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2019 Volume 39 Issue 11
2019, 39(11): 2989-3012
doi: 10.6023/cjoc201904037
Abstract:
N-O bond cleavage is one of the most efficient and powerful strategies to introduce N-or O-functional groups into molecules in organic synthesis. Copper catalyst, as the abundant in earth and inexpensive advantages has been widely used to construct C-N and C-O bond. Furthermore, N-O bond cleavage has been successfully applied in the total synthesis of natural products and pharmaceuticals. The new development of copper-catalyzed N-O bond cleavage and its application in the total synthesis of natural products and pharmaceuticals in recent years have been summarized.
N-O bond cleavage is one of the most efficient and powerful strategies to introduce N-or O-functional groups into molecules in organic synthesis. Copper catalyst, as the abundant in earth and inexpensive advantages has been widely used to construct C-N and C-O bond. Furthermore, N-O bond cleavage has been successfully applied in the total synthesis of natural products and pharmaceuticals. The new development of copper-catalyzed N-O bond cleavage and its application in the total synthesis of natural products and pharmaceuticals in recent years have been summarized.
2019, 39(11): 3013-3025
doi: 10.6023/cjoc201904044
Abstract:
The α-diazocarbonyl compounds are easy to prepare and can be dediazonized to highly reactive carbene intermediates under thermolytic or photolytic conditions. Chemical bonds can be efficiently constructed by carbene mediated reactions, including the insertion reaction of carbene into N-H bonds which is an effective method for constructing C-N bonds. The α-diazocarbonyl compounds have received extensive application in organic synthesis and pharmaceutical synthesis. The research progress in the insertion reaction of α-diazocarbonyl compounds into N-H bonds under transition metal, organic small molecules, biomacromolecule or photolytic and thermolytic conditions is summarized, including the reaction mechanism and synthesis applications. Finally, the prospects of this reaction are also discussed.
The α-diazocarbonyl compounds are easy to prepare and can be dediazonized to highly reactive carbene intermediates under thermolytic or photolytic conditions. Chemical bonds can be efficiently constructed by carbene mediated reactions, including the insertion reaction of carbene into N-H bonds which is an effective method for constructing C-N bonds. The α-diazocarbonyl compounds have received extensive application in organic synthesis and pharmaceutical synthesis. The research progress in the insertion reaction of α-diazocarbonyl compounds into N-H bonds under transition metal, organic small molecules, biomacromolecule or photolytic and thermolytic conditions is summarized, including the reaction mechanism and synthesis applications. Finally, the prospects of this reaction are also discussed.
2019, 39(11): 3026-3039
doi: 10.6023/cjoc201907051
Abstract:
Copper-catalyzed Ullmann-type C-N coupling reaction is one of the most effective methods to construct the C-N bonds. Water, as green and clean solvent, has been successfully employed in various organic reactions. According to the structure of ligands, the progress of ligand-assisted copper-catalyzed C-N cross-coupling reaction in aqueous media or pure water is summarized comprehensively, and the ligands include diamines, hydrazides, phenanthrolines, carbohydrates, pyridine-N-oxides, quinolines, oximes and salen. In addition, ligand-free copper-catalyzed C-N coupling reactions in aquous media or pure water are also reviewed.
Copper-catalyzed Ullmann-type C-N coupling reaction is one of the most effective methods to construct the C-N bonds. Water, as green and clean solvent, has been successfully employed in various organic reactions. According to the structure of ligands, the progress of ligand-assisted copper-catalyzed C-N cross-coupling reaction in aqueous media or pure water is summarized comprehensively, and the ligands include diamines, hydrazides, phenanthrolines, carbohydrates, pyridine-N-oxides, quinolines, oximes and salen. In addition, ligand-free copper-catalyzed C-N coupling reactions in aquous media or pure water are also reviewed.
2019, 39(11): 3040-3050
doi: 10.6023/cjoc201904022
Abstract:
Visible-light-promoted organic synthesis is an important research hotspot and frontier in organic chemistry in recent years. Particularly, as a novel organic photosensitizer, 2, 4, 5, 6-tetrakis(carbazol-9-yl)-1, 3-dicyanobenzene (4CzIPN) has showed excellent catalytic performance in visible-light-induced radical reactions. The recent progress on the transition-metal-free photosynthesis under visible-light catalyzed by 4CzIPN is reviewed, and the application of 4CzIPN for photocatalytic organic transformations from different precursors (including silicon reagent, carboxylic acid and its derivatives, sulfur-containing reagent and fluorine reagent) is included.
Visible-light-promoted organic synthesis is an important research hotspot and frontier in organic chemistry in recent years. Particularly, as a novel organic photosensitizer, 2, 4, 5, 6-tetrakis(carbazol-9-yl)-1, 3-dicyanobenzene (4CzIPN) has showed excellent catalytic performance in visible-light-induced radical reactions. The recent progress on the transition-metal-free photosynthesis under visible-light catalyzed by 4CzIPN is reviewed, and the application of 4CzIPN for photocatalytic organic transformations from different precursors (including silicon reagent, carboxylic acid and its derivatives, sulfur-containing reagent and fluorine reagent) is included.
2019, 39(11): 3051-3064
doi: 10.6023/cjoc201905024
Abstract:
Adenosine triphosphate (ATP) is a high-energy phosphate compound commonly existing in various living cells, which plays important roles in the biological activities such as energy storage, cell respiration and enzyme catalytic reactions. Therefore, it is very crucial to ATP research in bio-organism. Fluorescence detection techniques has the advantages of convenient operation, good selectivity and high sensitivity, etc. In recent years, the design and synthesis of efficient ATP fluorescence sensors have become a research focus in the fields of biochemistry and analytical chemistry. According to the structure characteristics, ATP fluorescence chemosensors are categorized as Zn(Ⅱ) metal ions as recognition of bonding site type, other metal ions as recognition of bonding site type and electrostatic or hydrogen bond as interaction type. Based on organic small molecule fluorescence sensors, the recent progress in research of ATP fluorescence sensors in molecular design and application is reviewed, and the prospects for their development are discussed.
Adenosine triphosphate (ATP) is a high-energy phosphate compound commonly existing in various living cells, which plays important roles in the biological activities such as energy storage, cell respiration and enzyme catalytic reactions. Therefore, it is very crucial to ATP research in bio-organism. Fluorescence detection techniques has the advantages of convenient operation, good selectivity and high sensitivity, etc. In recent years, the design and synthesis of efficient ATP fluorescence sensors have become a research focus in the fields of biochemistry and analytical chemistry. According to the structure characteristics, ATP fluorescence chemosensors are categorized as Zn(Ⅱ) metal ions as recognition of bonding site type, other metal ions as recognition of bonding site type and electrostatic or hydrogen bond as interaction type. Based on organic small molecule fluorescence sensors, the recent progress in research of ATP fluorescence sensors in molecular design and application is reviewed, and the prospects for their development are discussed.
2019, 39(11): 3065-3083
doi: 10.6023/cjoc201905016
Abstract:
The cross dehydrogenation coupling reaction realizes direct coupling of two different X-H bonds to form a new chemical bond, thus featuring excellent step and atom economy. The traditional cross dehydrogenation coupling reaction was usually catalyzed by transition metal, which had the problems of expensive catalyst and serious pollution. Visible light-induced electron transfer is also an effective way to realize direct functionalization of X-H bonds. Visible-light-induced cross dehydrogenation coupling reaction under transition metal-free conditions is widely concerned due to the advantages of cleanliness, safety as well as high step and atom economy. Classified by the type of bonding, the research progress of these reactions is reviewed, and their future outlook is also discussed.
The cross dehydrogenation coupling reaction realizes direct coupling of two different X-H bonds to form a new chemical bond, thus featuring excellent step and atom economy. The traditional cross dehydrogenation coupling reaction was usually catalyzed by transition metal, which had the problems of expensive catalyst and serious pollution. Visible light-induced electron transfer is also an effective way to realize direct functionalization of X-H bonds. Visible-light-induced cross dehydrogenation coupling reaction under transition metal-free conditions is widely concerned due to the advantages of cleanliness, safety as well as high step and atom economy. Classified by the type of bonding, the research progress of these reactions is reviewed, and their future outlook is also discussed.
2019, 39(11): 3084-3104
doi: 10.6023/cjoc201905027
Abstract:
The C-H activation assisted by directing groups is an important measure for selective C-H activation at specific positions, and it is also one of the hot spots in the research field of organic chemistry. As an efficient directing group, carboxylic acid has the advantages of low cost, low toxicity, easy modification and using as traceless directing groups. Recent development on C-H functionalization directed by carboxyl group according to different coupling modes is summarized, and the representative reaction mechanism is briefly described. Existing problems with a brief outlook in this field are also presented.
The C-H activation assisted by directing groups is an important measure for selective C-H activation at specific positions, and it is also one of the hot spots in the research field of organic chemistry. As an efficient directing group, carboxylic acid has the advantages of low cost, low toxicity, easy modification and using as traceless directing groups. Recent development on C-H functionalization directed by carboxyl group according to different coupling modes is summarized, and the representative reaction mechanism is briefly described. Existing problems with a brief outlook in this field are also presented.
2019, 39(11): 3105-3113
doi: 10.6023/cjoc201904071
Abstract:
Cyanolide A and cocosolide, two 16-membered dimeric macrolide xylopyranosides, were isolated from Guam and Papua New Guinea, respectively. Their fascinating structures and outstanding biological activities had attracted great attentions from chemists. The synthesis of cyanolide A and cocosolide is reviewed based on the construction methods of tetrahydropyran ring, which involves oxo-Michael addition reaction, oxo-carbenium cyclization and transition-metal catalyzed cyclization reactions.
Cyanolide A and cocosolide, two 16-membered dimeric macrolide xylopyranosides, were isolated from Guam and Papua New Guinea, respectively. Their fascinating structures and outstanding biological activities had attracted great attentions from chemists. The synthesis of cyanolide A and cocosolide is reviewed based on the construction methods of tetrahydropyran ring, which involves oxo-Michael addition reaction, oxo-carbenium cyclization and transition-metal catalyzed cyclization reactions.
2019, 39(11): 3114-3131
doi: 10.6023/cjoc201903029
Abstract:
Transition-metal-catalyzed functionalization of unactivated C-H bonds is a highly attractive strategy for the synthesis of organic molecules, however, regioselective control is a central challenge in this field. The directing group assisted C-H functionalizations such as the use of directing templates and transient mediator, secondary interaction have attracted more attentions from researchers. The meta-C-H functionalizatioin assisted by directing groups are summarized in details. The existing problems and limitations of this field are also included. Finally, the development trend of this area is prospected.
Transition-metal-catalyzed functionalization of unactivated C-H bonds is a highly attractive strategy for the synthesis of organic molecules, however, regioselective control is a central challenge in this field. The directing group assisted C-H functionalizations such as the use of directing templates and transient mediator, secondary interaction have attracted more attentions from researchers. The meta-C-H functionalizatioin assisted by directing groups are summarized in details. The existing problems and limitations of this field are also included. Finally, the development trend of this area is prospected.
2019, 39(11): 3132-3144
doi: 10.6023/cjoc201903008
Abstract:
Alkaline phosphatase (ALP) is an important enzyme for various mammalian tissues. As a biomarker and diagnostic indicator, ALP provides important information for the applied research of molecular biology and the treatment of human diseases. Due to its reliability of information in human health, the research on fluorescence detection as important detection method has become intense in recent years. The fluorescent chemosensors are categorized by different luminous feature involving excitedstate intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) chemosensors, aggregation-induced luminescent molecules (AIE), diminishes the electron donating ability (D d-E) and disruption of the π conjugated systems (D π-C), inner filter effect (IFE) chemosensors, and other sensing systems. In the end, the development tendency of the sensing ensembles for ALP is prospected.
Alkaline phosphatase (ALP) is an important enzyme for various mammalian tissues. As a biomarker and diagnostic indicator, ALP provides important information for the applied research of molecular biology and the treatment of human diseases. Due to its reliability of information in human health, the research on fluorescence detection as important detection method has become intense in recent years. The fluorescent chemosensors are categorized by different luminous feature involving excitedstate intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) chemosensors, aggregation-induced luminescent molecules (AIE), diminishes the electron donating ability (D d-E) and disruption of the π conjugated systems (D π-C), inner filter effect (IFE) chemosensors, and other sensing systems. In the end, the development tendency of the sensing ensembles for ALP is prospected.
2019, 39(11): 3145-3153
doi: 10.6023/cjoc201904024
Abstract:
Organosilanes have been widely applied in synthetic chemistry, pharmaceuticals, agrochemicals, and materials due to the special properties. Several synthetic strategies including nucleophilic substitution, hydrosilylation of alkene, and C-H silylation have been developed. In recent years, significant progress has advanced in the cross-coupling of C-Si bond for the synthesis of organosilanes, especially in the break-through of the cross-coupling of C(sp3)-Si bond. It has become one of the hottest issues in synthetic chemistry. The recent progress on the cross-coupling of C-Si bond by using silyl reagents is summarized. The application of silyl reagents in cross-coupling for C-Si bond formation including silyl boranes, organosilyl magnesium, organosilyl zinc, unasymetric disilanes, organosilyl aluminum and organosilyl lithium reagents is mainly discussed.
Organosilanes have been widely applied in synthetic chemistry, pharmaceuticals, agrochemicals, and materials due to the special properties. Several synthetic strategies including nucleophilic substitution, hydrosilylation of alkene, and C-H silylation have been developed. In recent years, significant progress has advanced in the cross-coupling of C-Si bond for the synthesis of organosilanes, especially in the break-through of the cross-coupling of C(sp3)-Si bond. It has become one of the hottest issues in synthetic chemistry. The recent progress on the cross-coupling of C-Si bond by using silyl reagents is summarized. The application of silyl reagents in cross-coupling for C-Si bond formation including silyl boranes, organosilyl magnesium, organosilyl zinc, unasymetric disilanes, organosilyl aluminum and organosilyl lithium reagents is mainly discussed.
2019, 39(11): 3154-3161
doi: 10.6023/cjoc201904062
Abstract:
A palladium-catalyzed ortho-C(sp2)-H bond iodination of 4-arylthiazoles has been developed. Through screening of directing groups and optimazation of reaction parameters, the most efficient reaction conditions for mono-ortho-position iodination were obtained, which were applied to synthesize a series of 4-(2-iodoaryl)thiazoles with broad scope of 4-aryl-thiazole substrates. Furthermore, the iodine group can be easily transformed into other organic functional groups, which improved the application value of this methodology. At last, plausible mechanism was proposed based on an intermolecular deuterium labeling kinetic experiment and radical inhibition experiments.
A palladium-catalyzed ortho-C(sp2)-H bond iodination of 4-arylthiazoles has been developed. Through screening of directing groups and optimazation of reaction parameters, the most efficient reaction conditions for mono-ortho-position iodination were obtained, which were applied to synthesize a series of 4-(2-iodoaryl)thiazoles with broad scope of 4-aryl-thiazole substrates. Furthermore, the iodine group can be easily transformed into other organic functional groups, which improved the application value of this methodology. At last, plausible mechanism was proposed based on an intermolecular deuterium labeling kinetic experiment and radical inhibition experiments.
2019, 39(11): 3169-3175
doi: 10.6023/cjoc201904028
Abstract:
A 4-dimethylaminopyridine (DMAP)-promoted high stereoselectivity method for the synthesis of polysubstituted spiropropane pyrazolone was developed. A series of target compounds were synthesized from using pyrazolone, aromatic aldehyde and bromoacetate as raw materials, and DMAP as a base with high yield via three-component one-pot reaction. This reaction has the advantages of simple operation, high yield and good diastereotopic selectivity. In addition, this synthetic method is of great value for the study of spiropropane.
A 4-dimethylaminopyridine (DMAP)-promoted high stereoselectivity method for the synthesis of polysubstituted spiropropane pyrazolone was developed. A series of target compounds were synthesized from using pyrazolone, aromatic aldehyde and bromoacetate as raw materials, and DMAP as a base with high yield via three-component one-pot reaction. This reaction has the advantages of simple operation, high yield and good diastereotopic selectivity. In addition, this synthetic method is of great value for the study of spiropropane.
2019, 39(11): 3176-3182
doi: 10.6023/cjoc201905017
Abstract:
A facile and efficient protocol for palladium-catalyzed ortho-acylation of azoxybenzenes has been developed under aqueous conditions. In this process, the alcohols were oxidized into the corresponding aldehydes in situ, which coupled with azoxybenzenes with excellent regioselectivity, affording the acylated azoxybenzenes in moderate to good yields. A variety of functional groups were tolerated in this procedure.
A facile and efficient protocol for palladium-catalyzed ortho-acylation of azoxybenzenes has been developed under aqueous conditions. In this process, the alcohols were oxidized into the corresponding aldehydes in situ, which coupled with azoxybenzenes with excellent regioselectivity, affording the acylated azoxybenzenes in moderate to good yields. A variety of functional groups were tolerated in this procedure.
2019, 39(11): 3190-3198
doi: 10.6023/cjoc201904070
Abstract:
A facile and efficient method for the synthesis of sulfonated or sulfenylated pyrazolones catalyzed by KIO3 was established. A variety of desired products were obtained in moderate to high yields. This methodology could be conducted under mild reaction conditions without requiring any metal. Control experiments showed that the mechanism of this reaction was different from previous KIO3-catalyzed reactions. Some of these desired products showed high inhibitory activity against V. mali and B. cinerea.
A facile and efficient method for the synthesis of sulfonated or sulfenylated pyrazolones catalyzed by KIO3 was established. A variety of desired products were obtained in moderate to high yields. This methodology could be conducted under mild reaction conditions without requiring any metal. Control experiments showed that the mechanism of this reaction was different from previous KIO3-catalyzed reactions. Some of these desired products showed high inhibitory activity against V. mali and B. cinerea.
2019, 39(11): 3237-3243
doi: 10.6023/cjoc201904074
Abstract:
An efficient route to synthesize 2'-spiro[2-oxocyclopentyl]cyclopropyl nucleoside analogues via KOtBu promoted Michael addition-initiated cyclopropanation reactions of α-thymine acrylates with α-chloro-cycloalkanones has been developed. A wide range of C(2')-spirocyclic modified nucleoside analogues were obtained with excellent diastereoselectivities (>20:1) and good yields (up to 85%).
An efficient route to synthesize 2'-spiro[2-oxocyclopentyl]cyclopropyl nucleoside analogues via KOtBu promoted Michael addition-initiated cyclopropanation reactions of α-thymine acrylates with α-chloro-cycloalkanones has been developed. A wide range of C(2')-spirocyclic modified nucleoside analogues were obtained with excellent diastereoselectivities (>20:1) and good yields (up to 85%).
2019, 39(11): 3244-3249
doi: 10.6023/cjoc201903024
Abstract:
A copper-catalyzed decarbonylation cyclization to form isatins using oxygen as terminal oxidant is developed. This complementary way offers a new protocol for the synthesis of isatins through C(sp3)—H bond functionalization in Cu/O2/Co system. This system shows good reactivity and compatibility. Both electron-rich and electron-deficient functional groups can be tolerated. A postulated mechanism is proposed based on mechanistic studies and previous reports.
A copper-catalyzed decarbonylation cyclization to form isatins using oxygen as terminal oxidant is developed. This complementary way offers a new protocol for the synthesis of isatins through C(sp3)—H bond functionalization in Cu/O2/Co system. This system shows good reactivity and compatibility. Both electron-rich and electron-deficient functional groups can be tolerated. A postulated mechanism is proposed based on mechanistic studies and previous reports.
2019, 39(11): 3162-3168
doi: 10.6023/cjoc201905031
Abstract:
A new method for the synthesis of 4, 5-dihydropyrrole derivatives from γ-nitro-nitriles is described. In this procedure, the nitro groups of nitro-nitriles were reduced into aminoes under Fe+HCl systerm in methanol at 30℃ firstly. And then the amino-groups reacted with cyano groups to form target compounds via intramolecular nucleophilic addition reaction and rearrangement reaction. Under the optimized conditions, all γ-nitro-nitriles can be easily converted into 4, 5-dihydropyrrole derivatives in satisfactory yield. It shows that the reaction has better universality. Based on the experimental results, the possible reaction mechanism was proposed.
A new method for the synthesis of 4, 5-dihydropyrrole derivatives from γ-nitro-nitriles is described. In this procedure, the nitro groups of nitro-nitriles were reduced into aminoes under Fe+HCl systerm in methanol at 30℃ firstly. And then the amino-groups reacted with cyano groups to form target compounds via intramolecular nucleophilic addition reaction and rearrangement reaction. Under the optimized conditions, all γ-nitro-nitriles can be easily converted into 4, 5-dihydropyrrole derivatives in satisfactory yield. It shows that the reaction has better universality. Based on the experimental results, the possible reaction mechanism was proposed.
2019, 39(11): 3183-3189
doi: 10.6023/cjoc201904002
Abstract:
4-Dodecylbenzenesulfonic acid (DBSA) catalyzed hydrolysis reaction of β-ethylthio-β-indolyl-α, β-unsaturated ketones (1) in water to yield 3-ethanoyl/aroylacetylindoles (2) was studied. It showed that the hydrolysis of 1 in water smoothly occurred in the presence of 10 mol% DBSA in reflux water, and 2 was obtained in excellent yield.
4-Dodecylbenzenesulfonic acid (DBSA) catalyzed hydrolysis reaction of β-ethylthio-β-indolyl-α, β-unsaturated ketones (1) in water to yield 3-ethanoyl/aroylacetylindoles (2) was studied. It showed that the hydrolysis of 1 in water smoothly occurred in the presence of 10 mol% DBSA in reflux water, and 2 was obtained in excellent yield.
2019, 39(11): 3199-3206
doi: 10.6023/cjoc201904029
Abstract:
A novel and efficient approach has been developed to synthesize 2-aroylamino naphtho[1, 2-d]thiazole compounds through the reaction between 3-[1-(4-substituted naphthyl)]-1-aroylthiourea and iodosobenzene diacetate (IBD) under ambient air. A library of naphtho[1, 2-d]thiazole derivatives having a variety of substituents has been synthesized. A plausible reaction pathway has been predicted. This reaction offers a metal-free synthesis, broad substrate scope, easily accessible reactants, excellent regioselectivity, room temperature reaction conditions under ambient air. The reported method is the efficient approach for the synthesis of naphtho[1, 2-d]thiazole derivatives.
A novel and efficient approach has been developed to synthesize 2-aroylamino naphtho[1, 2-d]thiazole compounds through the reaction between 3-[1-(4-substituted naphthyl)]-1-aroylthiourea and iodosobenzene diacetate (IBD) under ambient air. A library of naphtho[1, 2-d]thiazole derivatives having a variety of substituents has been synthesized. A plausible reaction pathway has been predicted. This reaction offers a metal-free synthesis, broad substrate scope, easily accessible reactants, excellent regioselectivity, room temperature reaction conditions under ambient air. The reported method is the efficient approach for the synthesis of naphtho[1, 2-d]thiazole derivatives.
2019, 39(11): 3207-3214
doi: 10.6023/cjoc201904069
Abstract:
A simple and highly efficient palladium nanoparticles catalytic system was applied in Suzuki coupling reaction. This system could catalyze a variety of aryl halide and arylboronic acid substrates with a wide range of functional groups. A high turnover number of 90000 was obtained with the catalyst loading as low as 0.001 mol%. This catalyst system exhibited good stability and longevity.
A simple and highly efficient palladium nanoparticles catalytic system was applied in Suzuki coupling reaction. This system could catalyze a variety of aryl halide and arylboronic acid substrates with a wide range of functional groups. A high turnover number of 90000 was obtained with the catalyst loading as low as 0.001 mol%. This catalyst system exhibited good stability and longevity.
2019, 39(11): 3230-3236
doi: 10.6023/cjoc201905013
Abstract:
Human deoxyribonucleic acid (DNA) topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. To further discover Topo Ⅱα inhibitors with high efficiency and low toxicity, twenty-one 3-aryl-7-hydroxyquinolines were designed and synthesized by scaffold hopping of the lead compound 4-(6-hydroxynaph-thalen-2-yl)benzene-1, 2-diol (CS1). These compounds were evaluated for their inhibitory activity against Topo Ⅱα activity in DNA relaxation assays, and evaluated for the antitumor activity in in vitro growth inhibition assays against human triple negative breast cancer MDA-MB-231 cells and human cervical cancer HeLa cells. DNA relaxation assays showed that most compounds have inhibitory activity against Topo Ⅱα. In vitro growth inhibition assays showed that 3-(2, 4-dimethoxyphenyl)-7-hydroxyquinoline (4j) has obvious cytotoxicity against HeLa cells (IC50=0.8 μmol·L-1), and 3-(4-hydroxyphenyl)-7-hydroxyquinoline (4e) has evident cytotoxicity against both MDA-MB-231 (IC50=1.1 μmol·L-1) and HeLa cell lines (IC50=4.2 μmol·L-1). These results provide insight into the development of novel quinoline topoisomerase Ⅱα inhibitors.
Human deoxyribonucleic acid (DNA) topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. To further discover Topo Ⅱα inhibitors with high efficiency and low toxicity, twenty-one 3-aryl-7-hydroxyquinolines were designed and synthesized by scaffold hopping of the lead compound 4-(6-hydroxynaph-thalen-2-yl)benzene-1, 2-diol (CS1). These compounds were evaluated for their inhibitory activity against Topo Ⅱα activity in DNA relaxation assays, and evaluated for the antitumor activity in in vitro growth inhibition assays against human triple negative breast cancer MDA-MB-231 cells and human cervical cancer HeLa cells. DNA relaxation assays showed that most compounds have inhibitory activity against Topo Ⅱα. In vitro growth inhibition assays showed that 3-(2, 4-dimethoxyphenyl)-7-hydroxyquinoline (4j) has obvious cytotoxicity against HeLa cells (IC50=0.8 μmol·L-1), and 3-(4-hydroxyphenyl)-7-hydroxyquinoline (4e) has evident cytotoxicity against both MDA-MB-231 (IC50=1.1 μmol·L-1) and HeLa cell lines (IC50=4.2 μmol·L-1). These results provide insight into the development of novel quinoline topoisomerase Ⅱα inhibitors.
2019, 39(11): 3250-3257
doi: 10.6023/cjoc201904078
Abstract:
Selective detection of Fe3+ has considerable importance due to its active involvement in various biological processes. Based on the mechanism of excited-state intramolecular proton transfer (ESIPT) plus aggregation induced emission (AIE), a fluorescence probe of phenanthro[9, 10-d]imidazole modified by the phenolic hydroxyl (PIP-o-OH) had been designed, synthesized and applied in the detection of Fe3+. The structure of PIP-o-OH was characterized by 1H NMR, 13C NMR, IR, HRMS and X-ray single diffraction. Furthermore, a clear intramolecular hydrogen bond was observed between hydroxyl O-H and imidazole N atom in X-ray single structure, which improved the impossibility of ESIPT activity. ESIPT and AIE activities of PIP-o-OH were adequately determined by absorption, emission spectra and scanning electron microscope (SEM). The aggregated PIP-o-OH in MeOH/H2O (V:V=1:9, Hepes 10 μmol/L, pH=7.4) exhibited a good sensitivity towards Fe3+ with "turn-off" fluorescence response just after 20 s. The limit of detection (LOD) was calculated as low as 0.49 μmol/L. So it could be utilized to detect Fe3+ in biology and environmental samples. In addition, the calculation of the density functional theory (DFT) confirmed the formation of PIP-o-OH-Fe3+ complex. Also, PIP-o-OH was successfully applied to monitor Fe3+ in HeLa cells by the fluorescence change and quantificationally detect Fe3+ in water samples.
Selective detection of Fe3+ has considerable importance due to its active involvement in various biological processes. Based on the mechanism of excited-state intramolecular proton transfer (ESIPT) plus aggregation induced emission (AIE), a fluorescence probe of phenanthro[9, 10-d]imidazole modified by the phenolic hydroxyl (PIP-o-OH) had been designed, synthesized and applied in the detection of Fe3+. The structure of PIP-o-OH was characterized by 1H NMR, 13C NMR, IR, HRMS and X-ray single diffraction. Furthermore, a clear intramolecular hydrogen bond was observed between hydroxyl O-H and imidazole N atom in X-ray single structure, which improved the impossibility of ESIPT activity. ESIPT and AIE activities of PIP-o-OH were adequately determined by absorption, emission spectra and scanning electron microscope (SEM). The aggregated PIP-o-OH in MeOH/H2O (V:V=1:9, Hepes 10 μmol/L, pH=7.4) exhibited a good sensitivity towards Fe3+ with "turn-off" fluorescence response just after 20 s. The limit of detection (LOD) was calculated as low as 0.49 μmol/L. So it could be utilized to detect Fe3+ in biology and environmental samples. In addition, the calculation of the density functional theory (DFT) confirmed the formation of PIP-o-OH-Fe3+ complex. Also, PIP-o-OH was successfully applied to monitor Fe3+ in HeLa cells by the fluorescence change and quantificationally detect Fe3+ in water samples.
2019, 39(11): 3215-3222
doi: 10.6023/cjoc201904032
Abstract:
Tandem Pd(OAc)2/CuI catalyzed coupling/cyclization/chalcogenylation reaction of gem-dibromovinylanilines with boronic acids and dichalcogenides has been developed, which provides a new synthetic approach to 3-sulfenyl-and 3-selenylindoles. Various functional groups such as methoxyl, halides and trifluoromethyl groups in the substrates are tolerated.
Tandem Pd(OAc)2/CuI catalyzed coupling/cyclization/chalcogenylation reaction of gem-dibromovinylanilines with boronic acids and dichalcogenides has been developed, which provides a new synthetic approach to 3-sulfenyl-and 3-selenylindoles. Various functional groups such as methoxyl, halides and trifluoromethyl groups in the substrates are tolerated.
2019, 39(11): 3223-3229
doi: 10.6023/cjoc201904051
Abstract:
The cleavage of C-C bonds is a key method for synthesis of useful intermediates. A novel amine-promoted C-C bond cleavage of α-halo ketones was reported. Oxidant-free and metal-free conditions are the striking features of the protocol. In this simple method, a variety of α-acetoxyaryl ketone compounds were prepared from commercially available α-halo ketones in good to excellent yields.
The cleavage of C-C bonds is a key method for synthesis of useful intermediates. A novel amine-promoted C-C bond cleavage of α-halo ketones was reported. Oxidant-free and metal-free conditions are the striking features of the protocol. In this simple method, a variety of α-acetoxyaryl ketone compounds were prepared from commercially available α-halo ketones in good to excellent yields.
2019, 39(11): 3258-3263
doi: 10.6023/cjoc201902031
Abstract:
The utilization of sustainable resources such as biomass to produce fuels and chemicals has recently attracted significant attention due to the depletion of fossil reserves, increasing energy demand, and growing environmental concerns. Long-chain fatty acids, which are major constituents of plant oil, are important feedstock for biorefinery. Besides producing well-known biodiesels, the hydrogenation of fatty acids to fatty alcohols has recently drawn significant attention due to the versatility and growing market value of fatty alcohols. An example of heterogenous iron-catalyzed selective hydrogenation of stearic acid to stearyl alcohol is reported. Comparing with other reported non-noble metal centers, such as Co and Ni, Fe is 3000~30000 times more abundant and 20~150 times cheaper, thus making our method more economic and attractive. The iron catalyst was prepared by simultaneous pyrolysis of iron precursor[Fe(acac)3] and nitrogen-doped carbon precursor (melamine) onto alumina, bearing Fe3C active phase and nitrogen-doped carbon-alumina hybrid support. The optimization of preparation parameter showed that the optimal pyrolysis temperature is 900℃, while the best mass fraction of iron is 20%. The replacement of Fe(acac)3 with Fe(NO3)3 led to inferior catalytic performance, which was due to undesired redox reaction between NO3- and melamine during pyrolysis that hampered the reaction between Fe and melamine to form Fe3C active phase. Instead, hercynite phase became the predominant phase. The exploration of reaction parameter showed that the optimal reaction temperature is 320℃, and the best H2 pressure is 4 MPa. The time course for stearic acid conversion shows that stearic acid was rapidly converted into stearyl alcohol with yield of 88.6% within 0.5 h, and then gradually converted into octadecane with yield of 90% at 4 h. The unsatisfactory stability of the iron catalyst is probably due to the decomposition of Fe3C active phase to metallic Fe phase during recycling tests.
The utilization of sustainable resources such as biomass to produce fuels and chemicals has recently attracted significant attention due to the depletion of fossil reserves, increasing energy demand, and growing environmental concerns. Long-chain fatty acids, which are major constituents of plant oil, are important feedstock for biorefinery. Besides producing well-known biodiesels, the hydrogenation of fatty acids to fatty alcohols has recently drawn significant attention due to the versatility and growing market value of fatty alcohols. An example of heterogenous iron-catalyzed selective hydrogenation of stearic acid to stearyl alcohol is reported. Comparing with other reported non-noble metal centers, such as Co and Ni, Fe is 3000~30000 times more abundant and 20~150 times cheaper, thus making our method more economic and attractive. The iron catalyst was prepared by simultaneous pyrolysis of iron precursor[Fe(acac)3] and nitrogen-doped carbon precursor (melamine) onto alumina, bearing Fe3C active phase and nitrogen-doped carbon-alumina hybrid support. The optimization of preparation parameter showed that the optimal pyrolysis temperature is 900℃, while the best mass fraction of iron is 20%. The replacement of Fe(acac)3 with Fe(NO3)3 led to inferior catalytic performance, which was due to undesired redox reaction between NO3- and melamine during pyrolysis that hampered the reaction between Fe and melamine to form Fe3C active phase. Instead, hercynite phase became the predominant phase. The exploration of reaction parameter showed that the optimal reaction temperature is 320℃, and the best H2 pressure is 4 MPa. The time course for stearic acid conversion shows that stearic acid was rapidly converted into stearyl alcohol with yield of 88.6% within 0.5 h, and then gradually converted into octadecane with yield of 90% at 4 h. The unsatisfactory stability of the iron catalyst is probably due to the decomposition of Fe3C active phase to metallic Fe phase during recycling tests.
2019, 39(11): 3264-3268
doi: 10.6023/cjoc201905010
Abstract:
Three new meroterpenoids of ganoduriporols C~E were isolated from the fruiting bodies of Ganoderma ahmadii Steyaret by silica gel column, high performance liquid chromatography (HPLC) and other chromatography methods. Their structures were determined by spectroscopic techniques including NMR and HR-ESI-MS. Their inhibitory activities for protein tyrosine phosphatase 1B (PTP1B) in vitro were tested. The results showed that the three compounds had obvious PTP1B inhibitory activitiy with the IC50 values of 19.1, 17.81, and 29.6 μmol·L-1, respectively.
Three new meroterpenoids of ganoduriporols C~E were isolated from the fruiting bodies of Ganoderma ahmadii Steyaret by silica gel column, high performance liquid chromatography (HPLC) and other chromatography methods. Their structures were determined by spectroscopic techniques including NMR and HR-ESI-MS. Their inhibitory activities for protein tyrosine phosphatase 1B (PTP1B) in vitro were tested. The results showed that the three compounds had obvious PTP1B inhibitory activitiy with the IC50 values of 19.1, 17.81, and 29.6 μmol·L-1, respectively.
2019, 39(11): 3269-3276
doi: 10.6023/cjoc201904003
Abstract:
Three optically pure dehydroabietylamine derivatives, acetyldehydroabietylamine-6, 7-(3-mercapto)-1, 2, 4-triazine (5), acetyldehydroabietylamine-6, 7-indole (7) and 12-(2-aminothiazole)-acetyldehydroabietylamine (10), were obtained by introducing different aromatic heterocycles into the B and C rings of optically pure dehydroabietylamine, which is derived from natural product of rosin, according to superposition principle of activity groups. The results of fluorescence spectroscopy and circular dichroism studies indicate that 5, 7 and 10 could interact with DNA, and the binding ability followed the order 5 > 10 > 7. Gel electrophoresis experiments suggest that 5, 7 and 10 could scissor pBR 322 plasmid DNA into single strands and 5 was the strongest cutter. In addition, the inhibitory rates of dehydroabietylamine and its derivatives 5, 7 and 10 combined with copper chloride (32 μmol·L-1) on the proliferation of human breast cancer cells MCF-7 were 86.0% (1), 86.7% (5), 34.4% (7) and 0 (10), respectively.
Three optically pure dehydroabietylamine derivatives, acetyldehydroabietylamine-6, 7-(3-mercapto)-1, 2, 4-triazine (5), acetyldehydroabietylamine-6, 7-indole (7) and 12-(2-aminothiazole)-acetyldehydroabietylamine (10), were obtained by introducing different aromatic heterocycles into the B and C rings of optically pure dehydroabietylamine, which is derived from natural product of rosin, according to superposition principle of activity groups. The results of fluorescence spectroscopy and circular dichroism studies indicate that 5, 7 and 10 could interact with DNA, and the binding ability followed the order 5 > 10 > 7. Gel electrophoresis experiments suggest that 5, 7 and 10 could scissor pBR 322 plasmid DNA into single strands and 5 was the strongest cutter. In addition, the inhibitory rates of dehydroabietylamine and its derivatives 5, 7 and 10 combined with copper chloride (32 μmol·L-1) on the proliferation of human breast cancer cells MCF-7 were 86.0% (1), 86.7% (5), 34.4% (7) and 0 (10), respectively.
2019, 39(11): 3277-3282
doi: 10.6023/cjoc201905038
Abstract:
A dual-reactable H2S fluorescent probe was designed and synthesized by employing ortho-fluoro-substituted coumarin azide and 7-nitrobenzofurazan-piperazine as the H2S reactive groups and the fluorescence quenching groups. The recognition behaviors of the probe to H2S were investigated and the results showed that the probe exhibited high selectivity and sensitivity. The fluorescence off-on enhancement was ca. 3600-fold, and the detection limit was 4.0×10-8 mol/L. The results of enzyme activity test indicated that the probe could be used for cystathionine β-synthase (CBS) activity detection and inhibitor screening. Furthermore, the probe was successfully applied for the imaging of H2S in living cells.
A dual-reactable H2S fluorescent probe was designed and synthesized by employing ortho-fluoro-substituted coumarin azide and 7-nitrobenzofurazan-piperazine as the H2S reactive groups and the fluorescence quenching groups. The recognition behaviors of the probe to H2S were investigated and the results showed that the probe exhibited high selectivity and sensitivity. The fluorescence off-on enhancement was ca. 3600-fold, and the detection limit was 4.0×10-8 mol/L. The results of enzyme activity test indicated that the probe could be used for cystathionine β-synthase (CBS) activity detection and inhibitor screening. Furthermore, the probe was successfully applied for the imaging of H2S in living cells.
2019, 39(11): 3283-3288
doi: 10.6023/cjoc201905035
Abstract:
By splicing the triazene structure with 1, 3, 4-thiadiazole and amide, fourteen unreported 1, 3, 4-thiadiazole triazene amide derivatives were synthesized. The structures of these compounds were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). By using the typical triazene drug dacarbazine as a reference, the activity detections of human esophageal cancer cells (EC109), human gastric cancer cells (MGC803) and human prostate cancer cells (PC-3) were carried out. The results showed that compounds 8a, 8h, 8i, 8k, and 8l had the best inhibitory activity against human prostate cancer cells (PC-3). And their IC50 values were 33.02, 34.05, 7.71, 4.82, 23.84 μmol·L-1, which were far lower than the control drug their IC50 values were 33.02, 34.05, 7.71, 4.82, 23.84 μmol·L-1, which were far lower than the control drug dacarbazine (146.43 μmol·L-1).
By splicing the triazene structure with 1, 3, 4-thiadiazole and amide, fourteen unreported 1, 3, 4-thiadiazole triazene amide derivatives were synthesized. The structures of these compounds were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). By using the typical triazene drug dacarbazine as a reference, the activity detections of human esophageal cancer cells (EC109), human gastric cancer cells (MGC803) and human prostate cancer cells (PC-3) were carried out. The results showed that compounds 8a, 8h, 8i, 8k, and 8l had the best inhibitory activity against human prostate cancer cells (PC-3). And their IC50 values were 33.02, 34.05, 7.71, 4.82, 23.84 μmol·L-1, which were far lower than the control drug their IC50 values were 33.02, 34.05, 7.71, 4.82, 23.84 μmol·L-1, which were far lower than the control drug dacarbazine (146.43 μmol·L-1).
2019, 39(11): 3289-3293
doi: 10.6023/cjoc201903035
Abstract:
By silica gel, MCI column chromatographic and preparative high performance liquid chromatography (HPLC) technologies, three new bibenzyl derivatives were isolated from the tubes of Dendrobium nobile. One racemic compound was further purified by chiral (HPLC) to obtain a pair of enantiomers 1a and 1b, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. By using spectroscopic techniques including NMR and HR-ESIMS, the structures of compounds 1~3 were identified as didendronbiline A (1), dendronbiline B (2), and dendronbiline C(3).
By silica gel, MCI column chromatographic and preparative high performance liquid chromatography (HPLC) technologies, three new bibenzyl derivatives were isolated from the tubes of Dendrobium nobile. One racemic compound was further purified by chiral (HPLC) to obtain a pair of enantiomers 1a and 1b, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. By using spectroscopic techniques including NMR and HR-ESIMS, the structures of compounds 1~3 were identified as didendronbiline A (1), dendronbiline B (2), and dendronbiline C(3).
2019, 39(11): 3299-3303
doi: 10.6023/cjoc201903032
Abstract:
Benzoimidazole and chromen derivatives exhibit a variety of important biological activities. Chromens incorporating benzoimidazole moiety have high Rho kinase inhibitory activity. However, the effective synthetic method for the preparation of these compounds is rare. The efficient synthesis of new substituted 3-(1H-benzo[d]imidazol-2-yl)-4H-chromens in 48%~89% yields via one-pot, three-component reaction of 2-(1H-benzo[d]imidazol-2-yl)acetonitrile with aromatic aldehydes and 5, 5-dimethylcyclohexane-1, 3-dione was studied. This reaction was carried out in EtOH in the presence of pyridine under reflux conditions. All reactions were completed within 1 to 3 h.
Benzoimidazole and chromen derivatives exhibit a variety of important biological activities. Chromens incorporating benzoimidazole moiety have high Rho kinase inhibitory activity. However, the effective synthetic method for the preparation of these compounds is rare. The efficient synthesis of new substituted 3-(1H-benzo[d]imidazol-2-yl)-4H-chromens in 48%~89% yields via one-pot, three-component reaction of 2-(1H-benzo[d]imidazol-2-yl)acetonitrile with aromatic aldehydes and 5, 5-dimethylcyclohexane-1, 3-dione was studied. This reaction was carried out in EtOH in the presence of pyridine under reflux conditions. All reactions were completed within 1 to 3 h.
2019, 39(11): 3294-3298
doi: 10.6023/cjoc201903007
Abstract:
An one-pot iron-catalyzed oxidative formylation of 2-methylquinolines to produce 2-quinoline carboxaldehydes under microwave irradiation has been achieved by employing O2 as the oxygen donor. The reaction was general for the substrates with a wide range of functional groups, providing a yield of 48%~80%. The preliminary mechanistic studies revealed that the reaction underwent a radical pathway. Advantages of this method include the easy operation, short reaction time and good selectivity.
An one-pot iron-catalyzed oxidative formylation of 2-methylquinolines to produce 2-quinoline carboxaldehydes under microwave irradiation has been achieved by employing O2 as the oxygen donor. The reaction was general for the substrates with a wide range of functional groups, providing a yield of 48%~80%. The preliminary mechanistic studies revealed that the reaction underwent a radical pathway. Advantages of this method include the easy operation, short reaction time and good selectivity.
2019, 39(11): 3304-3305
doi: 10.6023/cjoc201900001
Abstract:
2019, 39(11): 3306-3307
doi: 10.6023/cjoc201900003
Abstract:
2019, 39(11): 3308-3309
doi: 10.6023/cjoc201900004
Abstract:
2019, 39(11): 3310-3311
doi: 10.6023/cjoc201900005
Abstract:
2019, 39(11): 3312-3313
doi: 10.6023/cjoc201900006
Abstract:
