 was evaluated by methyl thiazolyl tetrazolium (MTT) assay, and compound 1 showed potent antiproliferative activity against human hepatocellular carcinoma SMMC-7721 (IC50 7.74 μmol·L-1). Compounds 1 and 2 were tested for the antimicrobial and antifungal activities by filter paper disc diffusion assay, and both of them showed no evident activities at a dose of 40 μg/disc. This study is the first report of discovering of ortho-dialkyl-substi-tuted aromatic acids from Verrucosispora, which sets the foundation for future biosynthetic study of this class of natural products in Verrucosispora.
2020, 40(4): 1043-1049
doi: 10.6023/cjoc201910024
Abstract:
Hydrogen sulfide (H2S) and pH play a most important role in vivo and environment. A fluorescent probe for fast and sensitive detection of H2S and pH are of vital importance for research their functions. A naphthalimide-based fluorescent probe L has been designed and synthesized based on intramolecular charge transfer (ICT) mechanism by utilizing azide as recognition site. The probe L has demonstrated good stability in the pH range of 4~11. It showed satisfactory sensitivity and rapidly response (less than 3 min) to H2S. An excellent linear relationship (R2=0.99823) displayed in the range of H2S concentrations from 0 μmol·L-1 to 20 μmol·L-1 and the detection limit was 1.18 μmol·L-1. Furthermore, in the present 30 equiv. H2S, it was successfully applied to detection of pH with good linear relationship (R2=0.98764) in the pH range of 2~6.5. This methods provide a reference for detection of H2S and pH value in the presence of 30 equiv. H2S, which have potential application prospects in analytical detection and pathological analysis.
Hydrogen sulfide (H2S) and pH play a most important role in vivo and environment. A fluorescent probe for fast and sensitive detection of H2S and pH are of vital importance for research their functions. A naphthalimide-based fluorescent probe L has been designed and synthesized based on intramolecular charge transfer (ICT) mechanism by utilizing azide as recognition site. The probe L has demonstrated good stability in the pH range of 4~11. It showed satisfactory sensitivity and rapidly response (less than 3 min) to H2S. An excellent linear relationship (R2=0.99823) displayed in the range of H2S concentrations from 0 μmol·L-1 to 20 μmol·L-1 and the detection limit was 1.18 μmol·L-1. Furthermore, in the present 30 equiv. H2S, it was successfully applied to detection of pH with good linear relationship (R2=0.98764) in the pH range of 2~6.5. This methods provide a reference for detection of H2S and pH value in the presence of 30 equiv. H2S, which have potential application prospects in analytical detection and pathological analysis.
2020, 40(4): 1050-1054
doi: 10.6023/cjoc201908005
Abstract:
An efficient method for the preparation of 1, 3, 4-thiadiazine derivatives has been reported. With 2, 5-dihydroxy-1, 4-dithiane and α-chloroindole containing different substituents, 13 compounds were synthesized. The yields of the compounds were above 82% except (E)-4-phenyl-2-styryl-5, 6-dihydro-4H-1, 3, 4-thiadiazin-5-ol (3m). Furthermore, the proposed reaction mechanism was discussed. The developed method features simple operation, mild reaction condition, environmentally friendly, high yield and a broad range of substrate applicability. It provides a new way for the synthesis of 1, 3, 4-thiadiazine derivatives.
An efficient method for the preparation of 1, 3, 4-thiadiazine derivatives has been reported. With 2, 5-dihydroxy-1, 4-dithiane and α-chloroindole containing different substituents, 13 compounds were synthesized. The yields of the compounds were above 82% except (E)-4-phenyl-2-styryl-5, 6-dihydro-4H-1, 3, 4-thiadiazin-5-ol (3m). Furthermore, the proposed reaction mechanism was discussed. The developed method features simple operation, mild reaction condition, environmentally friendly, high yield and a broad range of substrate applicability. It provides a new way for the synthesis of 1, 3, 4-thiadiazine derivatives.
2020, 40(4): 1055-1061
doi: 10.6023/cjoc201910023
Abstract:
In order to find novel drug leads, a series of natural stilbene-inspired substituted styrylthiazole derivatives were designed and synthesized by hybridization of the structures of both bioactive 2, 6-difluorophenylthiazole moiety and stilbene. The structures of the title compounds were confirmed by 1H NMR, 13C NMR and ESI-HRMS. The in vitro antifungal bioassay results indicated that some compounds showed moderate inhibition activity against FusaHum graminearum, Helminthosporium maydis and Mycosphaerella melonis at 100 μg/mL, and the inhibition rate of (E)-5-bromo-4-(2, 6-difluorophenyl)-2-(4-tri-fluoromethylstyryl)thiazole (6p) against FusaHum graminearum reached 86.7%. These compounds were also screened for their topoisomerase I inhibitory activity using Top1-mediated relaxation assay. The results showed that all of them exhibited certain Top1 inhibitory activity at 50 μmol·L-1, and amongst them (E)-5-bromo-4-(2, 6-difluorophenyl)-2-(2-chlorosty-ryl)thiazole (6k) displayed promising Top1 inhibitory activity, which still remained certain activity at 0.2 μmol·L-1.
In order to find novel drug leads, a series of natural stilbene-inspired substituted styrylthiazole derivatives were designed and synthesized by hybridization of the structures of both bioactive 2, 6-difluorophenylthiazole moiety and stilbene. The structures of the title compounds were confirmed by 1H NMR, 13C NMR and ESI-HRMS. The in vitro antifungal bioassay results indicated that some compounds showed moderate inhibition activity against FusaHum graminearum, Helminthosporium maydis and Mycosphaerella melonis at 100 μg/mL, and the inhibition rate of (E)-5-bromo-4-(2, 6-difluorophenyl)-2-(4-tri-fluoromethylstyryl)thiazole (6p) against FusaHum graminearum reached 86.7%. These compounds were also screened for their topoisomerase I inhibitory activity using Top1-mediated relaxation assay. The results showed that all of them exhibited certain Top1 inhibitory activity at 50 μmol·L-1, and amongst them (E)-5-bromo-4-(2, 6-difluorophenyl)-2-(2-chlorosty-ryl)thiazole (6k) displayed promising Top1 inhibitory activity, which still remained certain activity at 0.2 μmol·L-1.
2020, 40(4): 1062-1067
doi: 10.6023/cjoc201908014
Abstract:
A convenient method for the practical synthesis of resveratrol, piceatannol and pinosylvin is described. Resveratrol, pinosylvin and piceatannol can be achieved through a simultaneous demethylation and isomerization process from stilbenes with the aid of aluminum and iodine. The overall yields of the reaction were 68%, 78% and 56% (based on aromatic aldehyde). The solvent of the reaction can be reused after filtered. At the same time, quantum chemical calculations and control experiments show that iodine radical may be the key factor leading to cis-trans isomerization of double bond in the process of demethylation.
A convenient method for the practical synthesis of resveratrol, piceatannol and pinosylvin is described. Resveratrol, pinosylvin and piceatannol can be achieved through a simultaneous demethylation and isomerization process from stilbenes with the aid of aluminum and iodine. The overall yields of the reaction were 68%, 78% and 56% (based on aromatic aldehyde). The solvent of the reaction can be reused after filtered. At the same time, quantum chemical calculations and control experiments show that iodine radical may be the key factor leading to cis-trans isomerization of double bond in the process of demethylation.
2020, 40(4): 1074-1075
doi: 10.6023/cjoc202000016
Abstract:
2020, 40(4): 1076-1077
doi: 10.6023/cjoc202000017
Abstract:
2020, 40(4): 1078-1079
doi: 10.6023/cjoc202000018
Abstract:
2020, 40(4): 1080-1081
doi: 10.6023/cjoc202000019
Abstract:
2020, 40(4): 1082-1083
doi: 10.6023/cjoc202000020
Abstract:
2020, 40(4): 1084-1085
doi: 10.6023/cjoc202000021
Abstract:
