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2020 Volume 40 Issue 7
2020, 40(7): 1805-1813
doi: 10.6023/cjoc202003048
Abstract:
In recent years, the field of organic fluorine chemistry has developed rapidly. Fluorination and fluorine-containing functionalization reactions have attracted extensive attention of organic chemists due to their special physical and chemical properties. The introduction of fluorine-containing group into drug molecules can improve the biological activity of drug molecules. Trifluoromethoxy group has strong electron absorption and high lipophilicity, compounds containing trifluoromethoxy play an important role in the fields of medicine, pesticides and materials. In recent years, some innovative strategies have been used to synthesize compounds containing trifluoromethoxy group. This account mainly focuses on the research of trifluoromethoxy reaction in our group, and some challenges faced by trifluoromethoxy reaction.
In recent years, the field of organic fluorine chemistry has developed rapidly. Fluorination and fluorine-containing functionalization reactions have attracted extensive attention of organic chemists due to their special physical and chemical properties. The introduction of fluorine-containing group into drug molecules can improve the biological activity of drug molecules. Trifluoromethoxy group has strong electron absorption and high lipophilicity, compounds containing trifluoromethoxy play an important role in the fields of medicine, pesticides and materials. In recent years, some innovative strategies have been used to synthesize compounds containing trifluoromethoxy group. This account mainly focuses on the research of trifluoromethoxy reaction in our group, and some challenges faced by trifluoromethoxy reaction.
2020, 40(7): 1814-1822
doi: 10.6023/cjoc202004003
Abstract:
Pure organic luminescent supramolecular materials with either phosphorescence or fluorescence emission have become a hot research topic due to their low toxity, facile preparation and wide applications. In recent years, our group has designed several novel luminescent macromolecules, achieving tunable multi-color emission. For the construction of phosphorescent materials, heavy atoms such as bromine and iodine as well as other hetroatoms with lone pair electrons like oxygen were employed to facilitate the intersystem crossing (ISC) process of the luminophores while rigid environments were provided via host-guest interactions and polymerization to restrict molecular motions, which results in reduced nonradiative decay. Moreover, noncovalent interactions are stimuli responsive because of their dynamic nature. Therefore, host-guest interactions, along with other noncovalent interactions including hydrophobic effects, π-π stacking and multiple hydrogen bonding, were also used for adjusting the intensities and wavelengths of phosphorescence or fluorescence, achieving diverse luminescence properties that the luminophore itself does not possess. This account summarizes the above advances and proposes possible directions for further research, like not only improving quantum yields but also expanding the range of emission wavelength of organic phosphorescent materials and developing luminescent materials that can intelligently respond to external stimuli.
Pure organic luminescent supramolecular materials with either phosphorescence or fluorescence emission have become a hot research topic due to their low toxity, facile preparation and wide applications. In recent years, our group has designed several novel luminescent macromolecules, achieving tunable multi-color emission. For the construction of phosphorescent materials, heavy atoms such as bromine and iodine as well as other hetroatoms with lone pair electrons like oxygen were employed to facilitate the intersystem crossing (ISC) process of the luminophores while rigid environments were provided via host-guest interactions and polymerization to restrict molecular motions, which results in reduced nonradiative decay. Moreover, noncovalent interactions are stimuli responsive because of their dynamic nature. Therefore, host-guest interactions, along with other noncovalent interactions including hydrophobic effects, π-π stacking and multiple hydrogen bonding, were also used for adjusting the intensities and wavelengths of phosphorescence or fluorescence, achieving diverse luminescence properties that the luminophore itself does not possess. This account summarizes the above advances and proposes possible directions for further research, like not only improving quantum yields but also expanding the range of emission wavelength of organic phosphorescent materials and developing luminescent materials that can intelligently respond to external stimuli.
2020, 40(7): 1823-1834
doi: 10.6023/cjoc202003066
Abstract:
Host-guest interaction, as one of the most important behaviors in supramolecular self-assemblies, is often used to construct functional supramolecular materials. Based on host-guest interaction, it has become a hotspot in supramolecular chemistry by utilizing macrocyclic hosts and guests with aggregation-induced emission (AIE) properties as building blocks to construct supramolecular system, which can be widely used in drug delivery, cellular imaging, biosensing and so on. According to the origination of fluorescence effects of supramolecular assemblies, either from the host or guest molecules, the recent 5-year advances of AIE supramolecular self-assemblies based on host-guest interaction by utilizing macrocycles such as cyclodextrin, calixarene, cucurbituril, pillararene and other water-soluble host molecules are summarized, and their applications in the biomedical field are discussed.
Host-guest interaction, as one of the most important behaviors in supramolecular self-assemblies, is often used to construct functional supramolecular materials. Based on host-guest interaction, it has become a hotspot in supramolecular chemistry by utilizing macrocyclic hosts and guests with aggregation-induced emission (AIE) properties as building blocks to construct supramolecular system, which can be widely used in drug delivery, cellular imaging, biosensing and so on. According to the origination of fluorescence effects of supramolecular assemblies, either from the host or guest molecules, the recent 5-year advances of AIE supramolecular self-assemblies based on host-guest interaction by utilizing macrocycles such as cyclodextrin, calixarene, cucurbituril, pillararene and other water-soluble host molecules are summarized, and their applications in the biomedical field are discussed.
2020, 40(7): 1835-1846
doi: 10.6023/cjoc202003010
Abstract:
Ionic liquids (ILs) have been widely used because of their excellent physical and chemical properties, and environment-friendly properties. However, the high viscosity of ILs causes difficulties in post-reaction separation and low recyclability. As the combination of ionic liquids with a variety of solid materials, supported functional ILs (SFILs) have the coupled advantages of ILs and loaded materials. It has a wide range of applications in the field of catalysis because of its high recovery performance, green economy and high efficiency. This paper mainly reviews the recent achievements over SFILs in respects of the preparation of ILs supported on various carriers like magnetic nanoparticles, graphene oxide, molecular sieves, organic-metal skeleton etc., the applications as the heterogeneous catalysts to organic transformations, and the understanding of the catalytic mechanism.
Ionic liquids (ILs) have been widely used because of their excellent physical and chemical properties, and environment-friendly properties. However, the high viscosity of ILs causes difficulties in post-reaction separation and low recyclability. As the combination of ionic liquids with a variety of solid materials, supported functional ILs (SFILs) have the coupled advantages of ILs and loaded materials. It has a wide range of applications in the field of catalysis because of its high recovery performance, green economy and high efficiency. This paper mainly reviews the recent achievements over SFILs in respects of the preparation of ILs supported on various carriers like magnetic nanoparticles, graphene oxide, molecular sieves, organic-metal skeleton etc., the applications as the heterogeneous catalysts to organic transformations, and the understanding of the catalytic mechanism.
2020, 40(7): 1847-1859
doi: 10.6023/cjoc202002025
Abstract:
Selenium (Se) is an important trace element in life and has been associated with many diseases. Protein containing selenium has a wide range of biological effects, such as antioxidant, anti-inflammatory and promotes the production of thyroid hormone action. In the past few decades, selenium has attracted great attention because of its important role in biology, which is mainly attributed to the redox of Se elements and the properties of hard and soft protons. In recent years, with the development of chemical simulation technology, a large number of selenium-related fluorescent chemosensors have been developed to monitor physiological and pathological processes. Fluorescent chemosensors containing selenium materials, such as selenocysteine (Sec), hydrogen selenide and Se(Ⅳ) are reviewed. The development tendency of the sensing Se compounds is prospected.
Selenium (Se) is an important trace element in life and has been associated with many diseases. Protein containing selenium has a wide range of biological effects, such as antioxidant, anti-inflammatory and promotes the production of thyroid hormone action. In the past few decades, selenium has attracted great attention because of its important role in biology, which is mainly attributed to the redox of Se elements and the properties of hard and soft protons. In recent years, with the development of chemical simulation technology, a large number of selenium-related fluorescent chemosensors have been developed to monitor physiological and pathological processes. Fluorescent chemosensors containing selenium materials, such as selenocysteine (Sec), hydrogen selenide and Se(Ⅳ) are reviewed. The development tendency of the sensing Se compounds is prospected.
2020, 40(7): 1860-1873
doi: 10.6023/cjoc202002038
Abstract:
Functional groups are atoms or groups that determine the chemical properties of organic compounds. It often plays the role of guiding group in organic synthesis chemistry. Defunctionalization is the chemical transformation of a substrate with more functional groups into a compound with fewer functional groups, which has positive applications in solving environmental problems, resource shortage and biomass degradation. But due to the bond energy, heating, acid or base are often involved in defunctionalization. In recent years, defunctionalization has been moving toward a greener and more sustainable direction. Metal catalysis provides a new way for defunctionalization. The recent applications of different metal-mediated defunctionalization in organic synthesis and their mechanism are summarized.
Functional groups are atoms or groups that determine the chemical properties of organic compounds. It often plays the role of guiding group in organic synthesis chemistry. Defunctionalization is the chemical transformation of a substrate with more functional groups into a compound with fewer functional groups, which has positive applications in solving environmental problems, resource shortage and biomass degradation. But due to the bond energy, heating, acid or base are often involved in defunctionalization. In recent years, defunctionalization has been moving toward a greener and more sustainable direction. Metal catalysis provides a new way for defunctionalization. The recent applications of different metal-mediated defunctionalization in organic synthesis and their mechanism are summarized.
2020, 40(7): 1874-1890
doi: 10.6023/cjoc201912031
Abstract:
N-Methylation of amines and imines is one of the most important reactions for C-N bond formation. It is widely utilized for both laboratary research and industrial applications. Traditional methylation reactions involve the use of flammable, explosive and toxic starting materials. In contrast, newly developed methods have overcome this point and provide a mild strategy. In this transformation, C1 carbon source for the methyl group is important which determines the type of catalyst, reaction conditions and substrate scope. Herein, the research progress for the N-methylation of amines and imines is summarized based on different C1 carbon source.
N-Methylation of amines and imines is one of the most important reactions for C-N bond formation. It is widely utilized for both laboratary research and industrial applications. Traditional methylation reactions involve the use of flammable, explosive and toxic starting materials. In contrast, newly developed methods have overcome this point and provide a mild strategy. In this transformation, C1 carbon source for the methyl group is important which determines the type of catalyst, reaction conditions and substrate scope. Herein, the research progress for the N-methylation of amines and imines is summarized based on different C1 carbon source.
2020, 40(7): 1891-1900
doi: 10.6023/cjoc202003019
Abstract:
Due to the special gem-nitrogen structure, amidines are important compounds in the synthesis of nitrogen contaning products. As a class of featured amidines, the N-sulfonyl amidines are key intermediates in a number of pivatol organic syntheses, and thus ocuppy significant position in modern organic synthesis. In this context, the research advances on the synthesis of N-sulfonyl amidines are herein reviewed. Based on the key reaction features, the introduction covers the synthetic methods of enamination by tertiary enamine oxidation, amide activation, akyne-azide-amine three-component reaction, enamine carbon-carbon bond functionalization and other related reactions. It is expected that this review will provide guidelines for the reasearch work in related areas.
Due to the special gem-nitrogen structure, amidines are important compounds in the synthesis of nitrogen contaning products. As a class of featured amidines, the N-sulfonyl amidines are key intermediates in a number of pivatol organic syntheses, and thus ocuppy significant position in modern organic synthesis. In this context, the research advances on the synthesis of N-sulfonyl amidines are herein reviewed. Based on the key reaction features, the introduction covers the synthetic methods of enamination by tertiary enamine oxidation, amide activation, akyne-azide-amine three-component reaction, enamine carbon-carbon bond functionalization and other related reactions. It is expected that this review will provide guidelines for the reasearch work in related areas.
2020, 40(7): 1901-1911
doi: 10.6023/cjoc202001012
Abstract:
Trifluoromethyl is an important group, which is often used in pharmecuticals and agrochemicals. Quaternary carbon centers are widely existed in natural products and synthetic compounds. Recently, the construction of molecules containing trifluoromethylated quaternary carbon centers has been developed rapidly. Starting with direct trifluoromethylation, new synthons and new reactions, the research progress of the synthesis of trifluoromethylated quaternary carbon centers is reviewed.
Trifluoromethyl is an important group, which is often used in pharmecuticals and agrochemicals. Quaternary carbon centers are widely existed in natural products and synthetic compounds. Recently, the construction of molecules containing trifluoromethylated quaternary carbon centers has been developed rapidly. Starting with direct trifluoromethylation, new synthons and new reactions, the research progress of the synthesis of trifluoromethylated quaternary carbon centers is reviewed.
2020, 40(7): 1912-1925
doi: 10.6023/cjoc201912044
Abstract:
Aryl and vinyl sulfides have attracted much attention from medical and organic chemists because they are prevalent in natural or bioactive molecules and other potential functional organic materials. Therefore, considerable efforts have been made for the construction of aryl and vinyl sulfides, among them transition metal-free direct C-H bond sulfenylation has developed rapidly and became an efficient and eco-friendly synthetic protocol. In recent years, many excellent research achievements were presented and a range of sulfenylated alkenes and arenes were synthesized using this strategy. The recent five-year progress in direct sulfenylation of C-H bond on alkenes and arenes under transition metal-free conditions is reviewed and the corresponding reaction mechanisms are discussed.
Aryl and vinyl sulfides have attracted much attention from medical and organic chemists because they are prevalent in natural or bioactive molecules and other potential functional organic materials. Therefore, considerable efforts have been made for the construction of aryl and vinyl sulfides, among them transition metal-free direct C-H bond sulfenylation has developed rapidly and became an efficient and eco-friendly synthetic protocol. In recent years, many excellent research achievements were presented and a range of sulfenylated alkenes and arenes were synthesized using this strategy. The recent five-year progress in direct sulfenylation of C-H bond on alkenes and arenes under transition metal-free conditions is reviewed and the corresponding reaction mechanisms are discussed.
2020, 40(7): 1926-1933
doi: 10.6023/cjoc202003004
Abstract:
An oxidative twofold sulfination of alcohol with Selectfluor as an efficient oxidant was developed. This reaction proceeded smoothly achieving the unprecedented sulfination transformation of varieties of diaryldisulfides and alcohols under simple conditions, affording the corresponding sulfinic esters in excellent yields. The current reaction provides a new and convenient strategy for the preparation of sulfinic esters.
An oxidative twofold sulfination of alcohol with Selectfluor as an efficient oxidant was developed. This reaction proceeded smoothly achieving the unprecedented sulfination transformation of varieties of diaryldisulfides and alcohols under simple conditions, affording the corresponding sulfinic esters in excellent yields. The current reaction provides a new and convenient strategy for the preparation of sulfinic esters.
2020, 40(7): 1941-1947
doi: 10.6023/cjoc202003034
Abstract:
Taking advantage of the special oxidation property of hypochlorite, two novel coumarin-type fluorescent probes C1 and C2 were synthesized for ClO- detection. Both probes could detect ClO- anions in aqueous solution efficiently with rapid switching-on fluorescent methods. Especially, probe C2 displayed dramatic enhancement in fluorescence emission spectra with the detection limit of 1.8×10-7 mol/L. In addition to its high selectivity for ClO- rather than other common anions and reactive oxygen species, C2 was successfully applied to the bioimaging in HeLa cells with 'turn-on' fluorescent methods. Moreover, probe C2 could be used for the analysis of ClO- levels in tap water and potentially in environmental samples.
Taking advantage of the special oxidation property of hypochlorite, two novel coumarin-type fluorescent probes C1 and C2 were synthesized for ClO- detection. Both probes could detect ClO- anions in aqueous solution efficiently with rapid switching-on fluorescent methods. Especially, probe C2 displayed dramatic enhancement in fluorescence emission spectra with the detection limit of 1.8×10-7 mol/L. In addition to its high selectivity for ClO- rather than other common anions and reactive oxygen species, C2 was successfully applied to the bioimaging in HeLa cells with 'turn-on' fluorescent methods. Moreover, probe C2 could be used for the analysis of ClO- levels in tap water and potentially in environmental samples.
2020, 40(7): 1934-1940
doi: 10.6023/cjoc202003042
Abstract:
As an important endogenous signaling molecule, hydrogen peroxide (H2O2) is involved in regulating many physiological and pathological processes. Ischemia-reperfusion can induce the production of large amount of endogenous hydrogen peroxide, which can cause seriously damage to cells and tissues. The fluorescent probe with aggregation induced emission can avoid the shortage of the aggregation caused quenching of conventional fluorophores. A H2O2 fluorescent probe with aggregation induced emission properties was designed and synthesized by using 4-vinylpyridinyl modified tetraphenylethylene as the fluorophore and phenylboronic acid as the H2O2 sensing group. The structure of the probe was characterized by NMR and HRMS. The recognition behaviors of the probe to H2O2 were investigated by the UV-Vis absorption and fluorescence spectra, and the results exhibit its good selectivity and high sensitivity to H2O2. The fluorescence off-on enhancement was ca. 100-fold and the detection limit was 6.9×10-8 mol/L. The reaction of the probe and H2O2 resulted in the H2O2-mediated oxidation of phenylboronic acid, followed by hydrolysis and 1, 6-elimination of p-quinone-methide to generate (E)-4-(4-(2, 2-bis(4-methoxyphenyl)-1-phenylvinyl)styryl)pyridine (TPE-Py), which was confirmed by 1H NMR. The results of confocal imaging indicated that the probe was cell-permeable and capable of visualization of endogenous H2O2 in oxygen glucose deprivation/reoxygenation (OGD/R) model HeLa cells and lipopolysaccharide-treated zebrafish.
As an important endogenous signaling molecule, hydrogen peroxide (H2O2) is involved in regulating many physiological and pathological processes. Ischemia-reperfusion can induce the production of large amount of endogenous hydrogen peroxide, which can cause seriously damage to cells and tissues. The fluorescent probe with aggregation induced emission can avoid the shortage of the aggregation caused quenching of conventional fluorophores. A H2O2 fluorescent probe with aggregation induced emission properties was designed and synthesized by using 4-vinylpyridinyl modified tetraphenylethylene as the fluorophore and phenylboronic acid as the H2O2 sensing group. The structure of the probe was characterized by NMR and HRMS. The recognition behaviors of the probe to H2O2 were investigated by the UV-Vis absorption and fluorescence spectra, and the results exhibit its good selectivity and high sensitivity to H2O2. The fluorescence off-on enhancement was ca. 100-fold and the detection limit was 6.9×10-8 mol/L. The reaction of the probe and H2O2 resulted in the H2O2-mediated oxidation of phenylboronic acid, followed by hydrolysis and 1, 6-elimination of p-quinone-methide to generate (E)-4-(4-(2, 2-bis(4-methoxyphenyl)-1-phenylvinyl)styryl)pyridine (TPE-Py), which was confirmed by 1H NMR. The results of confocal imaging indicated that the probe was cell-permeable and capable of visualization of endogenous H2O2 in oxygen glucose deprivation/reoxygenation (OGD/R) model HeLa cells and lipopolysaccharide-treated zebrafish.
2020, 40(7): 1948-1954
doi: 10.6023/cjoc202002019
Abstract:
To explore succinate dehydrogenase inhibitor with new structure, the excellent fungicide boscalid was chosen as a lead compound, and seventeen N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methyl-2-(methylthio)pyrimidine-5-carbox-amides (4a~4g) and N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methylthio)pyrimidine-5-carboxamides (4h~4q) were designed and synthesized. The structures of target compounds were characterized by 1H NMR, 13C NMR, and MALDI-TOF-MS. The in vitro bioassay showed that sixteen compounds possessed high fungicidal activity against S. sclerotiorum with more than 90% inhibitory rate at 50 μg/mL, and some compounds showed moderate activity against B. cinerea at the same dose with inhibitory rate in the range of 70%~84%. The molecular docking study revealed that four hydrogen bonds and one cation-π interaction were formed between N-[2-((3-fluoro-4-methylphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methyl-thio)pyrimidine-5-carboxamide (4p) and succinate dehydrogenase (SDH) enzyme.
To explore succinate dehydrogenase inhibitor with new structure, the excellent fungicide boscalid was chosen as a lead compound, and seventeen N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methyl-2-(methylthio)pyrimidine-5-carbox-amides (4a~4g) and N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methylthio)pyrimidine-5-carboxamides (4h~4q) were designed and synthesized. The structures of target compounds were characterized by 1H NMR, 13C NMR, and MALDI-TOF-MS. The in vitro bioassay showed that sixteen compounds possessed high fungicidal activity against S. sclerotiorum with more than 90% inhibitory rate at 50 μg/mL, and some compounds showed moderate activity against B. cinerea at the same dose with inhibitory rate in the range of 70%~84%. The molecular docking study revealed that four hydrogen bonds and one cation-π interaction were formed between N-[2-((3-fluoro-4-methylphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methyl-thio)pyrimidine-5-carboxamide (4p) and succinate dehydrogenase (SDH) enzyme.
2020, 40(7): 1955-1966
doi: 10.6023/cjoc202003028
Abstract:
Chiral phase transfer catalysts play extrememly important role in the construction of natural products, the core structures of chiral drugs, and functional chiral chemicals, therefore have attracted more and more attention in recent years. In this paper, the chiral resolution of biphenyl skeletons was achieved by utilizing the readily available (R)-α-methoxy benzene acetic acid as resolution agent. A series of new biphenyl type of phase transfer catalysts were designed and synthesized based on the optically pure C2-symmetric chiral biphenyl framework. These catalysts are readily applicable to asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester with excellent enantioselectivity (up to 96%) and yield (up to 97%). The structure-activity relationship study on these catalysts showed that the methylation of hydroxyl group at C2 and C2' position is favorable for the selectivity, introduction of tert-butyl group at C3 and C3' position is unfavorable to both selectivity and reactivity. The catalysts bearing 3, 4, 5-trifluorophenyl group or 3, 5-bis(trifluoromethyl)phenyl group at C5 and C5' position showed good reactivity and selectivity.
Chiral phase transfer catalysts play extrememly important role in the construction of natural products, the core structures of chiral drugs, and functional chiral chemicals, therefore have attracted more and more attention in recent years. In this paper, the chiral resolution of biphenyl skeletons was achieved by utilizing the readily available (R)-α-methoxy benzene acetic acid as resolution agent. A series of new biphenyl type of phase transfer catalysts were designed and synthesized based on the optically pure C2-symmetric chiral biphenyl framework. These catalysts are readily applicable to asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester with excellent enantioselectivity (up to 96%) and yield (up to 97%). The structure-activity relationship study on these catalysts showed that the methylation of hydroxyl group at C2 and C2' position is favorable for the selectivity, introduction of tert-butyl group at C3 and C3' position is unfavorable to both selectivity and reactivity. The catalysts bearing 3, 4, 5-trifluorophenyl group or 3, 5-bis(trifluoromethyl)phenyl group at C5 and C5' position showed good reactivity and selectivity.
2020, 40(7): 1967-1974
doi: 10.6023/cjoc201902036
Abstract:
In order to find efficient and low toxicity anti-tumor drugs, a series of novel 4-aminoquinazoline derivatives containing benzothiazole were designed and synthesized. And their antiproliferative activities against four human cancer cell lines[human breast cancer cell line (MCF-7), human gastric carcinoma cell line (MGC-803), human prostate cancer cell line (PC-3), human gastric carcinoma cell line (HGC-27)] were evaluated by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited good antiproliferative activities against the four human tumor cell lines. Among them, 2-((benzo[d]thiazol-2-ylmethyl)thio)-N-(3-chloro-4-fluorophenyl)-quinazolin-4-amine (13n) showed the best antiproliferative activity against MCF-7, MGC 803, PC-3 and HGC-27 cancer cell lines, with IC50 values of (6.01±0.54), (7.63±0.48), (6.16±0.34), (7.59±0.62) μmol·L-1, respectively. Its activity was better than the positive control gefitinib. Molecular docking showed that compound 13n could bind well with epidermal growth factor receptor (EGFR). In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.
In order to find efficient and low toxicity anti-tumor drugs, a series of novel 4-aminoquinazoline derivatives containing benzothiazole were designed and synthesized. And their antiproliferative activities against four human cancer cell lines[human breast cancer cell line (MCF-7), human gastric carcinoma cell line (MGC-803), human prostate cancer cell line (PC-3), human gastric carcinoma cell line (HGC-27)] were evaluated by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited good antiproliferative activities against the four human tumor cell lines. Among them, 2-((benzo[d]thiazol-2-ylmethyl)thio)-N-(3-chloro-4-fluorophenyl)-quinazolin-4-amine (13n) showed the best antiproliferative activity against MCF-7, MGC 803, PC-3 and HGC-27 cancer cell lines, with IC50 values of (6.01±0.54), (7.63±0.48), (6.16±0.34), (7.59±0.62) μmol·L-1, respectively. Its activity was better than the positive control gefitinib. Molecular docking showed that compound 13n could bind well with epidermal growth factor receptor (EGFR). In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.
2020, 40(7): 1975-1982
doi: 10.6023/cjoc202003013
Abstract:
A series of novel quinazolinone derivatives containing hydrazone structural units were designed and synthesized with isatoic anhydride as the starting material. All target compounds were characterized by 1H NMR, 13C NMR and HRMS. The preliminary antibacterial activity results showed that the compounds exhibited a certain inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), Pseudomonas syringae pv. actinidiae (Psa) and Xanthomonas axonopodis pv. citri (Xac). Among them, (E)-4-methyl-N'-(4-((3-methyl-4-oxo-3, 4-dihydroquinazolin-2-yl)methoxy)benzylidene)benzenesulfonohydrazi-de (G18), (E)-2-((4-((2-(2, 6-dichlorophenyl)hydrazono)methyl)phenoxy)methyl)-3-methylquinazolin-4(3H)-one (G12) and (E)-N'-(4-((3-methyl-4-oxo-3, 4-dihydroquinazolin-2-yl)methoxy)benzylidene)benzenesulfonohydrazide (G16) displayed better antibacterial activity against Xoo, Xac and Psa than the control drugs of bismerthiazol and thiediazole-copper, respectively. Notably, (E)-2-((4-((2-(3, 5-dichlorophenyl)hydrazono)methyl)phenoxy)methyl)-3-methylquinazolin-4(3H)-one (G5) displayed fine broad-spectrum antimicrobial activity against Xoo, Xac and Psa.
A series of novel quinazolinone derivatives containing hydrazone structural units were designed and synthesized with isatoic anhydride as the starting material. All target compounds were characterized by 1H NMR, 13C NMR and HRMS. The preliminary antibacterial activity results showed that the compounds exhibited a certain inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), Pseudomonas syringae pv. actinidiae (Psa) and Xanthomonas axonopodis pv. citri (Xac). Among them, (E)-4-methyl-N'-(4-((3-methyl-4-oxo-3, 4-dihydroquinazolin-2-yl)methoxy)benzylidene)benzenesulfonohydrazi-de (G18), (E)-2-((4-((2-(2, 6-dichlorophenyl)hydrazono)methyl)phenoxy)methyl)-3-methylquinazolin-4(3H)-one (G12) and (E)-N'-(4-((3-methyl-4-oxo-3, 4-dihydroquinazolin-2-yl)methoxy)benzylidene)benzenesulfonohydrazide (G16) displayed better antibacterial activity against Xoo, Xac and Psa than the control drugs of bismerthiazol and thiediazole-copper, respectively. Notably, (E)-2-((4-((2-(3, 5-dichlorophenyl)hydrazono)methyl)phenoxy)methyl)-3-methylquinazolin-4(3H)-one (G5) displayed fine broad-spectrum antimicrobial activity against Xoo, Xac and Psa.
2020, 40(7): 1983-1990
doi: 10.6023/cjoc201912033
Abstract:
Extracellular regulated protein kinase (ERK) is a key kinase in the development of cancer. 12 urea compounds containing morpholin rings were designed and synthesized in search of novel ERK inhibitors by using merging strategy. The structures of all compounds were confirmed by 1H NMR, 13C NMR and HRMS. ERK kinase activity and cell proliferation test results indicate that most of the target compounds have moderately inhibitory effects on human colorectal cancer cells SW480 and HCT-116, especially the IC50 of 1-(4-fluorobenzyl)-3-(5-(4-morpholinophenyl)pyridin-2-yl)urea (18f) reaches 0.36 and 0.55 μmol/L, respectively, and has low toxicity to normal cells L02 (>10 μmol/L). At the same time, 18f can inhibit ERK kinase activity (IC50=0.051 μmol/L) and phosphorylation level, but does not affect total ERK expression and upstream upstream activation of mitogen-activated extracellular signal-regulated kinase (MEK) activation. These research provides important reference for the further study of novel benzylpyridylurea ERK inhibitors.
Extracellular regulated protein kinase (ERK) is a key kinase in the development of cancer. 12 urea compounds containing morpholin rings were designed and synthesized in search of novel ERK inhibitors by using merging strategy. The structures of all compounds were confirmed by 1H NMR, 13C NMR and HRMS. ERK kinase activity and cell proliferation test results indicate that most of the target compounds have moderately inhibitory effects on human colorectal cancer cells SW480 and HCT-116, especially the IC50 of 1-(4-fluorobenzyl)-3-(5-(4-morpholinophenyl)pyridin-2-yl)urea (18f) reaches 0.36 and 0.55 μmol/L, respectively, and has low toxicity to normal cells L02 (>10 μmol/L). At the same time, 18f can inhibit ERK kinase activity (IC50=0.051 μmol/L) and phosphorylation level, but does not affect total ERK expression and upstream upstream activation of mitogen-activated extracellular signal-regulated kinase (MEK) activation. These research provides important reference for the further study of novel benzylpyridylurea ERK inhibitors.
2020, 40(7): 2008-2017
doi: 10.6023/cjoc202001030
Abstract:
Aiming at the problem that the catalyst can not be recovered during the construction of the C-S bond in the indole ring with sulfur powder as the sulfur source, 2-pyridinecarboxylic acid modified chitosan (PACS) catalyst with different type of copper was prepared, which was used to catalyze the three-component reaction of indole, sulfur powder and iodobenzene to prepare C-3 thioether-based indole in a one-pot method. The reaction yield is as high as 92%, and the substrate has good applicability. The most suitable catalyst[PACS@Cu(OAc)2] was characterized and analyzed by thermogravimetric analysis (TGA), scanning electron microscope(SEM), X-ray photoelectron spectroscopy(XPS), etc. It shows that the catalyst has the advantages of no additional ligand, easy separation and reusable.
Aiming at the problem that the catalyst can not be recovered during the construction of the C-S bond in the indole ring with sulfur powder as the sulfur source, 2-pyridinecarboxylic acid modified chitosan (PACS) catalyst with different type of copper was prepared, which was used to catalyze the three-component reaction of indole, sulfur powder and iodobenzene to prepare C-3 thioether-based indole in a one-pot method. The reaction yield is as high as 92%, and the substrate has good applicability. The most suitable catalyst[PACS@Cu(OAc)2] was characterized and analyzed by thermogravimetric analysis (TGA), scanning electron microscope(SEM), X-ray photoelectron spectroscopy(XPS), etc. It shows that the catalyst has the advantages of no additional ligand, easy separation and reusable.
2020, 40(7): 2018-2025
doi: 10.6023/cjoc202003035
Abstract:
Both organofluorine and organosilicon compounds are one of the most important types of high-tech product in elementorganic chemistry, and have been received much attetions in the past decades. Considering the imporatance of difluoroethanol moeity in pesticides, the development of a mild and efficient copper-catalyzed arylated etherification reaction of difluoroethanol is highly desirable. Herein, a mild and efficient method for the preparation of difluoroethyl aryl ethers was developed by the copper-catalyzed Ullmann-type arylated etherification reaction of aryl bromides or iodides with 2, 2-difluoroethanol. This reaction proceeds smoothly in the presence of CuI and 8-hydroxyquinoline/t-BuOK, and has a broad substrate scope. ESI-MS analysis supported the existence of LCu(Ⅲ)Ar(OR) species during this catalytic reaction. Further density functional theory (DFT) calculations suggest a proposed mechanism of arylated etherification reaction involving oxidative addition, followed by nucleophile substitution and reductive elimination would be rational.
Both organofluorine and organosilicon compounds are one of the most important types of high-tech product in elementorganic chemistry, and have been received much attetions in the past decades. Considering the imporatance of difluoroethanol moeity in pesticides, the development of a mild and efficient copper-catalyzed arylated etherification reaction of difluoroethanol is highly desirable. Herein, a mild and efficient method for the preparation of difluoroethyl aryl ethers was developed by the copper-catalyzed Ullmann-type arylated etherification reaction of aryl bromides or iodides with 2, 2-difluoroethanol. This reaction proceeds smoothly in the presence of CuI and 8-hydroxyquinoline/t-BuOK, and has a broad substrate scope. ESI-MS analysis supported the existence of LCu(Ⅲ)Ar(OR) species during this catalytic reaction. Further density functional theory (DFT) calculations suggest a proposed mechanism of arylated etherification reaction involving oxidative addition, followed by nucleophile substitution and reductive elimination would be rational.
2020, 40(7): 2026-2034
doi: 10.6023/cjoc202003002
Abstract:
An efficient tin-powder-promoted C-C coupling reaction of 3-aryl-3-hydroxy-2-oxindoles with allyl bromide was disclosed, which makes tin-powder-promoted reactions beyond 1, 2-addition to C=O or C=N double bounds, and provides a convenient and facile protocol for the synthesis of potentially bioactive 3, 3'-disubstituted-2-oxindoles in good to excellent yields. The method is highly efficient and environmentally benign with low cost and concise manipulation.
An efficient tin-powder-promoted C-C coupling reaction of 3-aryl-3-hydroxy-2-oxindoles with allyl bromide was disclosed, which makes tin-powder-promoted reactions beyond 1, 2-addition to C=O or C=N double bounds, and provides a convenient and facile protocol for the synthesis of potentially bioactive 3, 3'-disubstituted-2-oxindoles in good to excellent yields. The method is highly efficient and environmentally benign with low cost and concise manipulation.
2020, 40(7): 2035-2044
doi: 10.6023/cjoc202002039
Abstract:
A novel synthetic methodology was developed and a series of pyrano[2, 3-b]naphthoquinone derivatives were designed and synthesized in excellent yields. Most of these compounds showed effective anti-AChE activities and high selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Among them, (2-Amino-4-(3-cyanophenyl)-5, 10-dioxo-5, 10-dihydro-4H-benzo[g]chromene-3-carbonitrile) (3n) was significantly potent, with an IC50 value of 1.22 μmol/L for AChE, which was 164-fold higher than butyrylcholinesterase (BuChE) in vitro. Moreover, molecular modeling provides valuable information for understanding the potency and selectivity of this kind of compounds for AChE. Consequently, these potent and highly selective AChE inhibitors are potential leads for development of the drug for treatment of Alzheimer's disease.
A novel synthetic methodology was developed and a series of pyrano[2, 3-b]naphthoquinone derivatives were designed and synthesized in excellent yields. Most of these compounds showed effective anti-AChE activities and high selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Among them, (2-Amino-4-(3-cyanophenyl)-5, 10-dioxo-5, 10-dihydro-4H-benzo[g]chromene-3-carbonitrile) (3n) was significantly potent, with an IC50 value of 1.22 μmol/L for AChE, which was 164-fold higher than butyrylcholinesterase (BuChE) in vitro. Moreover, molecular modeling provides valuable information for understanding the potency and selectivity of this kind of compounds for AChE. Consequently, these potent and highly selective AChE inhibitors are potential leads for development of the drug for treatment of Alzheimer's disease.
2020, 40(7): 2045-2050
doi: 10.6023/cjoc202001025
Abstract:
Synthesis of N-alkyl indoles via 2, 3-dicyano-5, 6-dichlorobenzoquinone (DDQ) mediated intramolecular oxidative decarboxylative aromatization of N-alkylindoline-2-carboxylic acids is reported. The good compatibility of this process leads to the development of a mild and metal-free one-pot synthesis of N-alkyl indoles from alkyl halides and indoline carboxylic acid. The one-pot three-component synthesis of 1, 4-bis((1H-indol-1-yl)methyl)benzene is also disclosed in satisfied yields.
Synthesis of N-alkyl indoles via 2, 3-dicyano-5, 6-dichlorobenzoquinone (DDQ) mediated intramolecular oxidative decarboxylative aromatization of N-alkylindoline-2-carboxylic acids is reported. The good compatibility of this process leads to the development of a mild and metal-free one-pot synthesis of N-alkyl indoles from alkyl halides and indoline carboxylic acid. The one-pot three-component synthesis of 1, 4-bis((1H-indol-1-yl)methyl)benzene is also disclosed in satisfied yields.
2020, 40(7): 2051-2061
doi: 10.6023/cjoc202003037
Abstract:
A novel gold(Ⅰ)-catalyzed glycosylation method was described to synthesize C-vinyl-rhamnopyranoside derivatives using stable propargylic carboxylates and 3, 4-di-O-acetyl-L-rhamnal as starting materials, based on the tandem intermolecular 1, 3-acyloxy migration/Ferrier rearrangement. The C-glycosylation process has been verified by O18 isotopic labeling experiment, and the absolute configuration of synthesized products was determined by X-ray single crystal diffraction. The cytotoxic activity was investigated by methyl thiazolyl tetrazolium (MTT). It indicates that product 3i has strong inhibitory effect on human gastric cancer cells HGC-27 with IC50 18.29 μmol·L-1. The described synthetic method was outstanding with easy-to-operate, high diastereoselectivity, and mild reaction condition.
A novel gold(Ⅰ)-catalyzed glycosylation method was described to synthesize C-vinyl-rhamnopyranoside derivatives using stable propargylic carboxylates and 3, 4-di-O-acetyl-L-rhamnal as starting materials, based on the tandem intermolecular 1, 3-acyloxy migration/Ferrier rearrangement. The C-glycosylation process has been verified by O18 isotopic labeling experiment, and the absolute configuration of synthesized products was determined by X-ray single crystal diffraction. The cytotoxic activity was investigated by methyl thiazolyl tetrazolium (MTT). It indicates that product 3i has strong inhibitory effect on human gastric cancer cells HGC-27 with IC50 18.29 μmol·L-1. The described synthetic method was outstanding with easy-to-operate, high diastereoselectivity, and mild reaction condition.
2020, 40(7): 2062-2070
doi: 10.6023/cjoc202003008
Abstract:
γ-Valerolactone (GVL) is an important biomass platform molecule, it can be converted into high value-added chemicals and fuel, which has important application prospects. This article describes a method for the synthesis of hydroxyamides and pyrrolidones from GVL and amine compounds by reductive amination/cyclization reactions under mild conditions using zirconium-based Lewis acid catalysts Zr-P-O and ZrOCl2·8H2O, respectively. In particular, a moderately high product yield can be obtained with the absence of a solvent. This method further lays the foundation for the application research of GVL.
γ-Valerolactone (GVL) is an important biomass platform molecule, it can be converted into high value-added chemicals and fuel, which has important application prospects. This article describes a method for the synthesis of hydroxyamides and pyrrolidones from GVL and amine compounds by reductive amination/cyclization reactions under mild conditions using zirconium-based Lewis acid catalysts Zr-P-O and ZrOCl2·8H2O, respectively. In particular, a moderately high product yield can be obtained with the absence of a solvent. This method further lays the foundation for the application research of GVL.
2020, 40(7): 2071-2077
doi: 10.6023/cjoc202003016
Abstract:
A based-free 5-exo-dig aza-cyclization of N-methoxyl-2-alkynylbenzamides in water is reported for the synthesis of various N-methoxylisoindolin-1-ones. The transformation proceeds smoothly with high efficiency and good functional group tolerance. In the process, it is believed that N-methoxyl protecting group serves as "molecular base" to facilitate the formation of amide nitrogen anion. Interestingly, by increasing reaction temperature, a series of N-free-isoindolin-1-ones were also obtained.
A based-free 5-exo-dig aza-cyclization of N-methoxyl-2-alkynylbenzamides in water is reported for the synthesis of various N-methoxylisoindolin-1-ones. The transformation proceeds smoothly with high efficiency and good functional group tolerance. In the process, it is believed that N-methoxyl protecting group serves as "molecular base" to facilitate the formation of amide nitrogen anion. Interestingly, by increasing reaction temperature, a series of N-free-isoindolin-1-ones were also obtained.
2020, 40(7): 2078-2085
doi: 10.6023/cjoc202002007
Abstract:
A visible-light-induced oxidative cyclization of N-propargylanilines with arylsulfonylhydrazides was developed using tert-butyl hydroperoxide as oxidant. This transformation offers a straightforward route to 3-sulfonated quinoline derivatives with good functional group tolerance, good to excellent yields and high regio-selectivity.
A visible-light-induced oxidative cyclization of N-propargylanilines with arylsulfonylhydrazides was developed using tert-butyl hydroperoxide as oxidant. This transformation offers a straightforward route to 3-sulfonated quinoline derivatives with good functional group tolerance, good to excellent yields and high regio-selectivity.
2020, 40(7): 2086-2093
doi: 10.6023/cjoc202003058
Abstract:
Sterically bulky amino magnesium methyl complex, LMgCH3(THF)2 (L＝NAr(SiMe3), Ar＝4, 2, 6-Me(CHPh2)2- C6H2) has been employed as an efficient precatalyst for the deoxygenate hydroboration of a variety of aromatic and aliphatic acids with pinacolborane (HBpin) under mild reaction condition. Additionally, chemoselective hydroboration of carboxylic acids over esters was also achieved under the standard conditions. Two plausible reaction mechanisms were proposed based on the density functional theory (DFT) calculations and stoichiometric reactions.
Sterically bulky amino magnesium methyl complex, LMgCH3(THF)2 (L＝NAr(SiMe3), Ar＝4, 2, 6-Me(CHPh2)2- C6H2) has been employed as an efficient precatalyst for the deoxygenate hydroboration of a variety of aromatic and aliphatic acids with pinacolborane (HBpin) under mild reaction condition. Additionally, chemoselective hydroboration of carboxylic acids over esters was also achieved under the standard conditions. Two plausible reaction mechanisms were proposed based on the density functional theory (DFT) calculations and stoichiometric reactions.
2020, 40(7): 1991-1998
doi: 10.6023/cjoc202003020
Abstract:
Catalyzed by supported palladium nanoparticles, an ortho-directed sulfonylation reaction between 2-phenylpyri-dine and arylsulfonyl chlorides has been developed. The full oxidation-state change of palladium was detected in the X-ray photoelectron spectroscopy (XPS) analysis of the supported palladium nanoparticles catalyst before and after reaction, which confirmed that Pd-catalyzed ortho-directed sulfonylation reaction was performed via a PdⅡ/IV catalytic cycle instead of Pd0/Ⅱ. The hot filtration test and other tests of catalysts further confirmed the hypothesis. This report afforded the most straightforward approach to confirm the variation of valence of palladium in ortho-directed sulfonylation reaction.
Catalyzed by supported palladium nanoparticles, an ortho-directed sulfonylation reaction between 2-phenylpyri-dine and arylsulfonyl chlorides has been developed. The full oxidation-state change of palladium was detected in the X-ray photoelectron spectroscopy (XPS) analysis of the supported palladium nanoparticles catalyst before and after reaction, which confirmed that Pd-catalyzed ortho-directed sulfonylation reaction was performed via a PdⅡ/IV catalytic cycle instead of Pd0/Ⅱ. The hot filtration test and other tests of catalysts further confirmed the hypothesis. This report afforded the most straightforward approach to confirm the variation of valence of palladium in ortho-directed sulfonylation reaction.
2020, 40(7): 1999-2007
doi: 10.6023/cjoc202003029
Abstract:
A one-pot reaction of Michael/hemiketalization and Fridel-Crafts reaction of α-hydroxy aryl ketones and β, γ-unsaturated α-ketoamides has been developed. The process enables efficient synthesis of tetrahydrofuran spirooxindoles using chain substrates that do not contain oxindole and tetrahydrofuran skeletons. A spiro-carbon center, an oxindole ring and a tetrahydrofuran ring, are constructed in this process.
A one-pot reaction of Michael/hemiketalization and Fridel-Crafts reaction of α-hydroxy aryl ketones and β, γ-unsaturated α-ketoamides has been developed. The process enables efficient synthesis of tetrahydrofuran spirooxindoles using chain substrates that do not contain oxindole and tetrahydrofuran skeletons. A spiro-carbon center, an oxindole ring and a tetrahydrofuran ring, are constructed in this process.
2020, 40(7): 2094-2098
doi: 10.6023/cjoc202002028
Abstract:
A two-step one-pot procedure for the synthesis of amino alcohols mediated by 1, 3-dibromo-5, 5-dimethylhydantoin (DBH) in aqueous acetone solution was developed. Styrene derivatives were treated with DBH at room temperature for 0.5~2.0 h followed by the addition of amine, affording the corresponding amino alcohols in 64%~88% yields. Tulobuterol, a widely used β2-adrenergic agonist, was prepared by this protocol in gram scale with the yield of 77%.
A two-step one-pot procedure for the synthesis of amino alcohols mediated by 1, 3-dibromo-5, 5-dimethylhydantoin (DBH) in aqueous acetone solution was developed. Styrene derivatives were treated with DBH at room temperature for 0.5~2.0 h followed by the addition of amine, affording the corresponding amino alcohols in 64%~88% yields. Tulobuterol, a widely used β2-adrenergic agonist, was prepared by this protocol in gram scale with the yield of 77%.
2020, 40(7): 2099-2107
doi: 10.6023/cjoc202004028
Abstract:
An nickel-catalyzed aerobic cross-dehydrogenative coupling of N-aryl tetrahydroisoquinolines is presented. The catalytic system could tolerate various N-aryl tetrahydroquinoline derivatives and nucleophiles, and the target products could be obtained in good to excellent yields. Compared with reported methods, the protocol uses molecular oxygen as a sustainable oxidant, and provides an effective approach to the synthesis of tetrahydroisoquinoline derivatives under mild and practical conditions.
An nickel-catalyzed aerobic cross-dehydrogenative coupling of N-aryl tetrahydroisoquinolines is presented. The catalytic system could tolerate various N-aryl tetrahydroquinoline derivatives and nucleophiles, and the target products could be obtained in good to excellent yields. Compared with reported methods, the protocol uses molecular oxygen as a sustainable oxidant, and provides an effective approach to the synthesis of tetrahydroisoquinoline derivatives under mild and practical conditions.
Synthesis and Preliminary Exploration of Biological Activity of 3-Aryl-4-arylamine Methyl Isoxazoles
2020, 40(7): 2108-2113
doi: 10.6023/cjoc202003026
Abstract:
The synthesis of isoxazole derivatives has been paid much attention by organic synthetic chemists because isoxazoles usually exhibit good biological activity such as insecticidal and bactericidal activity. In this study, a series of 3-aryl-4-arylamine methyl isoxazole derivatives were synthesized from ethyl 3-arylisoxazole-4-carboxylate by reduction, bromination and substitution reaction. The synthesized compounds were identified by 1H NMR, 13C NMR and HRMS, and the preliminary bioactivity test results showed that some compounds obtained had good inhibitory effects anainst aphids and armyworms.
The synthesis of isoxazole derivatives has been paid much attention by organic synthetic chemists because isoxazoles usually exhibit good biological activity such as insecticidal and bactericidal activity. In this study, a series of 3-aryl-4-arylamine methyl isoxazole derivatives were synthesized from ethyl 3-arylisoxazole-4-carboxylate by reduction, bromination and substitution reaction. The synthesized compounds were identified by 1H NMR, 13C NMR and HRMS, and the preliminary bioactivity test results showed that some compounds obtained had good inhibitory effects anainst aphids and armyworms.
2020, 40(7): 2114-2119
doi: 10.6023/cjoc202002008
Abstract:
6α- and 6β-hydroxydeoxycholic acids[DCA-6α-ol (6) and DCA-6β-ol (7)] are recently identified important tertiary bile acids derived from deoxycholic acid (3) in human liver. A rapid and robust synthesis of DCA-6α-ol (6) and DCA-6β-ol (7) from cholic acid (1) in 10 steps involing the key Mukaiyama aldol condensation, ozone oxidative cleavage and SmI2 promoted reductive deoxygenation was conducted.
6α- and 6β-hydroxydeoxycholic acids[DCA-6α-ol (6) and DCA-6β-ol (7)] are recently identified important tertiary bile acids derived from deoxycholic acid (3) in human liver. A rapid and robust synthesis of DCA-6α-ol (6) and DCA-6β-ol (7) from cholic acid (1) in 10 steps involing the key Mukaiyama aldol condensation, ozone oxidative cleavage and SmI2 promoted reductive deoxygenation was conducted.
2020, 40(7): 2127-2134
doi: 10.6023/cjoc202003001
Abstract:
A series of novel N-(substitutedbenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidine (thio)ureas (11a~11q) were synthesized from α-methoxyl methyl acetate, ethyl formate and substituted benzoic acids by cyclization, Dimroth rearrangement and nucleophilic addition reactions. The structures of products were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The preliminary bioassay showed that most of the compounds displayed positive fungicidal activity at 50 mg·L-1. Among them, N-(2-chlorobenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidinethiourea (11m) exhibited an inhibition rate of 67.25% against B. cinerea. All compounds showed certain insect growth regulation activities against 2~3 instar culex larvae, in which seven compounds exhibited revised uneclosion rate higher than 70%. N-(4-methylbenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidinethiourea (11l) showed excellent insecticidal activity, which was equivalent to the control 5% (mass fraction) pyriproxyfen. The preliminary structure-activity relationship analysis showed that compounds with electron-withdrawing group on the phenyl ring showed higher fungicidal activities, while compounds with electron-donating group exhibited higher insect growth regulation activities. Benzoylureas displayed higher fungicidal activities and benzoylthioureas exhibited good insect growth regulation activities.
A series of novel N-(substitutedbenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidine (thio)ureas (11a~11q) were synthesized from α-methoxyl methyl acetate, ethyl formate and substituted benzoic acids by cyclization, Dimroth rearrangement and nucleophilic addition reactions. The structures of products were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The preliminary bioassay showed that most of the compounds displayed positive fungicidal activity at 50 mg·L-1. Among them, N-(2-chlorobenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidinethiourea (11m) exhibited an inhibition rate of 67.25% against B. cinerea. All compounds showed certain insect growth regulation activities against 2~3 instar culex larvae, in which seven compounds exhibited revised uneclosion rate higher than 70%. N-(4-methylbenzoyl)-N'-4, 7-dimethoxy-[1,2,4]triazolo[1, 5-c]pyrimidinethiourea (11l) showed excellent insecticidal activity, which was equivalent to the control 5% (mass fraction) pyriproxyfen. The preliminary structure-activity relationship analysis showed that compounds with electron-withdrawing group on the phenyl ring showed higher fungicidal activities, while compounds with electron-donating group exhibited higher insect growth regulation activities. Benzoylureas displayed higher fungicidal activities and benzoylthioureas exhibited good insect growth regulation activities.
2020, 40(7): 2135-2141
doi: 10.6023/cjoc202002034
Abstract:
The one-pot tandem protocol for the preparation of biaryl fluorosulfates from bromo phenols was developed. Using Pd/C as catalyst, K2CO3 as base and aqueous ethanol as solvent, the Suzuki reaction was carried out at room temperature, then SO2F2 gas was added to the mixture to afford biaryl fluorosulfates product. The intermediate was not isolated, and phosphine ligand and nitrogen protection were not required during the reaction, which made the protocol more convenient to operate. The one-pot protocol could tolerate a range of functional groups and provided a highest product yield up to 97.2% at room temperature. Furthermore, Pd/C catalyst could be recycled and reused three times without significant loss of catalytic activity
The one-pot tandem protocol for the preparation of biaryl fluorosulfates from bromo phenols was developed. Using Pd/C as catalyst, K2CO3 as base and aqueous ethanol as solvent, the Suzuki reaction was carried out at room temperature, then SO2F2 gas was added to the mixture to afford biaryl fluorosulfates product. The intermediate was not isolated, and phosphine ligand and nitrogen protection were not required during the reaction, which made the protocol more convenient to operate. The one-pot protocol could tolerate a range of functional groups and provided a highest product yield up to 97.2% at room temperature. Furthermore, Pd/C catalyst could be recycled and reused three times without significant loss of catalytic activity
2020, 40(7): 2148-2152
doi: 10.6023/cjoc201912037
Abstract:
A synthetic plan of bicyclo[5/6] key intermediate of cyathane is reported. All the involved reactions, such as nucleophilic substitution reaction, radical ring-closing reaction, Johnson-Claisen rearrangement and Grignard addition, were optimized for higher yields. The procedure provides a simple and efficient method for the synthesis of bicyclo-key intermediate of cyathane. It is expected to have wide applications in the synthesis of cyathane.
A synthetic plan of bicyclo[5/6] key intermediate of cyathane is reported. All the involved reactions, such as nucleophilic substitution reaction, radical ring-closing reaction, Johnson-Claisen rearrangement and Grignard addition, were optimized for higher yields. The procedure provides a simple and efficient method for the synthesis of bicyclo-key intermediate of cyathane. It is expected to have wide applications in the synthesis of cyathane.
2020, 40(7): 2120-2126
doi: 10.6023/cjoc202003021
Abstract:
3-(4'-Hydroxy-3'-methoxybenzyl)-2(5H)-furanone (1), a rare benzyl furanone derivate, and two new lignans (2 and 3) were isolated from the heartwood of Nothotsuga longibracteata, together with nineteen known lignans compounds. The structures and absolute configurations of the undescribed compounds were elucidated on the basis of HR-ESI-MS, 1D NMR, 2D NMR, and CD spectroscopies. The cytotoxic effects of the isolated new lignan compounds on three human tumour cell lines (A172, SHSY5Y, and Hela) were evaluated by methyl thiazolyl tetrazolium (MTT) assay. Their showed no cytotoxic activities at the concentration of 50 μmol/L. Gastrointestinal motility test of zebrafish showed that compound 3 has the function of promoting gastrointestinal motility of zebrafish to excrete Nile red at doses 8 and 24 μmol/L by means of acting on the cholinergic nervous system.
3-(4'-Hydroxy-3'-methoxybenzyl)-2(5H)-furanone (1), a rare benzyl furanone derivate, and two new lignans (2 and 3) were isolated from the heartwood of Nothotsuga longibracteata, together with nineteen known lignans compounds. The structures and absolute configurations of the undescribed compounds were elucidated on the basis of HR-ESI-MS, 1D NMR, 2D NMR, and CD spectroscopies. The cytotoxic effects of the isolated new lignan compounds on three human tumour cell lines (A172, SHSY5Y, and Hela) were evaluated by methyl thiazolyl tetrazolium (MTT) assay. Their showed no cytotoxic activities at the concentration of 50 μmol/L. Gastrointestinal motility test of zebrafish showed that compound 3 has the function of promoting gastrointestinal motility of zebrafish to excrete Nile red at doses 8 and 24 μmol/L by means of acting on the cholinergic nervous system.
2020, 40(7): 2142-2147
doi: 10.6023/cjoc202003032
Abstract:
N-Iodo-succininide (NIS)/K2S2O8 initiated C-C bond formation reaction through self-coupling of enamides has been reported. The environmental friendliness and high atom-economy of this transition-metal free radical pathway offers a useful and attractive strategy to nitrogen-containing quaternary carbon centers.
N-Iodo-succininide (NIS)/K2S2O8 initiated C-C bond formation reaction through self-coupling of enamides has been reported. The environmental friendliness and high atom-economy of this transition-metal free radical pathway offers a useful and attractive strategy to nitrogen-containing quaternary carbon centers.
2020, 40(7): 2153-2158
doi: 10.6023/cjoc202002014
Abstract:
A simple two-step, one-pot synthesis of 1, 2, 2-triiodovinyl derivatives from terminal alkynes using N-iodosuc-cinimide and iodine as precursors, activated with γ-aluminum oxide is developed. This approach resulted in moderate to excellent yields, good functional group tolerance and utilization of an inexpensive catalyst.
A simple two-step, one-pot synthesis of 1, 2, 2-triiodovinyl derivatives from terminal alkynes using N-iodosuc-cinimide and iodine as precursors, activated with γ-aluminum oxide is developed. This approach resulted in moderate to excellent yields, good functional group tolerance and utilization of an inexpensive catalyst.
2020, 40(7): 2161-2163
doi: 10.6023/cjoc202000038
Abstract:
2020, 40(7): 2164-2166
doi: 10.6023/cjoc202000039
Abstract:
2020, 40(7): 2167-2169
doi: 10.6023/cjoc202000040
Abstract:
2020, 40(7): 2170-2172
doi: 10.6023/cjoc202000041
Abstract:
2020, 40(7): 2173-2175
doi: 10.6023/cjoc202000042
Abstract:
2020, 40(7): 2176-2179
doi: 10.6023/cjoc202000043
Abstract:
2020, 40(7): 2180-2181
doi: 10.6023/cjoc202000044
Abstract:
2020, 40(7): 2182-2183
doi: 10.6023/cjoc202000045
Abstract:
