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2017 Volume 37 Issue 3
2017, 37(3): 543-554
doi: 10.6023/cjoc20161101
Abstract:
The[4+4] photodimerizations of anthracene and its derivatives have been extensively studied for over a century. This classic photochemical reaction features broad substrate scope, user-friendly operation, and controllable reversibility. However, the synthetic applications of anthracene photodimerizations have been underdeveloped thus far, largely because of stereoisomer separation and solubility problems of the dianthracene products. Considering that the dianthracene products display unique molecular rigidity and geometry, further studies to improve the synthetic utility of anthracene photodimerizations should be warranted. This review summarizes the representative works of anthracene photodimerizations since the beginning of the 21st century, highlighting the synthetic advances to improve the reaction regio-and enantio-selectivity, as well as the synthetic applications toward functional organic molecules and molecular machines.
The[4+4] photodimerizations of anthracene and its derivatives have been extensively studied for over a century. This classic photochemical reaction features broad substrate scope, user-friendly operation, and controllable reversibility. However, the synthetic applications of anthracene photodimerizations have been underdeveloped thus far, largely because of stereoisomer separation and solubility problems of the dianthracene products. Considering that the dianthracene products display unique molecular rigidity and geometry, further studies to improve the synthetic utility of anthracene photodimerizations should be warranted. This review summarizes the representative works of anthracene photodimerizations since the beginning of the 21st century, highlighting the synthetic advances to improve the reaction regio-and enantio-selectivity, as well as the synthetic applications toward functional organic molecules and molecular machines.
2017, 37(3): 555-565
doi: 10.6023/cjoc201609006
Abstract:
N-Fused heterocycles are an important class of organic compounds. As a basic scaffold of a wide variety of biologically active alkaloids and synthetic pharmaceuticals and agrochemicals, the construction methods of N-fused heterocycles have attracted much attention. Significant efforts have been devoted to the application of the nanocrystalline metal oxides as heterogeneous, efficient and environmentally friendly catalyst in organic reaction. This review provides a summary of the synthesis of the different kinds of N-fused heterocycles in recent 5 years catalyzed by the nanocrystalline metal oxides.
N-Fused heterocycles are an important class of organic compounds. As a basic scaffold of a wide variety of biologically active alkaloids and synthetic pharmaceuticals and agrochemicals, the construction methods of N-fused heterocycles have attracted much attention. Significant efforts have been devoted to the application of the nanocrystalline metal oxides as heterogeneous, efficient and environmentally friendly catalyst in organic reaction. This review provides a summary of the synthesis of the different kinds of N-fused heterocycles in recent 5 years catalyzed by the nanocrystalline metal oxides.
2017, 37(3): 566-576
doi: 10.6023/cjoc201610011
Abstract:
Nitrogen-containing compounds are extremely important because of their abundance in synthetic organic compounds, natural products and pharmaceutical agents. Recently, transition metal-free C-N bond-formation via radical procedures has attracted wide interest. The recent advances in C-N bond formation via C (sp3, sp2 or sp)-H bond activation under transition metal-free conditions are summarized.
Nitrogen-containing compounds are extremely important because of their abundance in synthetic organic compounds, natural products and pharmaceutical agents. Recently, transition metal-free C-N bond-formation via radical procedures has attracted wide interest. The recent advances in C-N bond formation via C (sp3, sp2 or sp)-H bond activation under transition metal-free conditions are summarized.
2017, 37(3): 577-585
doi: 10.6023/cjoc201609015
Abstract:
Graphite carbon nitride (g-C3N4) is a new metal-free photocatalyst. Due to its 2.7 eV band gap which makes it being absorbed in the visible region, as well as unique structure which gives it good photocatalytic activity, g-C3N4 has attracted more and more attentions in visible photocatalysis field. The application of photocatalysis with g-C3N4 in organic reactions, such as oxidation reaction, reduction reaction, carbon-carbon bond formation, cyclization reaction and other organic reactions, is summarized and its future outlook is also discussed.
Graphite carbon nitride (g-C3N4) is a new metal-free photocatalyst. Due to its 2.7 eV band gap which makes it being absorbed in the visible region, as well as unique structure which gives it good photocatalytic activity, g-C3N4 has attracted more and more attentions in visible photocatalysis field. The application of photocatalysis with g-C3N4 in organic reactions, such as oxidation reaction, reduction reaction, carbon-carbon bond formation, cyclization reaction and other organic reactions, is summarized and its future outlook is also discussed.
2017, 37(3): 586-602
doi: 10.6023/cjoc201609030
Abstract:
Unstrained carbon-carbon single bonds are ubiquitous in organic compounds, the cleavage of this bond is one of the most significant and challenging subject in organic chemistry. Oxidative cleavage of unstrained carbon-carbon single bond has become a great tendency, in particular, the transition metal-catalyzed oxidative cleavage reaction, which had made significant progress in recent years. Oxygen, as the most inexpensive and environmentally friendly oxidant, has been widely used in various organic reactions. This review is an overview of recent advances of unstrained carbon-carbon single bond cleavage with oxygen according to whether transition metal catalysis is needed.
Unstrained carbon-carbon single bonds are ubiquitous in organic compounds, the cleavage of this bond is one of the most significant and challenging subject in organic chemistry. Oxidative cleavage of unstrained carbon-carbon single bond has become a great tendency, in particular, the transition metal-catalyzed oxidative cleavage reaction, which had made significant progress in recent years. Oxygen, as the most inexpensive and environmentally friendly oxidant, has been widely used in various organic reactions. This review is an overview of recent advances of unstrained carbon-carbon single bond cleavage with oxygen according to whether transition metal catalysis is needed.
2017, 37(3): 603-607
doi: 10.6023/cjoc201612033
Abstract:
In this research, the structure of the bis-naphthalene molecular resulting from 2-naphthol and 1, 1, 1', 1'-tetramethoxypropane was modified, and six derivatives with different substituents, sidewalls or bridges were synthesized. Their structures were studied by X-ray crystallography and molecular modelling, and all possess curved architectures. Electrostatic potential energy surfaces show that their inner cavities are electron-rich, and may complex with organic cations through cation-π interactions. Their binding stoichiometry and association constants with the 1, 4-diazabicyclo[2.2.2]octane (DABCO)-based organic cation were studied by 1H NMR titration and Job's plot. The results show that electron-rich molecules have much stronger association, and reducing the carbon atom in the bridge significantly decreases their association ability. These novel curved structures may work as building blocks for the construction of new macrocyclic receptors.
In this research, the structure of the bis-naphthalene molecular resulting from 2-naphthol and 1, 1, 1', 1'-tetramethoxypropane was modified, and six derivatives with different substituents, sidewalls or bridges were synthesized. Their structures were studied by X-ray crystallography and molecular modelling, and all possess curved architectures. Electrostatic potential energy surfaces show that their inner cavities are electron-rich, and may complex with organic cations through cation-π interactions. Their binding stoichiometry and association constants with the 1, 4-diazabicyclo[2.2.2]octane (DABCO)-based organic cation were studied by 1H NMR titration and Job's plot. The results show that electron-rich molecules have much stronger association, and reducing the carbon atom in the bridge significantly decreases their association ability. These novel curved structures may work as building blocks for the construction of new macrocyclic receptors.
2017, 37(3): 608-616
doi: 10.6023/cjoc201609020
Abstract:
Quantum chemical studies on the intramolecular N-arylation mechanism and reactivity of N-(2-halogen phenyl)-N'-phenyl ethyl amidines in dimethyl sulfoxide (DMSO) for the synthesis of benzimidazoles by base-catalyzed have been performed at MP2/6-311+G**//B3LYP/6-311+G** level of theory. The results indicate that the mechanism of the title reactions is not the radical mechanism or stepwise SNAr pathway, but the concerted SNAr pathway with a transition state, which is compared with the conclusion of Bolm et al. The reactivity of the title reactions can not be interpreted by the geometric looseness or natural population analysis. Multi parameter fitting reveals that the reactivity of the title reactions is controlled mostly by the regional nucleophilicity index ωN10- of the nucleophile N10 atom or highest occupied molecular orbital energy EHOMO of the reactant, the other factor is the charges of the nucleophilic atom N10, while the charges of the C2 atom and the geometric looseness L% have almost no effect on the reaction energy barrier. The relative energies and the reactivity of the title reactions attained at MP2/6-311+G**//B3LYP/6-311+G** level of theory are better agreement with the experimental results compared with the other methods.
Quantum chemical studies on the intramolecular N-arylation mechanism and reactivity of N-(2-halogen phenyl)-N'-phenyl ethyl amidines in dimethyl sulfoxide (DMSO) for the synthesis of benzimidazoles by base-catalyzed have been performed at MP2/6-311+G**//B3LYP/6-311+G** level of theory. The results indicate that the mechanism of the title reactions is not the radical mechanism or stepwise SNAr pathway, but the concerted SNAr pathway with a transition state, which is compared with the conclusion of Bolm et al. The reactivity of the title reactions can not be interpreted by the geometric looseness or natural population analysis. Multi parameter fitting reveals that the reactivity of the title reactions is controlled mostly by the regional nucleophilicity index ωN10- of the nucleophile N10 atom or highest occupied molecular orbital energy EHOMO of the reactant, the other factor is the charges of the nucleophilic atom N10, while the charges of the C2 atom and the geometric looseness L% have almost no effect on the reaction energy barrier. The relative energies and the reactivity of the title reactions attained at MP2/6-311+G**//B3LYP/6-311+G** level of theory are better agreement with the experimental results compared with the other methods.
2017, 37(3): 617-623
doi: 10.6023/cjoc201610014
Abstract:
A rhodamine-based water-soluble fluorescent probe of Fe3+(T1) was designed and synthesized, in which a carboxy was linked to enhance its water solubility. Its structure was characterized by 1H NMR, 13C NMR and HRMS-ESI. The fluorescent probe showed remarkable "turn-on" fluorescent responses to Fe3+ with good selectivity over other competitive cations. It has a good water solubility that the recognition properties of the probe with Fe3+ ions can be investigated in DMF/Tris-HCl (V:V=1:9, pH=7.4). The fluorescence imaging experiments of Fe3+ in MCF-7 living cells demonstrated that the probe had a good cell-membrane permeability and it could be used in biological systems.
A rhodamine-based water-soluble fluorescent probe of Fe3+(T1) was designed and synthesized, in which a carboxy was linked to enhance its water solubility. Its structure was characterized by 1H NMR, 13C NMR and HRMS-ESI. The fluorescent probe showed remarkable "turn-on" fluorescent responses to Fe3+ with good selectivity over other competitive cations. It has a good water solubility that the recognition properties of the probe with Fe3+ ions can be investigated in DMF/Tris-HCl (V:V=1:9, pH=7.4). The fluorescence imaging experiments of Fe3+ in MCF-7 living cells demonstrated that the probe had a good cell-membrane permeability and it could be used in biological systems.
2017, 37(3): 624-629
doi: 10.6023/cjoc201611004
Abstract:
A new macrocyclic norbornene-based bis-triazole (1) containing anthracene fluorophore and its acyclic analog 2 have been designed and synthesized by "click reaction", and their fluorescence recognition abilities towards various metal ions have been investigated. In CH3CN-H2O (V:V=90:10) solution, cyclic receptor 1 shows excusive turn-off fluorescent sensing of Zn2+. However, acyclic receptor 2 exhibits fluorescence changes towards Zn2+, Hg2+ and Cu2+. Upon addition Zn2+, the fluorescence of 2 give a large enhancement, while the addition of Hg2+ and Cu2+ leads a fluorescence quenching effect. In addition, the binding mechanisms between receptors and metal ions have been discussed via 1H NMR titration and density functional theory (DFT) calculation technique.
A new macrocyclic norbornene-based bis-triazole (1) containing anthracene fluorophore and its acyclic analog 2 have been designed and synthesized by "click reaction", and their fluorescence recognition abilities towards various metal ions have been investigated. In CH3CN-H2O (V:V=90:10) solution, cyclic receptor 1 shows excusive turn-off fluorescent sensing of Zn2+. However, acyclic receptor 2 exhibits fluorescence changes towards Zn2+, Hg2+ and Cu2+. Upon addition Zn2+, the fluorescence of 2 give a large enhancement, while the addition of Hg2+ and Cu2+ leads a fluorescence quenching effect. In addition, the binding mechanisms between receptors and metal ions have been discussed via 1H NMR titration and density functional theory (DFT) calculation technique.
Palladium-Catalyzed C-H Alkoxycarbonylation of Caffeines: Synthesis of 8-Ester-substituted Caffeines
2017, 37(3): 630-635
doi: 10.6023/cjoc201610028
Abstract:
Carbonyl-substituted caffeine derivatives have attracted much attention due to their potent pharmaceutical activity and interesting fluorescent properties. An efficient synthesis of 8-ester-substituted caffeines through palladium-catalyzed C-H alkoxycarbonylation was developed. The reaction was carried out in the presence of PdCl2(PPh3)2 and Cu (OAc)2 under 101 kPa CO atmosphere in 1, 4-dioxane, providing diversified 8-ester-substituted caffeines in reasonable to good yields. The approach was characterized by using atmospheric pressure of carbon monoxide and broad functional group tolerance.
Carbonyl-substituted caffeine derivatives have attracted much attention due to their potent pharmaceutical activity and interesting fluorescent properties. An efficient synthesis of 8-ester-substituted caffeines through palladium-catalyzed C-H alkoxycarbonylation was developed. The reaction was carried out in the presence of PdCl2(PPh3)2 and Cu (OAc)2 under 101 kPa CO atmosphere in 1, 4-dioxane, providing diversified 8-ester-substituted caffeines in reasonable to good yields. The approach was characterized by using atmospheric pressure of carbon monoxide and broad functional group tolerance.
2017, 37(3): 636-645
doi: 10.6023/cjoc201608032
Abstract:
Design and synthesis of well-defined hetero-functional cubic silsesquioxane remain as international research focuses and challenges. In this work, we demonstrated in detail the synthesis of two Janus hetero-functional cubic silsesquioxane. We applied similar "bottom-up" method to construct the aimed Janus HFCSQ, which was carried out by using cyclic tetrasiloxanes as synthetic platforms and followed by further hydrolysis and cage-closure. The obtained products exhibited good solubility in THF, CHCl3 and DMSO, which embodied themselves potential use in further derivations and processing. The precise structure of these obtained Janus HFCSQ were fully characterized by FTIR, 1H NMR, Maldi-tof MS, 29Si NMR, WAXD and TGA. Red-shifts observed from Photoluminescence UV-vis analysis further confirmed extended conjugation of the silsesquioxane cages, which in turn proved the formation of completed cages.This work provided us a versatile novel method to prepare the resulting Janus HFCSQs, which can widely expand the species of silsesquioxane monomers and applications as well.
Design and synthesis of well-defined hetero-functional cubic silsesquioxane remain as international research focuses and challenges. In this work, we demonstrated in detail the synthesis of two Janus hetero-functional cubic silsesquioxane. We applied similar "bottom-up" method to construct the aimed Janus HFCSQ, which was carried out by using cyclic tetrasiloxanes as synthetic platforms and followed by further hydrolysis and cage-closure. The obtained products exhibited good solubility in THF, CHCl3 and DMSO, which embodied themselves potential use in further derivations and processing. The precise structure of these obtained Janus HFCSQ were fully characterized by FTIR, 1H NMR, Maldi-tof MS, 29Si NMR, WAXD and TGA. Red-shifts observed from Photoluminescence UV-vis analysis further confirmed extended conjugation of the silsesquioxane cages, which in turn proved the formation of completed cages.This work provided us a versatile novel method to prepare the resulting Janus HFCSQs, which can widely expand the species of silsesquioxane monomers and applications as well.
2017, 37(3): 646-651
doi: 10.6023/cjoc201609014
Abstract:
The development of a convenient and effective[2+2] cycloaddition for the synthesis of highly substituted cyclobutanes with excellent selectivity is of great scientific significance. Using p-toluenesulfonic acid monohydrate (TsOH·H2O) as catalyst and pyridinium chlorochromate (PCC) as oxidant, the intermolecular[2+2] cycloaddition of allenylic esters generated in-situ from 2-(3-hydroxy-3, 3-diphenylprop) benzaldehydes to constructure various cyclobutane compounds is reported. This protocol has some distinct advantages of mild reaction conditions, atom economy and high regioselectivity. The structures of relevant products were characterized by 1H NMR, 13C NMR, HRMS and X-ray crystal diffraction. In addition, a possible mechanism for this transformation was depicted.
The development of a convenient and effective[2+2] cycloaddition for the synthesis of highly substituted cyclobutanes with excellent selectivity is of great scientific significance. Using p-toluenesulfonic acid monohydrate (TsOH·H2O) as catalyst and pyridinium chlorochromate (PCC) as oxidant, the intermolecular[2+2] cycloaddition of allenylic esters generated in-situ from 2-(3-hydroxy-3, 3-diphenylprop) benzaldehydes to constructure various cyclobutane compounds is reported. This protocol has some distinct advantages of mild reaction conditions, atom economy and high regioselectivity. The structures of relevant products were characterized by 1H NMR, 13C NMR, HRMS and X-ray crystal diffraction. In addition, a possible mechanism for this transformation was depicted.
2017, 37(3): 652-657
doi: 10.6023/cjoc201610009
Abstract:
A nickel-catalyzed intramolecular Grignard-type addition of aryl bromides to C=O was developed. By using Ni (dppe) Br2 as a catalyst and zinc powder as a reducing agent, the reactions of 2-((2-bromophenyl) amino)-1-arylethanones proceeded smoothly in 1, 2-dimethoxyethane solvent to afford 3-hydroxyindolines as intermediates, which underwent dehydration reaction to furnish a range of indole derivatives in moderate to excellent yields (up to 90%).
A nickel-catalyzed intramolecular Grignard-type addition of aryl bromides to C=O was developed. By using Ni (dppe) Br2 as a catalyst and zinc powder as a reducing agent, the reactions of 2-((2-bromophenyl) amino)-1-arylethanones proceeded smoothly in 1, 2-dimethoxyethane solvent to afford 3-hydroxyindolines as intermediates, which underwent dehydration reaction to furnish a range of indole derivatives in moderate to excellent yields (up to 90%).
2017, 37(3): 658-666
doi: 10.6023/cjoc201609021
Abstract:
This paper is designed to study the bioactive natural products sourced from the deep-sea sediment-derived Strep-tomyces malaysiensis OUCMDZ-2167. By means of column chromatography on silica gel, sephadex LH-20 and semi-prepa-rative HPLC, a new furan derivative 1 and ten known compounds 2~11 were isolated and purified from the fermentation broth of S. malaysiensis OUCMDZ-2167. Their structures were respectively elucidated as methyl 4-(hydroxymethyl) furan-2-carboxylate (1), dimethyl furan-2, 4-dicarboxylate (2), geldanamycin (3), 17-O-demethylgeldanamycin (4), nigericin (5), nigericin sodium salt (6), 30-O-acetylnigericin (7), abierixin (8), elaiophylin (9), surugapyrone A (10) and germicidin A (11), by analyzing the MS, UV, IR, NMR and specific rotations. The cytotoxicities against MCF-7, A549 and K562 were evaluated by thiazolyl blue tetrazolium bromide (MTT) and the cell counting kit-8 (CCK-8) methods. The results showed that compounds 3 and 5~9 exhib-ited the cytotoxicities against A549 cell with the half inhibitory concentrations (IC50) of 2.56±0.30, 0.96±0.03, 0.96±0.04, 0.81±0.05, 7.11±0.90 and 4.09±0.70 μmol·L-1, respectively. Compounds 5~9 displayed the cytotoxicities against K562 cells with the IC50 values of 1.46±0.11, 1.08±0.03, 0.48±0.10, 4.68±0.19 and 9.60±0.50 μmol·L-1, respectively. And compounds 5, 8 and 9 showed cytotoxicities against MCF-7 cell with the IC50 values of 0.29±0.15, 4.05±0.50 and 4.81±0.70 μmol·L-1, respectively. It is the first time to report the cytotoxicities of compounds 5~8 against K562 and A549 cell lines and against MCF-7 cell line.
This paper is designed to study the bioactive natural products sourced from the deep-sea sediment-derived Strep-tomyces malaysiensis OUCMDZ-2167. By means of column chromatography on silica gel, sephadex LH-20 and semi-prepa-rative HPLC, a new furan derivative 1 and ten known compounds 2~11 were isolated and purified from the fermentation broth of S. malaysiensis OUCMDZ-2167. Their structures were respectively elucidated as methyl 4-(hydroxymethyl) furan-2-carboxylate (1), dimethyl furan-2, 4-dicarboxylate (2), geldanamycin (3), 17-O-demethylgeldanamycin (4), nigericin (5), nigericin sodium salt (6), 30-O-acetylnigericin (7), abierixin (8), elaiophylin (9), surugapyrone A (10) and germicidin A (11), by analyzing the MS, UV, IR, NMR and specific rotations. The cytotoxicities against MCF-7, A549 and K562 were evaluated by thiazolyl blue tetrazolium bromide (MTT) and the cell counting kit-8 (CCK-8) methods. The results showed that compounds 3 and 5~9 exhib-ited the cytotoxicities against A549 cell with the half inhibitory concentrations (IC50) of 2.56±0.30, 0.96±0.03, 0.96±0.04, 0.81±0.05, 7.11±0.90 and 4.09±0.70 μmol·L-1, respectively. Compounds 5~9 displayed the cytotoxicities against K562 cells with the IC50 values of 1.46±0.11, 1.08±0.03, 0.48±0.10, 4.68±0.19 and 9.60±0.50 μmol·L-1, respectively. And compounds 5, 8 and 9 showed cytotoxicities against MCF-7 cell with the IC50 values of 0.29±0.15, 4.05±0.50 and 4.81±0.70 μmol·L-1, respectively. It is the first time to report the cytotoxicities of compounds 5~8 against K562 and A549 cell lines and against MCF-7 cell line.
2017, 37(3): 667-674
doi: 10.6023/cjoc201609027
Abstract:
An efficient and stereoselective synthesis of quinolinone-and pyridinone-fused 2, 8-dioxabicyclo[3.3.1]-nonanes by the reaction of 2-hydroxychalcones with 4-hydroxy-2(1H)-quinolinones/4-hydroxy-2(1H)-pyridinones in refluxing n-PrOH is described. The quinolinone fragment can be converted into the corresponding N-alkylated quinolinones and O-alkylated quinolines by the alkylation reaction. All the unknown compounds are characterized by means of 1H NMR, 13C NMR, IR and HRMS. The structures and configurations of 6-phenyl-2, 12-dihydro-1H-6, 12-methanobenzo[7, 8] [1, 3]dioxocino[5, 4-c]pyri-din-1-one (3r) and 1-isopropoxy-8-phenyl-14H-8, 14-methanobenzo[7, 8] [1, 3]dioxocino[5, 4-c]quinoline (6c) are further confirmed by X-ray single crystal diffraction analysis.
An efficient and stereoselective synthesis of quinolinone-and pyridinone-fused 2, 8-dioxabicyclo[3.3.1]-nonanes by the reaction of 2-hydroxychalcones with 4-hydroxy-2(1H)-quinolinones/4-hydroxy-2(1H)-pyridinones in refluxing n-PrOH is described. The quinolinone fragment can be converted into the corresponding N-alkylated quinolinones and O-alkylated quinolines by the alkylation reaction. All the unknown compounds are characterized by means of 1H NMR, 13C NMR, IR and HRMS. The structures and configurations of 6-phenyl-2, 12-dihydro-1H-6, 12-methanobenzo[7, 8] [1, 3]dioxocino[5, 4-c]pyri-din-1-one (3r) and 1-isopropoxy-8-phenyl-14H-8, 14-methanobenzo[7, 8] [1, 3]dioxocino[5, 4-c]quinoline (6c) are further confirmed by X-ray single crystal diffraction analysis.
2017, 37(3): 675-682
doi: 10.6023/cjoc201610018
Abstract:
The antitumor activity research of N-(thiazol-2-yl) amide derivatives has been the focus of scholars. Physiologi-cally active substances containing amines widely exist in nature. A series of novel N-(4-(t-butyl)-5-benzylthiazol-2-yl) aminoacetamides were synthesized, and their structures were confirmed by 1H NMR, 13C NMR and elemental analysis. These compounds were evaluated for their in vitro anticancer activity on A549, Hela and MCF-7 cells. Most of the investigated compounds exhibited broad-spectrum antitumor activity. Compound 1t displayed significant activity against Hela cancer cells with IC50 value of (6.4±2.2) μmol/L. The AO/EB staining and cell cycle experiments were carried out on the preferred com-pound 1t. The result showed that compound 1t could significantly induce apoptosis of tumor cells and arrest the Hela cells in the S phase.
The antitumor activity research of N-(thiazol-2-yl) amide derivatives has been the focus of scholars. Physiologi-cally active substances containing amines widely exist in nature. A series of novel N-(4-(t-butyl)-5-benzylthiazol-2-yl) aminoacetamides were synthesized, and their structures were confirmed by 1H NMR, 13C NMR and elemental analysis. These compounds were evaluated for their in vitro anticancer activity on A549, Hela and MCF-7 cells. Most of the investigated compounds exhibited broad-spectrum antitumor activity. Compound 1t displayed significant activity against Hela cancer cells with IC50 value of (6.4±2.2) μmol/L. The AO/EB staining and cell cycle experiments were carried out on the preferred com-pound 1t. The result showed that compound 1t could significantly induce apoptosis of tumor cells and arrest the Hela cells in the S phase.
2017, 37(3): 683-690
doi: 10.6023/cjoc201610023
Abstract:
Our previous studies have found that diaryl-β-lactam derivative (S)-4-(3-hydroxy-4-methoxyphenyl)-3-methylene-1-(3, 4, 5-trimethoxyphenyl) azetidin-2-one (3a) possesses potent antitumor activity and its mechanism of action was confirmed as a tubulin aggregation inhibitor. In this paper, 22 novel analogs were synthesized through modifications of the phenolic hydroxyl group in B ring of compound 3a. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS data. The inhibition against proliferation of A2780, MDA-MB-231, SKOV-3 and Hela cells were tested by thiazolyl blue tetrazolium bromide (MTT) assay, and the bioassay results demonstrated that most of these derivatives showed good anti-proliferative activities. Among them, (S)-1-(3, 4, 5-trimethoxyphenyl)-4-(3-(4-nitrobenzoyloxyl)-4-methoxyphenyl)-3-meth-ylene-azetidin-2-one (5n) exhibited most potent activities against the above four cancer cells with the corresponding IC50 values of 0.055, 0.105, 0.084 and 0.102 μmol/L, respectively, indicating that these type of compounds merit further investigation.
Our previous studies have found that diaryl-β-lactam derivative (S)-4-(3-hydroxy-4-methoxyphenyl)-3-methylene-1-(3, 4, 5-trimethoxyphenyl) azetidin-2-one (3a) possesses potent antitumor activity and its mechanism of action was confirmed as a tubulin aggregation inhibitor. In this paper, 22 novel analogs were synthesized through modifications of the phenolic hydroxyl group in B ring of compound 3a. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS data. The inhibition against proliferation of A2780, MDA-MB-231, SKOV-3 and Hela cells were tested by thiazolyl blue tetrazolium bromide (MTT) assay, and the bioassay results demonstrated that most of these derivatives showed good anti-proliferative activities. Among them, (S)-1-(3, 4, 5-trimethoxyphenyl)-4-(3-(4-nitrobenzoyloxyl)-4-methoxyphenyl)-3-meth-ylene-azetidin-2-one (5n) exhibited most potent activities against the above four cancer cells with the corresponding IC50 values of 0.055, 0.105, 0.084 and 0.102 μmol/L, respectively, indicating that these type of compounds merit further investigation.
2017, 37(3): 691-697
doi: 10.6023/cjoc201608027
Abstract:
A palladium-catalyzed indole dearomative arylalkynylation via decarboxylative coupling of alkynyl carboxylic acids and alkyl-palladium intermediates has been developed, which provides a reliable approach to a serious of structural diversely 2, 3-disubstituted indolines bearing vicinal tertiary and quaternary stereocenters in moderate to good yields and excellent diastereoselectivities.
A palladium-catalyzed indole dearomative arylalkynylation via decarboxylative coupling of alkynyl carboxylic acids and alkyl-palladium intermediates has been developed, which provides a reliable approach to a serious of structural diversely 2, 3-disubstituted indolines bearing vicinal tertiary and quaternary stereocenters in moderate to good yields and excellent diastereoselectivities.
2017, 37(3): 698-703
doi: 10.6023/cjoc201609031
Abstract:
A series of novel benzothieno[3', 2':2, 3]pyrido[4, 5-d]thiazolo[3, 2-a]pyrimidinone derivatives are prepared via sulfamic acid-catalyzed Pictet-Spengler cyclization of 7-(3-amino-5-phenylaminothiazolo-2-yl) thiazolo[3, 2-a]pyrimidin-5-one, which in turn were obtained from the Thorpe-Ziegler isomerization of 7-(chloromethyl) thiazolo[3, 2-a]pyrimidin-5-one with 2-mercaptobenzonitrile. The method was characterized with raw material easy to get, mild reaction conditions, good yields and a facile and efficient synthetic method of novel fused pyrimidines.
A series of novel benzothieno[3', 2':2, 3]pyrido[4, 5-d]thiazolo[3, 2-a]pyrimidinone derivatives are prepared via sulfamic acid-catalyzed Pictet-Spengler cyclization of 7-(3-amino-5-phenylaminothiazolo-2-yl) thiazolo[3, 2-a]pyrimidin-5-one, which in turn were obtained from the Thorpe-Ziegler isomerization of 7-(chloromethyl) thiazolo[3, 2-a]pyrimidin-5-one with 2-mercaptobenzonitrile. The method was characterized with raw material easy to get, mild reaction conditions, good yields and a facile and efficient synthetic method of novel fused pyrimidines.
2017, 37(3): 704-710
doi: 10.6023/cjoc201607013
Abstract:
The six novel N, O-chelated pyridine-BF2 complexes (2a~2f) were successfully obtained by a facile two-step synthesis from 2-amino-pyridine derivatives. All compounds synthesized were fully characterized by 1H NMR, 13C NMR, 19F NMR, IR, ESI-MS and X-ray diffraction analysis. It was found that complexes 2b, 2c, 2e and 2f, in which electron-donating groups were substituted on p-positions of the phenyl ring (or 6-positions of the pyridine ring) exhibit a structured absorption at 360~420 nm (λabs=368, 400, 365, 418 nm) with a large extinction coefficient, such as 28760, 51980, 25250, 40750 L·mol-1·cm-1, respectively. In sharp contrast, the complexes 2a and 2d with a relatively neutral group (H for 2a) or an electron-withdrawing group (COOMe for 2d) on the p-position of the phenyl ring gave the absorption (λabs) blue shifted to 340 and 337 nm. Meanwhile, the intramolecular charge transfer (ICT) could be detected for complexes 2b, 2c, 2e and 2f, whose emission bands bathochromic shift significantly and emission intensities decreased with increasing the solvent polarities. Additionally, similar to most boron-dipyrromethene derivatives (BODIPYs) and their derivatives, this pyridine-BF2 complex exhibited faint photoluminescence in the solid state. In order to better illustrate intramolecular charge transfer in 2b, 2c, 2e and 2f, theoretical calculations were carried out. Therefore, these experimental facts and theoretical calculations support our proposed ICT mechanism in the novel boron fluoride complexes 2b, 2c, 2e and 2f, and reveal that substituent groups have a significant in-fluence on optical properties. The investigations of novel pyridine-BF2 complexes will provide favorable foundation and theo-retical support for the further development of ICT-based fluorescent dyes and their applications.
The six novel N, O-chelated pyridine-BF2 complexes (2a~2f) were successfully obtained by a facile two-step synthesis from 2-amino-pyridine derivatives. All compounds synthesized were fully characterized by 1H NMR, 13C NMR, 19F NMR, IR, ESI-MS and X-ray diffraction analysis. It was found that complexes 2b, 2c, 2e and 2f, in which electron-donating groups were substituted on p-positions of the phenyl ring (or 6-positions of the pyridine ring) exhibit a structured absorption at 360~420 nm (λabs=368, 400, 365, 418 nm) with a large extinction coefficient, such as 28760, 51980, 25250, 40750 L·mol-1·cm-1, respectively. In sharp contrast, the complexes 2a and 2d with a relatively neutral group (H for 2a) or an electron-withdrawing group (COOMe for 2d) on the p-position of the phenyl ring gave the absorption (λabs) blue shifted to 340 and 337 nm. Meanwhile, the intramolecular charge transfer (ICT) could be detected for complexes 2b, 2c, 2e and 2f, whose emission bands bathochromic shift significantly and emission intensities decreased with increasing the solvent polarities. Additionally, similar to most boron-dipyrromethene derivatives (BODIPYs) and their derivatives, this pyridine-BF2 complex exhibited faint photoluminescence in the solid state. In order to better illustrate intramolecular charge transfer in 2b, 2c, 2e and 2f, theoretical calculations were carried out. Therefore, these experimental facts and theoretical calculations support our proposed ICT mechanism in the novel boron fluoride complexes 2b, 2c, 2e and 2f, and reveal that substituent groups have a significant in-fluence on optical properties. The investigations of novel pyridine-BF2 complexes will provide favorable foundation and theo-retical support for the further development of ICT-based fluorescent dyes and their applications.
2017, 37(3): 711-719
doi: 10.6023/cjoc201609029
Abstract:
Azulene is noteworthy for its deep blue color with a large dipole moment. Compared to other unsaturated aromatic hydrocarbons, azulenes show unique photophysical and electrical properties. Herein, two isomers of 1, 4, 5, 8-naphthalene diimide (NDI) endcapped with ethynylazulene units (1 and 2) are presented, which are capped with five-membered and seven-membered rings of azulene moieties, respectively. It is interesting that these two compounds show remarkably different physicochemical properties, thermal stabilities and organic field-effect transistors (OFET) performance resulting from the different connections of an electron-rich five-membered ring and an electron-poor seven-membered ring. Density functional theory (DFT) calculations reveal that the lowest unoccupied molecular orbital (LUMO) energy of 2 (endcapped with 6-ethynylalzulene) is lower than that of 1 (endcapped with 2-ethynylalzulene), and 2 makes the electrons of LUMO more delocalized, which favor the overlap of LUMO between molecules, thus to obtain higher mobility for 2. OFETs based on thin films of these two isomers were fabricated with conventional spin-coated techniques. Under nitrogen atmosphere, 1 and 2 show n-type semiconducting properties with electron mobilities of up to 0.022 and 0.16 cm2·V-1·s-1, respectively, which is consistent with the DFT results.
Azulene is noteworthy for its deep blue color with a large dipole moment. Compared to other unsaturated aromatic hydrocarbons, azulenes show unique photophysical and electrical properties. Herein, two isomers of 1, 4, 5, 8-naphthalene diimide (NDI) endcapped with ethynylazulene units (1 and 2) are presented, which are capped with five-membered and seven-membered rings of azulene moieties, respectively. It is interesting that these two compounds show remarkably different physicochemical properties, thermal stabilities and organic field-effect transistors (OFET) performance resulting from the different connections of an electron-rich five-membered ring and an electron-poor seven-membered ring. Density functional theory (DFT) calculations reveal that the lowest unoccupied molecular orbital (LUMO) energy of 2 (endcapped with 6-ethynylalzulene) is lower than that of 1 (endcapped with 2-ethynylalzulene), and 2 makes the electrons of LUMO more delocalized, which favor the overlap of LUMO between molecules, thus to obtain higher mobility for 2. OFETs based on thin films of these two isomers were fabricated with conventional spin-coated techniques. Under nitrogen atmosphere, 1 and 2 show n-type semiconducting properties with electron mobilities of up to 0.022 and 0.16 cm2·V-1·s-1, respectively, which is consistent with the DFT results.
2017, 37(3): 720-725
doi: 10.6023/cjoc201609033
Abstract:
An efficient and practical N-iodosuccinimide-promoted regioselective arylsulfenylation of imidazo[1, 2-a]pyridines with disulfides has been developed to afford functionalized 3-sulfenylimidazo[1, 2-a]pyridines heterocycles in moderate to good yields. Their structures were confirmed by IR, 1H NMR, 13C NMR and HRMS. Furthermore, this method has the advantages of mild reaction conditions, broad substrates scope and environmentally benign. Notably, the current methodology could also be conveniently applied to the synthesis of thioarylated naturally occurring biologically active frameworks.
An efficient and practical N-iodosuccinimide-promoted regioselective arylsulfenylation of imidazo[1, 2-a]pyridines with disulfides has been developed to afford functionalized 3-sulfenylimidazo[1, 2-a]pyridines heterocycles in moderate to good yields. Their structures were confirmed by IR, 1H NMR, 13C NMR and HRMS. Furthermore, this method has the advantages of mild reaction conditions, broad substrates scope and environmentally benign. Notably, the current methodology could also be conveniently applied to the synthesis of thioarylated naturally occurring biologically active frameworks.
2017, 37(3): 726-730
doi: 10.6023/cjoc201612004
Abstract:
A novel rhodamine-based probe L was synthesized and characterized. The results showed that probe L acted as a fluorescent enhancement probe for Cr3+, Fe3+ and Al3+ recognition in CH3OH/H2O (V:V=8:2, c(Tris)=10 mmol/L, pH=7.2). L is highly selective to trivalent ions Cr3+, Fe3+ and Al3+ over other monovalent or divalent ions. Detection limits of probe L for Cr3+, Fe3+ and Al3+ are 2.1×10-4, 2.3×10-4 and 4.4×10-4 mol/L, respectively, which make it have potentially application value in Cr3+, Fe3+ and Al3+ detection in various water samples.
A novel rhodamine-based probe L was synthesized and characterized. The results showed that probe L acted as a fluorescent enhancement probe for Cr3+, Fe3+ and Al3+ recognition in CH3OH/H2O (V:V=8:2, c(Tris)=10 mmol/L, pH=7.2). L is highly selective to trivalent ions Cr3+, Fe3+ and Al3+ over other monovalent or divalent ions. Detection limits of probe L for Cr3+, Fe3+ and Al3+ are 2.1×10-4, 2.3×10-4 and 4.4×10-4 mol/L, respectively, which make it have potentially application value in Cr3+, Fe3+ and Al3+ detection in various water samples.
2017, 37(3): 731-738
doi: 10.6023/cjoc201610017
Abstract:
To develop isopimaric acid derivatives with high bioactivity, fifteen acyl (amide) thiourea derivatives containing isopimaric acid skeleton were synthesized and confirmed by FT-IR, 1H NMR, 13C NMR and HRMS or elemental analysis. All the compounds were evaluated for their antibacterial and anticancer activity. Most of the compounds showed siginificant inhibitory activity which was higher than that of isopiamric acid against the Candida Albicans. At the concentration of 100 μmol/L, many compounds exhibited pronounced inhibitory effects on human melanoma cells (A375) and prostatic carcinoma (PC-3) cell lines, especially compounds N-isopimaric acyl-N'-(3-methylphenyl) sulfourea (3c) and N-isopimaric acylamino-N'-(4-fluorophenyl) sulfourea (6b) have the best anticancer activity, both with the inhibitory rate of over 90%.
To develop isopimaric acid derivatives with high bioactivity, fifteen acyl (amide) thiourea derivatives containing isopimaric acid skeleton were synthesized and confirmed by FT-IR, 1H NMR, 13C NMR and HRMS or elemental analysis. All the compounds were evaluated for their antibacterial and anticancer activity. Most of the compounds showed siginificant inhibitory activity which was higher than that of isopiamric acid against the Candida Albicans. At the concentration of 100 μmol/L, many compounds exhibited pronounced inhibitory effects on human melanoma cells (A375) and prostatic carcinoma (PC-3) cell lines, especially compounds N-isopimaric acyl-N'-(3-methylphenyl) sulfourea (3c) and N-isopimaric acylamino-N'-(4-fluorophenyl) sulfourea (6b) have the best anticancer activity, both with the inhibitory rate of over 90%.
2017, 37(3): 739-745
doi: 10.6023/cjoc201611029
Abstract:
In order to find new cyanoacrylate lead compounds, a series of novel cyanoacrylates containing substituted pyridyl moiety were prepared by the method of active substructure combination. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and elemental analyses. Preliminary bioassay data displayed that in postemergence treatment 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino (2-methoxy) ethyl ester (7l) had 95% herbicidal activity against Brassica juncea at 1500 g/ha and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-[2-(2, 4-difluorophenoxy)]ethyl ester (7e), 7l and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-(2-ethoxy) ethyl ester (7m) showed 80%, 80% and 100% herbicidal activity against Stellaria media, respectively. Additionally, 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino[2-(2-fluorophenoxy)]ethyl ester (7b), 7l and 7m all exhibited 100% herbicidal activity against Chenopodium serotinum L. at 1500 g/ha.
In order to find new cyanoacrylate lead compounds, a series of novel cyanoacrylates containing substituted pyridyl moiety were prepared by the method of active substructure combination. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and elemental analyses. Preliminary bioassay data displayed that in postemergence treatment 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino (2-methoxy) ethyl ester (7l) had 95% herbicidal activity against Brassica juncea at 1500 g/ha and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-[2-(2, 4-difluorophenoxy)]ethyl ester (7e), 7l and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-(2-ethoxy) ethyl ester (7m) showed 80%, 80% and 100% herbicidal activity against Stellaria media, respectively. Additionally, 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino[2-(2-fluorophenoxy)]ethyl ester (7b), 7l and 7m all exhibited 100% herbicidal activity against Chenopodium serotinum L. at 1500 g/ha.
2017, 37(3): 746-752
doi: 10.6023/cjoc201607010
Abstract:
An efficient methodology to access of quinazoline derivatives by the reaction of carbodiimides and alcohol under basic conditions has been developed. This paper provides an attractive strategy for construction of the quinazoline compounds and other heterocyclic compounds in a high reaction yield by using simple starting materials in mild reaction conditions and short reaction time.
An efficient methodology to access of quinazoline derivatives by the reaction of carbodiimides and alcohol under basic conditions has been developed. This paper provides an attractive strategy for construction of the quinazoline compounds and other heterocyclic compounds in a high reaction yield by using simple starting materials in mild reaction conditions and short reaction time.
2017, 37(3): 753-758
doi: 10.6023/cjoc201610002
Abstract:
Glycerol is an abundantly generated biomass and conversion of this compound into useful chemicals is of significant industrial value. Hydrogenolysis of glycerol produces a series of C-3 alcohols, such as 1-propanol, 2-propanol, 1, 2-pro-panediol and 1, 3-propanediol (1, 3-PDO). Among these compounds, 1, 3-PDO is an important organic intermediate to synthesize poly-trimethylene-terephthalate. Therefore, synthesis of 1, 3-PDO through the selective hydrogenolysis of glycerol is a promising subject. Recently, during our investigations on the Pt/WO3/ZrO2-catalyzed glycerol hydrolysis, it was found that the acidity of the catalyst could be controlled by tungsten oxide content and the glycerol conversion was largely improved with high 1, 3-PDO selectivity. The technology largely improved the synthetic efficiency and is of potential industrial application value.
Glycerol is an abundantly generated biomass and conversion of this compound into useful chemicals is of significant industrial value. Hydrogenolysis of glycerol produces a series of C-3 alcohols, such as 1-propanol, 2-propanol, 1, 2-pro-panediol and 1, 3-propanediol (1, 3-PDO). Among these compounds, 1, 3-PDO is an important organic intermediate to synthesize poly-trimethylene-terephthalate. Therefore, synthesis of 1, 3-PDO through the selective hydrogenolysis of glycerol is a promising subject. Recently, during our investigations on the Pt/WO3/ZrO2-catalyzed glycerol hydrolysis, it was found that the acidity of the catalyst could be controlled by tungsten oxide content and the glycerol conversion was largely improved with high 1, 3-PDO selectivity. The technology largely improved the synthetic efficiency and is of potential industrial application value.
2017, 37(3): 759-766
doi: 10.6023/cjocx201607022
Abstract:
A emulsion crosslinking method to prepare oridonin-porphyrin-chitosan microspheres with oridonin and 5-p-(6-bromohexylaminophenyl)-10, 15, 20-triphenylporphyrin-chitosan (BHP-CS) is reported, which in turn was synthesized from 5-p-(6-bromo-hexylaminophenyl)-10, 15, 20-triphenylporphyrin (BHP) and chitosan. The porphyrin grafting rate of BHP-CS reached 30.80% on average, the drug loading rate and entrapment rate of the prepared microspheres reached 12.41% and 8.72% measured by HPLC, and the accumulated release rate was 81.74% in 48 h in vitro. The thiazolyl blue tetrazolium bromide (MTT) method was used to evaluate the photocytotoxicities of these derivatives against MCF-7 cells. The results revealed that oridonin-porphyrin-chitosan microspheres showed high photocytotoxicity in concentrations of 25, 50 and 100 μmol/mL against MCF-7 cells, and the inhibit ratio of MCF-7 cells under light irradiation for 30 min were (31.55±1.70)%, (71.03±0.76)% and (82.74±0.38)%, respectively.
A emulsion crosslinking method to prepare oridonin-porphyrin-chitosan microspheres with oridonin and 5-p-(6-bromohexylaminophenyl)-10, 15, 20-triphenylporphyrin-chitosan (BHP-CS) is reported, which in turn was synthesized from 5-p-(6-bromo-hexylaminophenyl)-10, 15, 20-triphenylporphyrin (BHP) and chitosan. The porphyrin grafting rate of BHP-CS reached 30.80% on average, the drug loading rate and entrapment rate of the prepared microspheres reached 12.41% and 8.72% measured by HPLC, and the accumulated release rate was 81.74% in 48 h in vitro. The thiazolyl blue tetrazolium bromide (MTT) method was used to evaluate the photocytotoxicities of these derivatives against MCF-7 cells. The results revealed that oridonin-porphyrin-chitosan microspheres showed high photocytotoxicity in concentrations of 25, 50 and 100 μmol/mL against MCF-7 cells, and the inhibit ratio of MCF-7 cells under light irradiation for 30 min were (31.55±1.70)%, (71.03±0.76)% and (82.74±0.38)%, respectively.
2017, 37(3): 767-772
doi: 10.6023/cjoc201610005
Abstract:
3-Aminoestrogens are promising estrogen drugs. Traditional synthesis of the estrogens used estrone as a raw material, however, was not suitable for diversity-oriented synthesis. Herein, an efficient synthesis of 6-substitued-3-aminoestrogens from easily available 19-hydroxy-androst-4-ene-3, 17-dione via a tandem retro-aldol aromatization/intermolecular nucleophilic addition is presented. The method featured easily available reagents, simple operation and introduction of two substituents in one step.
3-Aminoestrogens are promising estrogen drugs. Traditional synthesis of the estrogens used estrone as a raw material, however, was not suitable for diversity-oriented synthesis. Herein, an efficient synthesis of 6-substitued-3-aminoestrogens from easily available 19-hydroxy-androst-4-ene-3, 17-dione via a tandem retro-aldol aromatization/intermolecular nucleophilic addition is presented. The method featured easily available reagents, simple operation and introduction of two substituents in one step.
