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2018 Volume 38 Issue 5
2018, 38(5): 983-998
doi: 10.6023/cjoc201711046
Abstract:
Nitrogen zole s-triazine derivatives display several biological activities such as antiproliferative, antioxidant, antiviral, antitumor and so on. Accordingly, much effort has been made towards the development of diverse synthetic methods for nitrogen zole s-triazines. The advancements in synthesis of nitrogen zole s-triazine compounds are summarized, including tetrazolo-s-triazines, triazolo-s-triazines and diazolo-s-triazines. At last the disadvantages of these synthetic methods are discussed and prospected to the future development.
Nitrogen zole s-triazine derivatives display several biological activities such as antiproliferative, antioxidant, antiviral, antitumor and so on. Accordingly, much effort has been made towards the development of diverse synthetic methods for nitrogen zole s-triazines. The advancements in synthesis of nitrogen zole s-triazine compounds are summarized, including tetrazolo-s-triazines, triazolo-s-triazines and diazolo-s-triazines. At last the disadvantages of these synthetic methods are discussed and prospected to the future development.
2018, 38(5): 999-1008
doi: 10.6023/cjoc201711037
Abstract:
The first radical cation salt (RCS) was prepared more than 100 years ago, and with the recent renaissance of radical chemistry, the RCS promoted organic transformations attrack extensively attention. In early research, RCS was mainly used to initiate single electron oxidation reactions, such as cycloaddition, fragmentation, rearrangement and so on. Recently, RCS was used to induce the aerobic oxidation of C—H bond, and achieved a series of direct functionalization of C—H bond. In this review, prominent examples from the recent literatures are organized on the basis of the different reactions enabled by RCS catalysis.
The first radical cation salt (RCS) was prepared more than 100 years ago, and with the recent renaissance of radical chemistry, the RCS promoted organic transformations attrack extensively attention. In early research, RCS was mainly used to initiate single electron oxidation reactions, such as cycloaddition, fragmentation, rearrangement and so on. Recently, RCS was used to induce the aerobic oxidation of C—H bond, and achieved a series of direct functionalization of C—H bond. In this review, prominent examples from the recent literatures are organized on the basis of the different reactions enabled by RCS catalysis.
2018, 38(5): 1009-1028
doi: 10.6023/cjoc201711043
Abstract:
Vinyl azides have been extensively studied in organic synthesis since 1910. As a series of important intermediates, vinyl azides have a wide range of applications in recent years, especially in the synthesis of heterocyclic compounds catalyzed by transition-metals. The progress of the construction of aza-heterocyclic compounds in the field of organic synthesis is reviewed.
Vinyl azides have been extensively studied in organic synthesis since 1910. As a series of important intermediates, vinyl azides have a wide range of applications in recent years, especially in the synthesis of heterocyclic compounds catalyzed by transition-metals. The progress of the construction of aza-heterocyclic compounds in the field of organic synthesis is reviewed.
2018, 38(5): 1029-1034
doi: 10.6023/cjoc201712010
Abstract:
Indole derivatives have been considered as "privileged scaffolds" in drug discovery since they are capable of binding many receptors with high affinity. 3-Indolecarboxylates are widespread structure motifs in many natural products and drug molecules, such as arbidol, tropisetron, PD 0298029, and grandilodine A, etc. Consequently, synthetic studies toward 3-indolecarboxylates have been reported in recent years. Elegant cyclization strategies have been developed via transition-metal catalyzed or transition-metal-free reactions, and direct functionalization at C-3 position for synthesis of ester functional groups was also extremely attractive. Based on our studies toward synthesis of 3-indolecarboxylates, the recent developments of synthesis of 3-indolecarboxylates by different synthetic methods in view of the types of substrates are reviewed.
Indole derivatives have been considered as "privileged scaffolds" in drug discovery since they are capable of binding many receptors with high affinity. 3-Indolecarboxylates are widespread structure motifs in many natural products and drug molecules, such as arbidol, tropisetron, PD 0298029, and grandilodine A, etc. Consequently, synthetic studies toward 3-indolecarboxylates have been reported in recent years. Elegant cyclization strategies have been developed via transition-metal catalyzed or transition-metal-free reactions, and direct functionalization at C-3 position for synthesis of ester functional groups was also extremely attractive. Based on our studies toward synthesis of 3-indolecarboxylates, the recent developments of synthesis of 3-indolecarboxylates by different synthetic methods in view of the types of substrates are reviewed.
2018, 38(5): 1035-1051
doi: 10.6023/cjoc201709037
Abstract:
The detection and fluorescent identification of some substances such as sLea/x in vivo can provide important reference for the diagnosis, treatment and prognosis of disease, molecular tracing and further research on the mechanism of related diseases. Therefore, the development and discovery of high selectivity and high sensitivity chemsensors is of great value. Due to the special structure, phenyl boronic acid compounds could interact and bind with sugar, catecholamine containing catechol structure, fluoride or alkali cyanide. So boronic acids could be develeped as fluorescence sensors selectively for related substances, while have the advantages of high selectivity, high efficiency, rapid analysis and so on. In recent years, boronic acid has been functioned with new materials such as nanoparticles and quantum dots to design novel sensors for better performance. In this paper, the recent progress in the study of boronic acid compounds in sensors is reviewed.
The detection and fluorescent identification of some substances such as sLea/x in vivo can provide important reference for the diagnosis, treatment and prognosis of disease, molecular tracing and further research on the mechanism of related diseases. Therefore, the development and discovery of high selectivity and high sensitivity chemsensors is of great value. Due to the special structure, phenyl boronic acid compounds could interact and bind with sugar, catecholamine containing catechol structure, fluoride or alkali cyanide. So boronic acids could be develeped as fluorescence sensors selectively for related substances, while have the advantages of high selectivity, high efficiency, rapid analysis and so on. In recent years, boronic acid has been functioned with new materials such as nanoparticles and quantum dots to design novel sensors for better performance. In this paper, the recent progress in the study of boronic acid compounds in sensors is reviewed.
2018, 38(5): 1052-1064
doi: 10.6023/cjoc201710018
Abstract:
N-Substituted 1, 2, 3-triazole is an important structural unit in organic chemistry, and has widely utilized in organic synthesis, medicinal chemistry and material science. The chemistry of N1-substituted 1, 2, 3-triazoles has attracted much attention from organic chemists, while the synthesis and application of their N2-isomers have been far less explored. The recent progress on the research field of N2-alkyl, allyl, propargyl, vinyl, aryl substituted 1, 2, 3-triazoles since year 2000 is summarized, including some research of our group. The content is classified by different synthetic methods, such as selective functionalization of 1, 2, 3-triazoles and oxidative cyclization of bisarylhydrazones or azobenzenes.
N-Substituted 1, 2, 3-triazole is an important structural unit in organic chemistry, and has widely utilized in organic synthesis, medicinal chemistry and material science. The chemistry of N1-substituted 1, 2, 3-triazoles has attracted much attention from organic chemists, while the synthesis and application of their N2-isomers have been far less explored. The recent progress on the research field of N2-alkyl, allyl, propargyl, vinyl, aryl substituted 1, 2, 3-triazoles since year 2000 is summarized, including some research of our group. The content is classified by different synthetic methods, such as selective functionalization of 1, 2, 3-triazoles and oxidative cyclization of bisarylhydrazones or azobenzenes.
2018, 38(5): 1065-1084
doi: 10.6023/cjoc201711013
Abstract:
Artificial foldamers were constructed by non-covalent interactions to mimic the structures of biomacromolecules, such as proteins and DNA, which is conducive to a better understanding of the chemical processes at the molecular level in nature. The significant advances in foldamers render it become one of the most important topics in supramolecular chemistry. Coordination bond is widely used in the self-assembly process due to its bond strength and diverse geometry. In this article, we summarize a few types of metal-coordination helical folding systems, including single helicate, double helicates, triple helicates, quadruple helicates and cyclic helicates, and their folding behaviors and structural reconfiguration in the coordination process.
Artificial foldamers were constructed by non-covalent interactions to mimic the structures of biomacromolecules, such as proteins and DNA, which is conducive to a better understanding of the chemical processes at the molecular level in nature. The significant advances in foldamers render it become one of the most important topics in supramolecular chemistry. Coordination bond is widely used in the self-assembly process due to its bond strength and diverse geometry. In this article, we summarize a few types of metal-coordination helical folding systems, including single helicate, double helicates, triple helicates, quadruple helicates and cyclic helicates, and their folding behaviors and structural reconfiguration in the coordination process.
2018, 38(5): 1085-1106
doi: 10.6023/cjoc201709014
Abstract:
As a type of potential photovoltaic device, dye-sensitized solar cells (DSSCs) have attracted tremendous attention due to its high cost-effective and simple manufacturing process. In the device, dye molecules attach on the metal oxide surface via chemical bonds between anchor substituents and metal oxide substrate, realizing the light harvesting and photoelectron injection. Traditionally, carboxylic acids, such as benzoic acid and cyanoacrylic acid groups, have been widely utilized as the anchor groups in DSSCs. However, the detachment of dye molecules from metal oxide surface during device operation and consequent long-term stability issues cannot be ignored. Therefore, in view of durability of DSSCs in practical application, various anchor groups with a better ability to graft on the metal oxide have been explored. Several robust anchor groups in recent years and corresponding photovoltaic parameters are reviewed and the relationship between molecular structures and device performance is also discussed. The research progress of anchoring groups in photocatalytic hydrogen and quantum dot sensitized solar cells (QDSSCs) is also examined.
As a type of potential photovoltaic device, dye-sensitized solar cells (DSSCs) have attracted tremendous attention due to its high cost-effective and simple manufacturing process. In the device, dye molecules attach on the metal oxide surface via chemical bonds between anchor substituents and metal oxide substrate, realizing the light harvesting and photoelectron injection. Traditionally, carboxylic acids, such as benzoic acid and cyanoacrylic acid groups, have been widely utilized as the anchor groups in DSSCs. However, the detachment of dye molecules from metal oxide surface during device operation and consequent long-term stability issues cannot be ignored. Therefore, in view of durability of DSSCs in practical application, various anchor groups with a better ability to graft on the metal oxide have been explored. Several robust anchor groups in recent years and corresponding photovoltaic parameters are reviewed and the relationship between molecular structures and device performance is also discussed. The research progress of anchoring groups in photocatalytic hydrogen and quantum dot sensitized solar cells (QDSSCs) is also examined.
2018, 38(5): 1107-1118
doi: 10.6023/cjoc201711027
Abstract:
Stimuli-responsive supramolecular drug delivery systems (SDDSs) self-assembled by supra-amphiphiles have received tremendous attentions in cancer therapy due to various advantages of SDDSs, such as enhanced drug bioavailability, prolonged blood circulation and retention time, improved drug stability and so on. The construction of smart supramolecular drug delivery systems based on the different structural characteristics of macrocyclic compounds are reviewed and their recent applications in anti-cancer drug delivery are described. Advantages and drawbacks of the current supramolecular drug delivery systems are also discussed, along with the opportunities and challenges in future.
Stimuli-responsive supramolecular drug delivery systems (SDDSs) self-assembled by supra-amphiphiles have received tremendous attentions in cancer therapy due to various advantages of SDDSs, such as enhanced drug bioavailability, prolonged blood circulation and retention time, improved drug stability and so on. The construction of smart supramolecular drug delivery systems based on the different structural characteristics of macrocyclic compounds are reviewed and their recent applications in anti-cancer drug delivery are described. Advantages and drawbacks of the current supramolecular drug delivery systems are also discussed, along with the opportunities and challenges in future.
2018, 38(5): 1119-1125
doi: 10.6023/cjoc201710017
Abstract:
With saddle-shaped cyclooctatetrathiophene (COTh) and 1, 3, 5-triazine as building blocks, three derivatives bearing one, two and three COTh units are synthesized via Kumada-typed reaction. Theoretical calculations indicate that the two absorption peaks in long wavelength region are derived from intramolecular charge transfer (CT) absorption. 2, 4- Di(methoxyl)-6-(5, 8, 11-tris(trimethylsilyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (1), 2-meth- oxyl-4, 6-di(5, 8, 11-tris(trimethyl-silyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (2) and 2, 4, 6-tris- (5, 8, 11-tris(trimethylsilyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (3) exhibit intramolecular charge transfer (ICT) state emission peaked in region of 560~570 nm in solution at room temperature, and give both local emission of COTh peaked at 400 nm and ICT state emission peaked in region of 480~500 nm in rigid solution at 77 K. In tetrahydrofuran (THF)-H2O binary solvent system, compounds 1, 2 and 3 show typical aggregation induced emissions (AIE), which may be controlled by mechanism of restriction of intramolecular rotations (RIR) and restriction of intramolecular vibration (RIV). Crystal structure of 1 shows that intramolecular two rings of triazine and its linked thiophene are planar. There are strong C-C interactions between intermolecular rings of triazine and thiophene, which restrict the intramolecular rotation between triazine and thiophene rings. Such intermolecular C-C interactions are helpful to decrease the process of non-irradiative decay and increase AIE emission.
With saddle-shaped cyclooctatetrathiophene (COTh) and 1, 3, 5-triazine as building blocks, three derivatives bearing one, two and three COTh units are synthesized via Kumada-typed reaction. Theoretical calculations indicate that the two absorption peaks in long wavelength region are derived from intramolecular charge transfer (CT) absorption. 2, 4- Di(methoxyl)-6-(5, 8, 11-tris(trimethylsilyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (1), 2-meth- oxyl-4, 6-di(5, 8, 11-tris(trimethyl-silyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (2) and 2, 4, 6-tris- (5, 8, 11-tris(trimethylsilyl)cycloocta [1, 2-b:4, 3-b':5, 6-b":8, 7-b'"]tetrathiophen-2-yl)-1, 3, 5-triazine (3) exhibit intramolecular charge transfer (ICT) state emission peaked in region of 560~570 nm in solution at room temperature, and give both local emission of COTh peaked at 400 nm and ICT state emission peaked in region of 480~500 nm in rigid solution at 77 K. In tetrahydrofuran (THF)-H2O binary solvent system, compounds 1, 2 and 3 show typical aggregation induced emissions (AIE), which may be controlled by mechanism of restriction of intramolecular rotations (RIR) and restriction of intramolecular vibration (RIV). Crystal structure of 1 shows that intramolecular two rings of triazine and its linked thiophene are planar. There are strong C-C interactions between intermolecular rings of triazine and thiophene, which restrict the intramolecular rotation between triazine and thiophene rings. Such intermolecular C-C interactions are helpful to decrease the process of non-irradiative decay and increase AIE emission.
2018, 38(5): 1126-1137
doi: 10.6023/cjoc201709046
Abstract:
A series of novel imidazole derivatives containing indole or carbazole unit were efficiently synthesized via one-pot reaction of benzil/9, 10-phenanthraquinone, indole-3-carbaldehyde/carbazole-3-carbaldehyde and ammonium acetate utilizing glacial acetic acid as solvent and catalyst. The effects of selection and amount of solvents, molar ratio of the reagents, and temperature on the reactions have been surveyed. The photophysical properties of the synthesized products were also investigated, and two compounds possessing structural characteristics and pH-sensitive were selected as pH fluorescent probes. Furthermore, the fluorescence imaging of MCF-7 cells in different pH environments in the presence of the probe 2-(9-benzyl- 9H-carbazol-3-yl)-1H-4, 5-diphenylimidazole (2d) or 2-(9-benzyl-9H-carbazol-3-yl)-1H-phenanthro [9, 10-d]imidazole (4) was detected, and the results revealed that the two probes show promising potential to be used in detecting pH changes in living cells as pH fluorescent probes.
A series of novel imidazole derivatives containing indole or carbazole unit were efficiently synthesized via one-pot reaction of benzil/9, 10-phenanthraquinone, indole-3-carbaldehyde/carbazole-3-carbaldehyde and ammonium acetate utilizing glacial acetic acid as solvent and catalyst. The effects of selection and amount of solvents, molar ratio of the reagents, and temperature on the reactions have been surveyed. The photophysical properties of the synthesized products were also investigated, and two compounds possessing structural characteristics and pH-sensitive were selected as pH fluorescent probes. Furthermore, the fluorescence imaging of MCF-7 cells in different pH environments in the presence of the probe 2-(9-benzyl- 9H-carbazol-3-yl)-1H-4, 5-diphenylimidazole (2d) or 2-(9-benzyl-9H-carbazol-3-yl)-1H-phenanthro [9, 10-d]imidazole (4) was detected, and the results revealed that the two probes show promising potential to be used in detecting pH changes in living cells as pH fluorescent probes.
2018, 38(5): 1138-1146
doi: 10.6023/cjoc201712039
Abstract:
The application of [4+2] cycloaddition reaction of tetrazine with cyclooctyne in the construction of pyridazine structure with axial chirality was studied. The inverse electronic demand Diels-Alder reaction of tetrazine bearing bulky groups with macrocyclic tension's cyclooctyne could take place under catalyst-free conditions in dichloromethane. The reaction underwent a six-membered bridged transition state, gently release a molecule of nitrogen to get axial chiral pyridazine structure. The transformation of the reaction can be determined by the change of color. The reaction could get potential axial chiral pyridazine structure with high yiled (95%) under mild conditions.
The application of [4+2] cycloaddition reaction of tetrazine with cyclooctyne in the construction of pyridazine structure with axial chirality was studied. The inverse electronic demand Diels-Alder reaction of tetrazine bearing bulky groups with macrocyclic tension's cyclooctyne could take place under catalyst-free conditions in dichloromethane. The reaction underwent a six-membered bridged transition state, gently release a molecule of nitrogen to get axial chiral pyridazine structure. The transformation of the reaction can be determined by the change of color. The reaction could get potential axial chiral pyridazine structure with high yiled (95%) under mild conditions.
2018, 38(5): 1147-1154
doi: 10.6023/cjoc201712017
Abstract:
A series of morpholine nucleoside analogues were synthesized starting from ribonucleosides, and then the morpholine nucleoside sulfonamide derivatives were obtained by treated with N-acetylsulfanilyl chloride. The obtained compounds were confirmed by HRMS, 1H NMR and 13C NMR spectral analysis. The bovine kidney cells infected with bovine viral diarrhea virus (BVDV) were used as models to screen the antiviral activity of the target compounds. But the results did not show desired potent antiviral activity.
A series of morpholine nucleoside analogues were synthesized starting from ribonucleosides, and then the morpholine nucleoside sulfonamide derivatives were obtained by treated with N-acetylsulfanilyl chloride. The obtained compounds were confirmed by HRMS, 1H NMR and 13C NMR spectral analysis. The bovine kidney cells infected with bovine viral diarrhea virus (BVDV) were used as models to screen the antiviral activity of the target compounds. But the results did not show desired potent antiviral activity.
2018, 38(5): 1177-1184
doi: 10.6023/cjoc201712001
Abstract:
Two versions of carbon-14 labelled dufulin, diethyl ((2-fluorophenyl)((4-methyl [phenyl-U-14C6]benzo [d]thiazol- 2-yl)amino)methyl)phosphonate (2) and diethyl ((2-fluorophenyl)((4-methylbenzo [d]thiazol-2-yl)amino) [14C]methyl)phos- phonate (3), were separately synthesized from barium [14C]carbonate via ethyne cyclotrimerization, carboxylation and methylation of benzene ring, amination, cyclization, nucleophilic substitution, Grignard reaction, oxidation, reduction reaction, etc. The labelled products were obtained independently after reverse phase high-performance liquid chromatography (RP-HPLC) purification in the overall radiochemical/chemical yield of 31% and 67% and identified by using 1H NMR and flow scintillation analyzer/photo-diode array/mass spectrometry (HPLC-FSA/PDA/MS). Their technical data was determined by using TLC-ⅡA (isotope imaging analysis), HPLC-LSC (liquid scintillation counter), HPLC-FSA/PDA/MS and LSC, respectively. The result demonstrates that radiochemical/chemical purity of 2 and 3 is more than 98% and the specific activities of 2 and 3 are 25.5 and 55.5 mCi/mmol, respectively. The carbon-14 labelled products can be used as radiotracer in the study on its metabolism, residue and environmental behavior by employing radioisotope tracing techniques.
Two versions of carbon-14 labelled dufulin, diethyl ((2-fluorophenyl)((4-methyl [phenyl-U-14C6]benzo [d]thiazol- 2-yl)amino)methyl)phosphonate (2) and diethyl ((2-fluorophenyl)((4-methylbenzo [d]thiazol-2-yl)amino) [14C]methyl)phos- phonate (3), were separately synthesized from barium [14C]carbonate via ethyne cyclotrimerization, carboxylation and methylation of benzene ring, amination, cyclization, nucleophilic substitution, Grignard reaction, oxidation, reduction reaction, etc. The labelled products were obtained independently after reverse phase high-performance liquid chromatography (RP-HPLC) purification in the overall radiochemical/chemical yield of 31% and 67% and identified by using 1H NMR and flow scintillation analyzer/photo-diode array/mass spectrometry (HPLC-FSA/PDA/MS). Their technical data was determined by using TLC-ⅡA (isotope imaging analysis), HPLC-LSC (liquid scintillation counter), HPLC-FSA/PDA/MS and LSC, respectively. The result demonstrates that radiochemical/chemical purity of 2 and 3 is more than 98% and the specific activities of 2 and 3 are 25.5 and 55.5 mCi/mmol, respectively. The carbon-14 labelled products can be used as radiotracer in the study on its metabolism, residue and environmental behavior by employing radioisotope tracing techniques.
2018, 38(5): 1193-1198
doi: 10.6023/cjoc201710035
Abstract:
A copper-promoted N-arylation of 8-acylaminoquinolines has been developed. The N-arylation of 8-acylaminoquinoline with triaryl bismuth generated the target products in moderate to high yields under 40 mol% Cu(OAc)2, 2.0 equiv. of NaHCO3 in 1, 4-dioxane at 100 ℃ for 12 h. The reaction is compatible with a wide range of quinoline substrates, which provides a new method for synthesis of N-arylamide compounds.
A copper-promoted N-arylation of 8-acylaminoquinolines has been developed. The N-arylation of 8-acylaminoquinoline with triaryl bismuth generated the target products in moderate to high yields under 40 mol% Cu(OAc)2, 2.0 equiv. of NaHCO3 in 1, 4-dioxane at 100 ℃ for 12 h. The reaction is compatible with a wide range of quinoline substrates, which provides a new method for synthesis of N-arylamide compounds.
2018, 38(5): 1199-1206
doi: 10.6023/cjoc201711011
Abstract:
Quinoline-2, 4-dione unit is present in many natural products and synthetic compounds along with a broad range of bioactivities. Herein, a new approach to the synthesis of quinoline-2, 4-diones is developed based on a methyl triflate (TfOMe)-promoted intramolecular Houben-Hoesch reaction of α, α-dialkyl substituted cyanoacetanilides. The broad substrate scope, simple operation and mild reaction conditions make this synthetic method very attractive.
Quinoline-2, 4-dione unit is present in many natural products and synthetic compounds along with a broad range of bioactivities. Herein, a new approach to the synthesis of quinoline-2, 4-diones is developed based on a methyl triflate (TfOMe)-promoted intramolecular Houben-Hoesch reaction of α, α-dialkyl substituted cyanoacetanilides. The broad substrate scope, simple operation and mild reaction conditions make this synthetic method very attractive.
2018, 38(5): 1207-1213
doi: 10.6023/cjoc201711036
Abstract:
A new approach for the synthesis of alkynyl sulfides and asymmetric disulfides with odorless, easy-to-handle sodium arylsulfiniates as the sulfur source in I2/PPh3 aqueous system has been developed. Compared with reported approaches, this protocol provides several merits including simple procedures, free of transition-metal catalysts and organic solvent, and high yields.
A new approach for the synthesis of alkynyl sulfides and asymmetric disulfides with odorless, easy-to-handle sodium arylsulfiniates as the sulfur source in I2/PPh3 aqueous system has been developed. Compared with reported approaches, this protocol provides several merits including simple procedures, free of transition-metal catalysts and organic solvent, and high yields.
2018, 38(5): 1214-1222
doi: 10.6023/cjoc201712019
Abstract:
Based on avermectin structure framework, a series of novel 4"-avermectin triazole derivatives containing amide unit were synthesized via the method of click reaction and amidation. The structures of target compounds were fully characterized by 1H NMR, 13C NMR and HRMS. The preliminary bioassay showed that the target compounds possessed certain insceticidal activities against Tetranychus cinnabarinus, Myzus persicae and Caenorhabditis elegans. At the concentration of 0.1 μg/mL, the lethal rates of 4"-(1-(4-(2-(4-chlorphenyl)-3-methylbutylamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11b) and 4"-(1-(4-chlorobenzoamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11e) against Tetranychus cinnabarinus were 83.5% and 81.2%, respectively, and the lethal rates of 4"-(1-(2-amido-3-methylphenylethylamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11i) against Myzus persicae (c=50 μg/mL) and Caenorhabditis elegans (c=1 μg/mL) were 86.4% and 74.6%, which were better than that of avermetcin B1a.
Based on avermectin structure framework, a series of novel 4"-avermectin triazole derivatives containing amide unit were synthesized via the method of click reaction and amidation. The structures of target compounds were fully characterized by 1H NMR, 13C NMR and HRMS. The preliminary bioassay showed that the target compounds possessed certain insceticidal activities against Tetranychus cinnabarinus, Myzus persicae and Caenorhabditis elegans. At the concentration of 0.1 μg/mL, the lethal rates of 4"-(1-(4-(2-(4-chlorphenyl)-3-methylbutylamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11b) and 4"-(1-(4-chlorobenzoamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11e) against Tetranychus cinnabarinus were 83.5% and 81.2%, respectively, and the lethal rates of 4"-(1-(2-amido-3-methylphenylethylamido)-1H-1, 2, 3-triazolyl)acetamido)avermectin B1a (11i) against Myzus persicae (c=50 μg/mL) and Caenorhabditis elegans (c=1 μg/mL) were 86.4% and 74.6%, which were better than that of avermetcin B1a.
2018, 38(5): 1223-1232
doi: 10.6023/cjoc201704028
Abstract:
Twenty-one novel 1, 3, 5-triazine-1H-pyrazole-triazolethiadiazole derivatives are designed and synthesized, in which the excellent pharmacological activitive pyrazole is used as key skeleton by connecting 1, 3, 5-triazine and introducing triazolothiadiazole. The structures of 21 target compounds are characterized by IR, 1H NMR and HRMS. The inhibitory activities of 21 novel target products against Cdc25B and PTP1B are evaluated. As a result, most of the target compounds exhibit excellent inhibitory activities. In the Cdc25B inhibitory activity test, 14 target compounds have higher inhibitory activities than the positive reference sodium orthovanadate, and they are expected to be potential of Cdc25B inhibitors. In the PTP1B inhibitory activity test, 9 target compounds have better inhibitory activities than the control oleanolic acid, and they are expected to be potential of PTP1B inhibitors.
Twenty-one novel 1, 3, 5-triazine-1H-pyrazole-triazolethiadiazole derivatives are designed and synthesized, in which the excellent pharmacological activitive pyrazole is used as key skeleton by connecting 1, 3, 5-triazine and introducing triazolothiadiazole. The structures of 21 target compounds are characterized by IR, 1H NMR and HRMS. The inhibitory activities of 21 novel target products against Cdc25B and PTP1B are evaluated. As a result, most of the target compounds exhibit excellent inhibitory activities. In the Cdc25B inhibitory activity test, 14 target compounds have higher inhibitory activities than the positive reference sodium orthovanadate, and they are expected to be potential of Cdc25B inhibitors. In the PTP1B inhibitory activity test, 9 target compounds have better inhibitory activities than the control oleanolic acid, and they are expected to be potential of PTP1B inhibitors.
2018, 38(5): 1233-1241
doi: 10.6023/cjoc201708027
Abstract:
Pyranocoumarin is an important kind of natural products, which has many biological activities and pharmacological effects, such as antitumor, anti-bacterial, anti-human immunodeficiency virus (HIV), anti-inflammatory, antioxidation, etc. Pyrimidine is another important nitrogen-containing heterocycles. Using the pharmacophore combination principle of drug design, it is possible to obtain lead compounds with better anticancer activities by puting pyranocoumarin and pyrimidine structures together. Therefore, pyranocoumarin which has cyanoenamine structure was synthesized by multicomponent reaction, taking 4-hydroxycoumarin, aromatic aldehyde, malononitrile as raw materials and 4-dimethylaminopyridine (DMAP) as catalyst. Then N, N-dimethyl formamidine derivatives were synthesized by treatment with dimethylformamide-dimethyl acetal. Finally 4-anilino substituted pyranocoumarin fused pyrimidines were synthesized by treatment with substituted anilines involving Dimroth rearrangement. The structures of target compounds were characterized by melting point, IR, 1H NMR, 13C NMR and elemental analysis. This method has some advantages with short reaction time, mild reaction condition, simple operation, high yields and with no chromatographic separation procedure. All the title compounds were evaluated for anticancer activities in vitro against HL-60 cell lines and Hela human cervical cartcinoma cell lines. The results showed that 4-(4'-bromophenylamino)-5-(2', 3'-dichlorophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4k) and 4-(4'-bromo-phenylamino)-5-(4'-nitrophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4l) exhibited high activity against HL-60 with IC50 values of (11.3±0.3) and (10.8±0.2) μmol/L, and 4-(4'-chlorophenylamino)-5-(3', 4', 5'-trimethoxyphenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4g) and 4-(3'-chloro-4'-fluorophenylamino)-5-(3', 4', 5'-trimethoxy-phenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4h) exhibited high activity against Hela with IC50 value of (9.2±0.6) and (8.5±0.2) μmol/L.
Pyranocoumarin is an important kind of natural products, which has many biological activities and pharmacological effects, such as antitumor, anti-bacterial, anti-human immunodeficiency virus (HIV), anti-inflammatory, antioxidation, etc. Pyrimidine is another important nitrogen-containing heterocycles. Using the pharmacophore combination principle of drug design, it is possible to obtain lead compounds with better anticancer activities by puting pyranocoumarin and pyrimidine structures together. Therefore, pyranocoumarin which has cyanoenamine structure was synthesized by multicomponent reaction, taking 4-hydroxycoumarin, aromatic aldehyde, malononitrile as raw materials and 4-dimethylaminopyridine (DMAP) as catalyst. Then N, N-dimethyl formamidine derivatives were synthesized by treatment with dimethylformamide-dimethyl acetal. Finally 4-anilino substituted pyranocoumarin fused pyrimidines were synthesized by treatment with substituted anilines involving Dimroth rearrangement. The structures of target compounds were characterized by melting point, IR, 1H NMR, 13C NMR and elemental analysis. This method has some advantages with short reaction time, mild reaction condition, simple operation, high yields and with no chromatographic separation procedure. All the title compounds were evaluated for anticancer activities in vitro against HL-60 cell lines and Hela human cervical cartcinoma cell lines. The results showed that 4-(4'-bromophenylamino)-5-(2', 3'-dichlorophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4k) and 4-(4'-bromo-phenylamino)-5-(4'-nitrophenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4l) exhibited high activity against HL-60 with IC50 values of (11.3±0.3) and (10.8±0.2) μmol/L, and 4-(4'-chlorophenylamino)-5-(3', 4', 5'-trimethoxyphenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4g) and 4-(3'-chloro-4'-fluorophenylamino)-5-(3', 4', 5'-trimethoxy-phenyl)-chromene [3', 4':5, 6]pyrano [2, 3-d]pyrimidin-6-one (4h) exhibited high activity against Hela with IC50 value of (9.2±0.6) and (8.5±0.2) μmol/L.
2018, 38(5): 1242-1250
doi: 10.6023/cjoc201709022
Abstract:
A series of new acylthiourea derivatives 3 containing carbazole moity have been synthesized by the techniques of ultrasonic irradiation and solid-liquid phase transfer catalysis. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. This synthetic method has the advantages of short reaction time, simple operation and high yield. All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B). The results show that all the compounds 3 display significant inhibitory activities against Cdc25B, and partial target compounds 3 also show significant inhibitory activities against PTP1B. Among them, 1-(4-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3n) exhibits highest inhibitory activity against Cdc25B [IC50=(0.49±0.12) mg/mL] and 1-(2-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3l) displays highest inhibitory activity against PTP1B [IC50=(3.59±1.15) mg/mL]. It is noteworthy that compound 3n shows higher inhibitory activity against Cdc25B and PTP1B. The preliminary research results of molecular docking revealed the structural-activity of the inhibitors. The active compounds can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
A series of new acylthiourea derivatives 3 containing carbazole moity have been synthesized by the techniques of ultrasonic irradiation and solid-liquid phase transfer catalysis. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. This synthetic method has the advantages of short reaction time, simple operation and high yield. All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B). The results show that all the compounds 3 display significant inhibitory activities against Cdc25B, and partial target compounds 3 also show significant inhibitory activities against PTP1B. Among them, 1-(4-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3n) exhibits highest inhibitory activity against Cdc25B [IC50=(0.49±0.12) mg/mL] and 1-(2-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3l) displays highest inhibitory activity against PTP1B [IC50=(3.59±1.15) mg/mL]. It is noteworthy that compound 3n shows higher inhibitory activity against Cdc25B and PTP1B. The preliminary research results of molecular docking revealed the structural-activity of the inhibitors. The active compounds can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
2018, 38(5): 1251-1260
doi: 10.6023/cjoc201711045
Abstract:
The chiral triarylmethane frameworks are featured in many biologically important molecules. As a result, the synthesis of chiral triarylmethanes has received tremendous attention from the chemists. Herein, we reported the chiral phosphoric acid catalyzed dehydrative arylation of 3-indolylmethanols with tryptophols, leading to the efficient synthesis of a series of structurally diversified chiral bisindolyl-substituted triarylmethanes in moderate to good yields (up to 80% yield) with acceptable enantioselectivities (up to 88% ee). The chiral phosphoric acid played an important role not only in the dehydration of 3-indolylmethanols, but also in the control of enantioselectivity via hydrogen-bonding and ion-pairing interactions. The only byproduct was water, indicating that this catalytic asymmetric dehydrative arylation reaction was environment-friendly and in accordance with the requirements of green chemistry. In addition, the mild reaction condition and wide substrate scope of the reaction have successfully demonstrated the great potential of organocatalysis in the chiral triarylmethanes.
The chiral triarylmethane frameworks are featured in many biologically important molecules. As a result, the synthesis of chiral triarylmethanes has received tremendous attention from the chemists. Herein, we reported the chiral phosphoric acid catalyzed dehydrative arylation of 3-indolylmethanols with tryptophols, leading to the efficient synthesis of a series of structurally diversified chiral bisindolyl-substituted triarylmethanes in moderate to good yields (up to 80% yield) with acceptable enantioselectivities (up to 88% ee). The chiral phosphoric acid played an important role not only in the dehydration of 3-indolylmethanols, but also in the control of enantioselectivity via hydrogen-bonding and ion-pairing interactions. The only byproduct was water, indicating that this catalytic asymmetric dehydrative arylation reaction was environment-friendly and in accordance with the requirements of green chemistry. In addition, the mild reaction condition and wide substrate scope of the reaction have successfully demonstrated the great potential of organocatalysis in the chiral triarylmethanes.
2018, 38(5): 1155-1164
doi: 10.6023/cjoc201709049
Abstract:
The triethylamine catalyzed nucleophilic addition of 3, 5-dialkyl-4-nitroisoxazoles to trifluoromethyl ketones on water has been realized affording trifluoromethyl tertiary alcohol derivatives in 66%~99% yields. The products were easily transformed to the resulting alkenes by dehydration or acids by oxidation.
The triethylamine catalyzed nucleophilic addition of 3, 5-dialkyl-4-nitroisoxazoles to trifluoromethyl ketones on water has been realized affording trifluoromethyl tertiary alcohol derivatives in 66%~99% yields. The products were easily transformed to the resulting alkenes by dehydration or acids by oxidation.
2018, 38(5): 1165-1171
doi: 10.6023/cjoc201711028
Abstract:
In this paper, a novel synthetic method for N-(3, 5-dichlorophenyl)pyrido [2, 3-d]pyrimidin-4-amine was reported, which began from 2-aminonicotinonitrile, following condensation, cyclization and then Dimroth rearrangement reaction under microwave irradiation conditions. The over yield was 90%. Employing the same synthetic method, 20 pyrido [2, 3-d]pyrimidin- 4-amine derivatives were synthesized. We also compared microwave irradiation and oil bath heating for synthetizing the target products. The results showed that the method under microwave irradiation for the preparation of pyrido [2, 3-d]pyrimidin- 4-amine was time-saving and high yield. It is expected to become an efficient, gentle and environmentally friendly synthetic method of pyrido [2, 3-d]pyrimidin-4-amine.
In this paper, a novel synthetic method for N-(3, 5-dichlorophenyl)pyrido [2, 3-d]pyrimidin-4-amine was reported, which began from 2-aminonicotinonitrile, following condensation, cyclization and then Dimroth rearrangement reaction under microwave irradiation conditions. The over yield was 90%. Employing the same synthetic method, 20 pyrido [2, 3-d]pyrimidin- 4-amine derivatives were synthesized. We also compared microwave irradiation and oil bath heating for synthetizing the target products. The results showed that the method under microwave irradiation for the preparation of pyrido [2, 3-d]pyrimidin- 4-amine was time-saving and high yield. It is expected to become an efficient, gentle and environmentally friendly synthetic method of pyrido [2, 3-d]pyrimidin-4-amine.
2018, 38(5): 1172-1176
doi: 10.6023/cjoc201711050
Abstract:
Iodoalkynes and diiodoalkenes are valuable intermediates used extensively for C—C, C—O and C—N bonds formation. Therefore, the development of new method for the synthesis of these compunds is desirable. In this work, a novel and switchable protocol for the synthesis of iodoalkynes and diiodoalkenes has been developed, which were formed from terminal alkynes using the same reagent system of ZnI2 and tert-butyl nitrite in the presence or absence of triethylamine, respectively. The iodoalkyne formation is operationally simple, mild (weak base and room temperature), and tolerant of a large range of functional groups. In contrast, the diiodoalkene transformation shows interesting dependence on the electron property, and only electron-rich and neutral compounds are viable substrates. The control experiments performed suggest that iodoalkynes and diiodoalkenes are not interchangeable under a series of reaction conditions, including the optimized conditions, which can be explained by the mechanism in which both of the reactions involve a iodonium intermediate formed directly from a terminal alkyne.
Iodoalkynes and diiodoalkenes are valuable intermediates used extensively for C—C, C—O and C—N bonds formation. Therefore, the development of new method for the synthesis of these compunds is desirable. In this work, a novel and switchable protocol for the synthesis of iodoalkynes and diiodoalkenes has been developed, which were formed from terminal alkynes using the same reagent system of ZnI2 and tert-butyl nitrite in the presence or absence of triethylamine, respectively. The iodoalkyne formation is operationally simple, mild (weak base and room temperature), and tolerant of a large range of functional groups. In contrast, the diiodoalkene transformation shows interesting dependence on the electron property, and only electron-rich and neutral compounds are viable substrates. The control experiments performed suggest that iodoalkynes and diiodoalkenes are not interchangeable under a series of reaction conditions, including the optimized conditions, which can be explained by the mechanism in which both of the reactions involve a iodonium intermediate formed directly from a terminal alkyne.
2018, 38(5): 1185-1192
doi: 10.6023/cjoc201710019
Abstract:
Chiral tertiary alcohols (TAs) are key building blocks for the synthesis of many crucial flavor compounds and pharmaceuticals. The two enantiomers of tertiary alcohol, linalool, differ in odor. So, sustainable strategies for the manufacture of optically pure TAs represented by linalool, are highly desirable. But the enzymatic synthesis of chiral tertiary alcohols through kinetic resolution was not easily achieved, possibly because of the steric hindrance from the chemical structures of tertiary alcohols. Herein, we identified and functionally characterized a new microbial esterase EST112-2 from the antarctic sediments and utilized esterase EST112-2 as a green biocatalyst in the synthesis of chiral tertiary alcohol (S)-linalool through asymmetric hydrolysis of racemic linalyl acetate. Parameters such as pH, temperature, co-solvents, substrate concentrations, enzyme loading and reaction time were optimized for the kinetic resolutions. Desired chiral product (S)-linalool was finally obtained with an enantiomeric excess of over 66% and a yield of over 72% after process optimization. The enantiomeric excess of (S)-linalool prepared by esterase EST112-2 was much higher than that from previous reports.
Chiral tertiary alcohols (TAs) are key building blocks for the synthesis of many crucial flavor compounds and pharmaceuticals. The two enantiomers of tertiary alcohol, linalool, differ in odor. So, sustainable strategies for the manufacture of optically pure TAs represented by linalool, are highly desirable. But the enzymatic synthesis of chiral tertiary alcohols through kinetic resolution was not easily achieved, possibly because of the steric hindrance from the chemical structures of tertiary alcohols. Herein, we identified and functionally characterized a new microbial esterase EST112-2 from the antarctic sediments and utilized esterase EST112-2 as a green biocatalyst in the synthesis of chiral tertiary alcohol (S)-linalool through asymmetric hydrolysis of racemic linalyl acetate. Parameters such as pH, temperature, co-solvents, substrate concentrations, enzyme loading and reaction time were optimized for the kinetic resolutions. Desired chiral product (S)-linalool was finally obtained with an enantiomeric excess of over 66% and a yield of over 72% after process optimization. The enantiomeric excess of (S)-linalool prepared by esterase EST112-2 was much higher than that from previous reports.
2018, 38(5): 1261-1266
doi: 10.6023/cjoc201803001
Abstract:
An efficient synthesis of α-substituted 1, 2-dihydroquinoline compounds through the oxidative C—H functionalization of N-acyl-dihydroquinoline with diverse organoboron reagents mediated by triphenylcarbium perchlorate (Ph3CClO4) is reported. The reaction exhibits good functional group tolerance, allowing for C—H alkynylation and alkenylation proceeding smoothly in good yields.
An efficient synthesis of α-substituted 1, 2-dihydroquinoline compounds through the oxidative C—H functionalization of N-acyl-dihydroquinoline with diverse organoboron reagents mediated by triphenylcarbium perchlorate (Ph3CClO4) is reported. The reaction exhibits good functional group tolerance, allowing for C—H alkynylation and alkenylation proceeding smoothly in good yields.
2018, 38(5): 1267-1270
doi: 10.6023/cjoc201710033
Abstract:
Sifuvirtide (SFT) is a potent anti-HIV-1 (human immunodeficiency virus-1) fusion inhibitor and it shows higher potency and pharmacokinetic stability than the approved fusion inhibitor T20. At present, sifuvirtide has completed the phase Ⅱb clinical trial in China. In this study, SFT-1 and SFT-2 were synthesized via all-hydrocarbon cross-linking system with replacing the original salt bridge in SFT by hydrocarbon covalent bond, using sifuvirtide as template. The anti-HIV-1 activity was evaluated for all synthetic peptides. The results indicated that SFT stapled peptides displayed high inhibitory activity against seven HIV-1 pseudovirus strains, and SFT-1 showed the highest inhibitory activity against B' and B'C subtype virus strains, SFT-2 showed the highest inhibitory activity against B, CRF01_AE and CRF08_BC subtype virus strains.
Sifuvirtide (SFT) is a potent anti-HIV-1 (human immunodeficiency virus-1) fusion inhibitor and it shows higher potency and pharmacokinetic stability than the approved fusion inhibitor T20. At present, sifuvirtide has completed the phase Ⅱb clinical trial in China. In this study, SFT-1 and SFT-2 were synthesized via all-hydrocarbon cross-linking system with replacing the original salt bridge in SFT by hydrocarbon covalent bond, using sifuvirtide as template. The anti-HIV-1 activity was evaluated for all synthetic peptides. The results indicated that SFT stapled peptides displayed high inhibitory activity against seven HIV-1 pseudovirus strains, and SFT-1 showed the highest inhibitory activity against B' and B'C subtype virus strains, SFT-2 showed the highest inhibitory activity against B, CRF01_AE and CRF08_BC subtype virus strains.
