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2017 Volume 37 Issue 4
2017, 37(4): 777-797
doi: 10.6023/cjoc201610035
Abstract:
Nitric oxide as a biological messenger or effector molecule plays an important physiological role in the body. Owing to its various biological activities, it has received wide attention in clinical practice. Insufficient NO production in vivo is closely related with a variety of diseases. NO donor compounds can release NO in vivo to treat and prevent many diseases. With its wide application in medicine, the methods for the synthesis of NO donor compounds have attracted much attention of researchers. In this paper, the recent advances in the past 10 years in synthetic methods for NO donor compounds are reviewed.
Nitric oxide as a biological messenger or effector molecule plays an important physiological role in the body. Owing to its various biological activities, it has received wide attention in clinical practice. Insufficient NO production in vivo is closely related with a variety of diseases. NO donor compounds can release NO in vivo to treat and prevent many diseases. With its wide application in medicine, the methods for the synthesis of NO donor compounds have attracted much attention of researchers. In this paper, the recent advances in the past 10 years in synthetic methods for NO donor compounds are reviewed.
2017, 37(4): 798-809
doi: 10.6023/cjoc201611041
Abstract:
The vicinal dihalogens structure motif can be found in a variety of natural products and pharmaceuticals. The dihalogenation of alkenes is a commonly employed strategy for the rapid construction of carbon-halogen bonds in organic synthesis. In recent years, main progress has been achieved in the dihalogenation of alkenes. Based on our work and research interests, the aim of this review is to give an overview of the progress on the diverse synthetic methodologies of the dihalogenation of alkenes since 2000. Additionally, research trends of this area are also discussed.
The vicinal dihalogens structure motif can be found in a variety of natural products and pharmaceuticals. The dihalogenation of alkenes is a commonly employed strategy for the rapid construction of carbon-halogen bonds in organic synthesis. In recent years, main progress has been achieved in the dihalogenation of alkenes. Based on our work and research interests, the aim of this review is to give an overview of the progress on the diverse synthetic methodologies of the dihalogenation of alkenes since 2000. Additionally, research trends of this area are also discussed.
2017, 37(4): 810-823
doi: 10.6023/cjoc201611032
Abstract:
In view of the relevance between chemical structures and biosynthetic pathways of compounds that belong to the same family of natural products, MacMillan et al. (2011) proposed a strategy for the rapid and efficient synthesis of natural product within a family from a common intermediate or a group of similar intermediates, which is termed as collective synthesis. In recent years, this strategy has been applied for the synthesis of multiple family of natural products. Lycopodium alkaloids are a class of structurally diverse alkaloids, and many of them exhibiting good biological activity. In this review, the progress in the collective synthesis of Lycopodium alkaloids is summarized.
In view of the relevance between chemical structures and biosynthetic pathways of compounds that belong to the same family of natural products, MacMillan et al. (2011) proposed a strategy for the rapid and efficient synthesis of natural product within a family from a common intermediate or a group of similar intermediates, which is termed as collective synthesis. In recent years, this strategy has been applied for the synthesis of multiple family of natural products. Lycopodium alkaloids are a class of structurally diverse alkaloids, and many of them exhibiting good biological activity. In this review, the progress in the collective synthesis of Lycopodium alkaloids is summarized.
2017, 37(4): 824-840
doi: 10.6023/cjoc201611017
Abstract:
3-Isothiocyanato oxindoles have been widely employed as a class of highly reactive and novel reagents in the enantioselective synthesis of diverse spirooxindoles. This review summarizes the recent advances of 3-isothiocyanato oxindoles mediated some types of cascade process in the past six years, including properties of reaction, activation models and synthetic applications. Furthermore, the prospects of this concept are also discussed.
3-Isothiocyanato oxindoles have been widely employed as a class of highly reactive and novel reagents in the enantioselective synthesis of diverse spirooxindoles. This review summarizes the recent advances of 3-isothiocyanato oxindoles mediated some types of cascade process in the past six years, including properties of reaction, activation models and synthetic applications. Furthermore, the prospects of this concept are also discussed.
2017, 37(4): 841-857
doi: 10.6023/cjoc201610010
Abstract:
Compounds containing aryl structures are important organic synthesis intermediates, which are widely present in a large family of natural products and bioactive molecules. In recent years, direct asymmetric functionalization of benzylic C (sp3)—H bond for the efficient construction of arene and hetero-arene motifs with high stereoselectivity has drawn widespread concern from chemical community. Among the various strategies, small molecule-catalyzed metal-free functionalization of benzylic C (sp3)—H bond represents a more challenging but promising transformations. This review is intended to summarize and discuss the most recent advances in this area.
Compounds containing aryl structures are important organic synthesis intermediates, which are widely present in a large family of natural products and bioactive molecules. In recent years, direct asymmetric functionalization of benzylic C (sp3)—H bond for the efficient construction of arene and hetero-arene motifs with high stereoselectivity has drawn widespread concern from chemical community. Among the various strategies, small molecule-catalyzed metal-free functionalization of benzylic C (sp3)—H bond represents a more challenging but promising transformations. This review is intended to summarize and discuss the most recent advances in this area.
2017, 37(4): 858-865
doi: 10.6023/cjoc201612041
Abstract:
G protein coupled receptor 40 (GPR40) is a potential target for treatment of type 2 diabetes. Herein, the well-known GPR40 agonist TAK-875 (compound 1) was synthesized as a positive control. Besides, an epimeric mixture 11, which was the sulfoxide analog of compound 1 was also synthesized. The following chiral HPLC separation of 11 led to optically pure compounds 12 (S, S, 100.0% de) and 13 (R, S, 100.0% de), of which the absolute configurations were determined by circular dichroism spectra analysis. In vitro biological activity evaluation results showed that the GPR40 agonistic potency of epimeric mixture 11 (EC50=77.5 nmol·L-1) and its two optically pure epimers (12, EC50=76.1 nmol·L-1; 13, EC50=114.0 nmol·L-1) were comparable to that of compound 1 (EC50=84.3 nmol·L-1), which was rationalized by docking analysis. Compounds 12 and 13 warrant further drug-like property evaluation due to their promising potency and novel structures.
G protein coupled receptor 40 (GPR40) is a potential target for treatment of type 2 diabetes. Herein, the well-known GPR40 agonist TAK-875 (compound 1) was synthesized as a positive control. Besides, an epimeric mixture 11, which was the sulfoxide analog of compound 1 was also synthesized. The following chiral HPLC separation of 11 led to optically pure compounds 12 (S, S, 100.0% de) and 13 (R, S, 100.0% de), of which the absolute configurations were determined by circular dichroism spectra analysis. In vitro biological activity evaluation results showed that the GPR40 agonistic potency of epimeric mixture 11 (EC50=77.5 nmol·L-1) and its two optically pure epimers (12, EC50=76.1 nmol·L-1; 13, EC50=114.0 nmol·L-1) were comparable to that of compound 1 (EC50=84.3 nmol·L-1), which was rationalized by docking analysis. Compounds 12 and 13 warrant further drug-like property evaluation due to their promising potency and novel structures.
2017, 37(4): 866-872
doi: 10.6023/cjoc201701006
Abstract:
A three-component reaction for the synthesis of poly-substituted pyridines from β-keto esters, chalcones and ammonium acetate promoted by iodine has been reported. Advantages of the present method include ready availability of starting materials, broad scope of substrates, and convenience of operation.
A three-component reaction for the synthesis of poly-substituted pyridines from β-keto esters, chalcones and ammonium acetate promoted by iodine has been reported. Advantages of the present method include ready availability of starting materials, broad scope of substrates, and convenience of operation.
2017, 37(4): 873-880
doi: 10.6023/cjoc201611026
Abstract:
Seven gardenamide A (GA)/tacrine hybrids have been designed and synthesized. Firstly, 10-gardenamide A (DG) aldehyde was prepared through 5 steps reactions applied genipin as starting material. The overyield was 20.4%. Then, N-terminated aminoalkyltacrine (TN-n) was synthesized via 4 steps reactions started from o-aminobenzoic acid. The overall yield was 50.0%~65.4%. After that, DG reacted with TN-n at the presence of appropriate reductant leading to the target compounds. The yields were from 37% to 54%. The structures of all the target compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The bioactivities of all the hybrids were evaluated by setting up 6-hydroxydopamine-induced impaired PC12 cell model. It was indicated that two hybrids TNG-1 and TNG-5 showed better neuroprotective activity than tacrine, GA or their combination. Based on this fact, it was proposed that the hybrids TNG-1 and TNG-5 were better drug-like candidates than both monomers.
Seven gardenamide A (GA)/tacrine hybrids have been designed and synthesized. Firstly, 10-gardenamide A (DG) aldehyde was prepared through 5 steps reactions applied genipin as starting material. The overyield was 20.4%. Then, N-terminated aminoalkyltacrine (TN-n) was synthesized via 4 steps reactions started from o-aminobenzoic acid. The overall yield was 50.0%~65.4%. After that, DG reacted with TN-n at the presence of appropriate reductant leading to the target compounds. The yields were from 37% to 54%. The structures of all the target compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The bioactivities of all the hybrids were evaluated by setting up 6-hydroxydopamine-induced impaired PC12 cell model. It was indicated that two hybrids TNG-1 and TNG-5 showed better neuroprotective activity than tacrine, GA or their combination. Based on this fact, it was proposed that the hybrids TNG-1 and TNG-5 were better drug-like candidates than both monomers.
2017, 37(4): 881-888
doi: 10.6023/cjoc201611003
Abstract:
A concise and efficient protocol for the synthesis of novel quinolinone derivatives 4 has been established from a intramolecular cyclization of cyanoacetylenaminones 3, which were synthesized by the regio-selective cyanoacylation reaction of β-enaminones 1 with cyanoacetic acid 2. The reaction was performed in acetonitrile media at 40 ℃, and piperidine as catalyst. As a result, a novel series of quinolinones 4a~4t were obtained with the yields of 82%~95%. The reaction is particularly attractive due to the following advantages of operational simplicity, atom economy, simple starting materials, and easy purification.
A concise and efficient protocol for the synthesis of novel quinolinone derivatives 4 has been established from a intramolecular cyclization of cyanoacetylenaminones 3, which were synthesized by the regio-selective cyanoacylation reaction of β-enaminones 1 with cyanoacetic acid 2. The reaction was performed in acetonitrile media at 40 ℃, and piperidine as catalyst. As a result, a novel series of quinolinones 4a~4t were obtained with the yields of 82%~95%. The reaction is particularly attractive due to the following advantages of operational simplicity, atom economy, simple starting materials, and easy purification.
2017, 37(4): 889-895
doi: 10.6023/cjoc201611008
Abstract:
A novel imidazophenazine lactam fluorescence chemosensor (S1) was designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS techniques. Fluorescence spectra of S1 in dimethyl sulfoxide (DMSO) solution were measured. Its maximum emission wavelength was 524 nm. The DMSO solution of S1 has bright yellow fluorescence. Respectively, to the S1 solution add F-, Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, and SCN-, the fluorescent color of the solution didn't change. Only the CN- addition, the fluorescent color of the S1 solution changed from yellow to orange-red, indicating that S1 has good specific selectivity for CN-. The results of anti-disturbance experiment demonstrated that S1 detect CN- without interference from other anions. By calculation, the linear of the fluorescence of the sensor for CN- is 9.96×10-7. This value is lower than the World Health Organization (WHO) provisions of the cyanide content of drinking water. Mechanism studies show that S1 is a fluorescence sensor by reactive recognition CN-. In addition, the application of sensor S1 supported on solid silica gel was used as a solid material to detecting solid NaCN and CN- in pure water.
A novel imidazophenazine lactam fluorescence chemosensor (S1) was designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS techniques. Fluorescence spectra of S1 in dimethyl sulfoxide (DMSO) solution were measured. Its maximum emission wavelength was 524 nm. The DMSO solution of S1 has bright yellow fluorescence. Respectively, to the S1 solution add F-, Cl-, Br-, I-, AcO-, H2PO4-, HSO4-, ClO4-, and SCN-, the fluorescent color of the solution didn't change. Only the CN- addition, the fluorescent color of the S1 solution changed from yellow to orange-red, indicating that S1 has good specific selectivity for CN-. The results of anti-disturbance experiment demonstrated that S1 detect CN- without interference from other anions. By calculation, the linear of the fluorescence of the sensor for CN- is 9.96×10-7. This value is lower than the World Health Organization (WHO) provisions of the cyanide content of drinking water. Mechanism studies show that S1 is a fluorescence sensor by reactive recognition CN-. In addition, the application of sensor S1 supported on solid silica gel was used as a solid material to detecting solid NaCN and CN- in pure water.
2017, 37(4): 896-901
doi: 10.6023/cjoc201611014
Abstract:
A new fluorescence probe L based on carbazole Schiff-base for Cu2+ was synthesized. The recognition ability of probe L to metal ions was investigated by UV-Vis and fluorescence spectra. The experimental results showed that the probe L in CH3CN displayed a distinct color change from yellow to colorless upon the addition of Cu2+, which can be directly detected by the naked eye for Cu2+. The fluorescence spectra showed that the probe L had high selective and sensitive recognition toward Cu2+ in CH3CN, the fluorescence intensity was increased with the increase of Cu2+ concentration, and it was not affected by other metal ions. The association constant between the probe L and Cu2+ was detected to be 1.38×104 L/mol and the corresponding detection limit was calculated to be 2.34×10-7 mol/L. The detection limit of L for Cu2+ was far lower than the maximum allowable level of the WHO limit (20 mmol/L) for drinking water. The results indicate that the probe L should be applicable to the research on the environmental applications associated with Cu2+.
A new fluorescence probe L based on carbazole Schiff-base for Cu2+ was synthesized. The recognition ability of probe L to metal ions was investigated by UV-Vis and fluorescence spectra. The experimental results showed that the probe L in CH3CN displayed a distinct color change from yellow to colorless upon the addition of Cu2+, which can be directly detected by the naked eye for Cu2+. The fluorescence spectra showed that the probe L had high selective and sensitive recognition toward Cu2+ in CH3CN, the fluorescence intensity was increased with the increase of Cu2+ concentration, and it was not affected by other metal ions. The association constant between the probe L and Cu2+ was detected to be 1.38×104 L/mol and the corresponding detection limit was calculated to be 2.34×10-7 mol/L. The detection limit of L for Cu2+ was far lower than the maximum allowable level of the WHO limit (20 mmol/L) for drinking water. The results indicate that the probe L should be applicable to the research on the environmental applications associated with Cu2+.
2017, 37(4): 902-907
doi: 10.6023/cjoc201612007
Abstract:
In order to investigate whether the modification at the double bonds in the pyrone skeleton would affect their biological activity. Based on the 5, 6-dihydro-6-alkyl-2-pyrone goniothalamin, a series of new compounds 5, 6 and 8 were designed and synthesized, which were obtained by modification at the unsubstituted double bonds. Their cell proliferation inhibition activities against human liver cancer (7721), human lung cancer (A549), human esophageal cancer (EC-109), human gastric cancer (MGC-803) cell lines were assessed by thiazolyl blue tetrazolium bromide (MTT) method. Most of synthetic compounds lost their bioactivities via a comparision with positive control but 6-(benzyloxy) methyl-3-methyl-4-(2, 3, 4, 5-tetra-fluorobenzamine)-5, 6-dihydro-2H-pyran-2-one (6d). The results indicate that the unsaturated double bond is a key functional group for the bioactivity of these compounds and it is possible to keep their anti-cancer proliferation activity and reduce their toxicity by modification of the unsaturated double bond in 5, 6-dihydro-6-alkyl-2-pyrones.
In order to investigate whether the modification at the double bonds in the pyrone skeleton would affect their biological activity. Based on the 5, 6-dihydro-6-alkyl-2-pyrone goniothalamin, a series of new compounds 5, 6 and 8 were designed and synthesized, which were obtained by modification at the unsubstituted double bonds. Their cell proliferation inhibition activities against human liver cancer (7721), human lung cancer (A549), human esophageal cancer (EC-109), human gastric cancer (MGC-803) cell lines were assessed by thiazolyl blue tetrazolium bromide (MTT) method. Most of synthetic compounds lost their bioactivities via a comparision with positive control but 6-(benzyloxy) methyl-3-methyl-4-(2, 3, 4, 5-tetra-fluorobenzamine)-5, 6-dihydro-2H-pyran-2-one (6d). The results indicate that the unsaturated double bond is a key functional group for the bioactivity of these compounds and it is possible to keep their anti-cancer proliferation activity and reduce their toxicity by modification of the unsaturated double bond in 5, 6-dihydro-6-alkyl-2-pyrones.
2017, 37(4): 908-913
doi: 10.6023/cjoc201610027
Abstract:
In order to find efficient, low toxicity, eco-friendly insecticides, novel chiral carbon and sulfur phthalic acid diamide derivatives containing pyridine substitute were designed and synthesized for further studying the structure-activity relationship of dual-chiral sulfilimines and sulfoximines. Their structures were confirmed by NMR and HRMS. The preliminary results of biological evaluation showed that the most compounds exhibited moderate larvicidal activity. These results provide a theoretical basis for the study of the dicarboxamide structures containing sulfiliminyl and sulfoximinyl moieties.
In order to find efficient, low toxicity, eco-friendly insecticides, novel chiral carbon and sulfur phthalic acid diamide derivatives containing pyridine substitute were designed and synthesized for further studying the structure-activity relationship of dual-chiral sulfilimines and sulfoximines. Their structures were confirmed by NMR and HRMS. The preliminary results of biological evaluation showed that the most compounds exhibited moderate larvicidal activity. These results provide a theoretical basis for the study of the dicarboxamide structures containing sulfiliminyl and sulfoximinyl moieties.
2017, 37(4): 914-919
doi: 10.6023/cjoc201610029
Abstract:
The Strecker reaction of ethyl cyanoformate with aldimines was carried out with N-heterocyclic carbene (NHC) as the catalyst. The reaction conditions were optimized with different catalysts, catalyst loading and various solvents. 14 α-aminonitriles were synthesized via the optimal reaction conditions. It was found that both aromatic and aliphatic aldimines were suitable electrophiles and the highest yield was 93%. The reaction has the virtue of simple operation, mild reaction condition, high yield and environment friendliness.
The Strecker reaction of ethyl cyanoformate with aldimines was carried out with N-heterocyclic carbene (NHC) as the catalyst. The reaction conditions were optimized with different catalysts, catalyst loading and various solvents. 14 α-aminonitriles were synthesized via the optimal reaction conditions. It was found that both aromatic and aliphatic aldimines were suitable electrophiles and the highest yield was 93%. The reaction has the virtue of simple operation, mild reaction condition, high yield and environment friendliness.
2017, 37(4): 920-924
doi: 10.6023/cjoc201610046
Abstract:
In the presence of FeCl3 reaction of alkenols with iodine resulted in intramolecular addition of hydroxyl to alkenol to produce a wide range of iodocyclic ethers in good to excellent yields under mild reaction conditions. The advantages of our procedure include a decreased amount of iodine as well as short reaction times. The broad scope, mild reaction conditions, and experimental ease of this transformation have made it a valuable alternative to current available methods for the preparation of iodocyclic ethers.
In the presence of FeCl3 reaction of alkenols with iodine resulted in intramolecular addition of hydroxyl to alkenol to produce a wide range of iodocyclic ethers in good to excellent yields under mild reaction conditions. The advantages of our procedure include a decreased amount of iodine as well as short reaction times. The broad scope, mild reaction conditions, and experimental ease of this transformation have made it a valuable alternative to current available methods for the preparation of iodocyclic ethers.
2017, 37(4): 925-935
doi: 10.6023/cjoc201611009
Abstract:
An one-pot reaction of trifluoroacetaldehyde methyl hemiacetal or trifluoroketones, acylhydrazines and allyl bromide promoted by indium powder is reported, and a series of trifluoromethylated homoallylic N-acylhydrazines were obtained with good to excellent yields. The features of this process include readily available starting materials as trifluoromethyl building blocks, mild conditions and easy operation.
An one-pot reaction of trifluoroacetaldehyde methyl hemiacetal or trifluoroketones, acylhydrazines and allyl bromide promoted by indium powder is reported, and a series of trifluoromethylated homoallylic N-acylhydrazines were obtained with good to excellent yields. The features of this process include readily available starting materials as trifluoromethyl building blocks, mild conditions and easy operation.
2017, 37(4): 936-942
doi: 10.6023/cjoc201612006
Abstract:
An asymmetric Henry reaction with 2, 2, 2-trifluoroacetophenone as trifluoromethyl building block was described. This reaction was catalyzed by bifunctional thiourea derived from quinine to give the product bearing a CF3 stereogenic center in good yield with good enantioselectivity.
An asymmetric Henry reaction with 2, 2, 2-trifluoroacetophenone as trifluoromethyl building block was described. This reaction was catalyzed by bifunctional thiourea derived from quinine to give the product bearing a CF3 stereogenic center in good yield with good enantioselectivity.
2017, 37(4): 943-953
doi: 10.6023/cjoc201610044
Abstract:
33 novel 4-substituted thienyl pyrrole compounds were synthesized via replacement, Vilsmeier-Hack, aldol condensation and Van Leusen pyrrole reaction using 2-methoxythiophen, 3-methoxythiophene, 3, 4-dibromothiophene and substituted acetophenone as raw materials. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS, meanwhile the cell proliferation inhibition efficacy was estimated against CHO, HCT-116, MGC80-3, SGC-7901 and HUVEC cell lines. The results revealed that some target compounds exhibited strong (IC50 ≤ 20 μmol/L) or moderate (20 μmol/L < IC50 ≤ 50 μmol/L) proliferation inhibition efficacy against tumor cells, meanwhile no significant inhibition activity on HUVEC, which indicated that these compounds had high selectivity. Herein, some compounds showed strong or moderate inhibition efficacy against MGC80-3. The IC50 values of [4-(3, 4-dimethoxythiophen-2-yl)-1H-pyrrol-3-yl](4-phenylphenyl)-methanone (4a-2) and [4-(3, 4-dimethoxythiophen-2-yl)-1H-pyrrol-3-yl](3-bromophenyl) methanone (4a-7), were 8.6 and 8.5 μmol/L against MGC80-3, respectively, and the IC50 value of 4a-7 was 20.0 μmol/L against HCT-116. Both compounds 4a-2 and 4a-7 exhibited moderate inhibition efficacy against SGC-7901.
33 novel 4-substituted thienyl pyrrole compounds were synthesized via replacement, Vilsmeier-Hack, aldol condensation and Van Leusen pyrrole reaction using 2-methoxythiophen, 3-methoxythiophene, 3, 4-dibromothiophene and substituted acetophenone as raw materials. The structures of all target compounds were characterized by 1H NMR, 13C NMR and HRMS, meanwhile the cell proliferation inhibition efficacy was estimated against CHO, HCT-116, MGC80-3, SGC-7901 and HUVEC cell lines. The results revealed that some target compounds exhibited strong (IC50 ≤ 20 μmol/L) or moderate (20 μmol/L < IC50 ≤ 50 μmol/L) proliferation inhibition efficacy against tumor cells, meanwhile no significant inhibition activity on HUVEC, which indicated that these compounds had high selectivity. Herein, some compounds showed strong or moderate inhibition efficacy against MGC80-3. The IC50 values of [4-(3, 4-dimethoxythiophen-2-yl)-1H-pyrrol-3-yl](4-phenylphenyl)-methanone (4a-2) and [4-(3, 4-dimethoxythiophen-2-yl)-1H-pyrrol-3-yl](3-bromophenyl) methanone (4a-7), were 8.6 and 8.5 μmol/L against MGC80-3, respectively, and the IC50 value of 4a-7 was 20.0 μmol/L against HCT-116. Both compounds 4a-2 and 4a-7 exhibited moderate inhibition efficacy against SGC-7901.
2017, 37(4): 954-958
doi: 10.6023/cjoc201611020
Abstract:
Benzodiazepinones are the important class of organic heterocyclic compounds with physiological activities. Herein, one pot procedure for the synthesis of benzodiazepinones has been developed under solvent-free condition. The substituted ethyl 2-bromobenzoates were cross-coupled with adjacent diamine compounds using CuI as a catalyst to give the intermediates, which spontaneously underwent an intramolecular N-acylation producing corresponding benzodiazepinones. This method has the advantages of enviroment frendly, mild reaction conditions, simple one pot operation and high yields. Under the optimized conditions, the effect of various substituted group on the reaction was investigated and the tolerance of this system was evaluated. This protocol could tolerate a variety of functional groups, and provide efficient access to a wide variety of substituted benzodiazepinones in good yields, including biological active molecules.
Benzodiazepinones are the important class of organic heterocyclic compounds with physiological activities. Herein, one pot procedure for the synthesis of benzodiazepinones has been developed under solvent-free condition. The substituted ethyl 2-bromobenzoates were cross-coupled with adjacent diamine compounds using CuI as a catalyst to give the intermediates, which spontaneously underwent an intramolecular N-acylation producing corresponding benzodiazepinones. This method has the advantages of enviroment frendly, mild reaction conditions, simple one pot operation and high yields. Under the optimized conditions, the effect of various substituted group on the reaction was investigated and the tolerance of this system was evaluated. This protocol could tolerate a variety of functional groups, and provide efficient access to a wide variety of substituted benzodiazepinones in good yields, including biological active molecules.
2017, 37(4): 959-966
doi: 10.6023/cjoc201610016
Abstract:
A series of pyridine chalcone derivatives were designed and synthesized. The structures were confirmed by 1H NMR, 13C NMR and HRMS. In vitro biological activity evaluation results showed that five of the compounds exhibited good biological activity against gram positive bacteria staphylococcus aureus (ATCC 29213). Further antibiotic activity of these five compounds against 11 clinical isolated methicillin-resistant staphylococcus aureus (MRSA) were evaluated. The results showed that four of the compounds exhibited good antibacterial activity against MRSA. (E)-2-Bromo-N-{4-[3-(pyridin-2-yl)-acryloyl]phenyl}acetamide (5k) showed the most effective activity (minimum inhibitory concentration, MIC=4 μg/mL). In terms of hemolytic activity evaluation, compound 5k showed virtually no toxicity even in 1000 μg/mL concentration. To sum up, pyridine chalcone 5k was potential for further antibiotic study as anti-MRSA agent.
A series of pyridine chalcone derivatives were designed and synthesized. The structures were confirmed by 1H NMR, 13C NMR and HRMS. In vitro biological activity evaluation results showed that five of the compounds exhibited good biological activity against gram positive bacteria staphylococcus aureus (ATCC 29213). Further antibiotic activity of these five compounds against 11 clinical isolated methicillin-resistant staphylococcus aureus (MRSA) were evaluated. The results showed that four of the compounds exhibited good antibacterial activity against MRSA. (E)-2-Bromo-N-{4-[3-(pyridin-2-yl)-acryloyl]phenyl}acetamide (5k) showed the most effective activity (minimum inhibitory concentration, MIC=4 μg/mL). In terms of hemolytic activity evaluation, compound 5k showed virtually no toxicity even in 1000 μg/mL concentration. To sum up, pyridine chalcone 5k was potential for further antibiotic study as anti-MRSA agent.
2017, 37(4): 967-974
doi: 10.6023/cjoc201611006
Abstract:
Based on our previous work, twenty-three novel 2, 4-diaminopyrimidine derivatives bearing indole moiety were designed and synthesized. Structures of all compounds were elucidated by 1H NMR, 13C NMR and HRMS. Antiproliferative activities for all these compounds were evaluated by the method of methyl thiazolyl tetrazolium (MTT) assay against four cancer cell lines (HeLa, MD-MBA-231, PC-3 and HCT116), and the results demonstrated that some compounds possessed significant antitumor activities in vitro. Particularly, the most promising ethyl (2-((2-benzoyl-5-chloro-1H-indol-3-yl) amino)-5-nitropyrimidin-4-yl) glycinate (8j) displayed 2.0-and 0.5-fold improvement compared to fluorouracil in inhibiting HCT116, and MD-MBA-231 cell proliferation with IC50 values of 23.15 and 36.88 mmol/L, respectively. These findings suggest that compound 8j may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
Based on our previous work, twenty-three novel 2, 4-diaminopyrimidine derivatives bearing indole moiety were designed and synthesized. Structures of all compounds were elucidated by 1H NMR, 13C NMR and HRMS. Antiproliferative activities for all these compounds were evaluated by the method of methyl thiazolyl tetrazolium (MTT) assay against four cancer cell lines (HeLa, MD-MBA-231, PC-3 and HCT116), and the results demonstrated that some compounds possessed significant antitumor activities in vitro. Particularly, the most promising ethyl (2-((2-benzoyl-5-chloro-1H-indol-3-yl) amino)-5-nitropyrimidin-4-yl) glycinate (8j) displayed 2.0-and 0.5-fold improvement compared to fluorouracil in inhibiting HCT116, and MD-MBA-231 cell proliferation with IC50 values of 23.15 and 36.88 mmol/L, respectively. These findings suggest that compound 8j may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
2017, 37(4): 975-986
doi: 10.6023/cjoc201611013
Abstract:
The regioselective addition-elimination of 3-acetyl-4-methoxy-2-butenolide and 3-(1-methoxy ethylidene) furan-2, 4-dione having enol ether with different amines yielded novel stable enaminone derivatives in ethanol solution. Their structures were elucidated by 1H NMR, 13C NMR, HRMS and X-ray diffraction data. Among of them, the Z/E isomers were observed for 3-(1-aminoethylidene)-furan-2, 4-dione. The structures of byproducts for preparing intermediates and title compounds were also characterized.
The regioselective addition-elimination of 3-acetyl-4-methoxy-2-butenolide and 3-(1-methoxy ethylidene) furan-2, 4-dione having enol ether with different amines yielded novel stable enaminone derivatives in ethanol solution. Their structures were elucidated by 1H NMR, 13C NMR, HRMS and X-ray diffraction data. Among of them, the Z/E isomers were observed for 3-(1-aminoethylidene)-furan-2, 4-dione. The structures of byproducts for preparing intermediates and title compounds were also characterized.
2017, 37(4): 987-995
doi: 10.6023/cjoc201611028
Abstract:
In order to discover novel compounds with high-activity to control aphid, aphid alarm pheromone (E)-β-farnesene (EBF) was chosen as lead compound and a series of EBF analogues containing imidogen were designed by replacing unstable conjugated double bonds of EBF with different aromatic ring. Nineteen EBF analogues were synthesized via two reaction routes of N-alkylation and reductive amination. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis. The bioassay and structure-activity relationship analysis were carried out. The result indicated that title compounds containing benzene or pyridine displayed obvious repellent activity against Myzus persicae (Sulzer). Especially, compounds 3g, 3l and 3m exhibited excellent repellent activity of 62.0%, 62.5% and 64.6% respectively. Moreover, the title compounds containing 1, 3, 4-thiadiazole ring showed certain insecticidal activity against M. persicae. In particular, the mortality rate of compounds 3i, 3l, 3r and 3s were 70.7%, 72.6%, 70.4% and 75.5% at a concentration of 200 μg/mL, which were higher than the lead EBF. However, compound 3a, in which the conjugated double bonds were replaced with butyl, showed obviously neither repellent nor aphicidal activity.
In order to discover novel compounds with high-activity to control aphid, aphid alarm pheromone (E)-β-farnesene (EBF) was chosen as lead compound and a series of EBF analogues containing imidogen were designed by replacing unstable conjugated double bonds of EBF with different aromatic ring. Nineteen EBF analogues were synthesized via two reaction routes of N-alkylation and reductive amination. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis. The bioassay and structure-activity relationship analysis were carried out. The result indicated that title compounds containing benzene or pyridine displayed obvious repellent activity against Myzus persicae (Sulzer). Especially, compounds 3g, 3l and 3m exhibited excellent repellent activity of 62.0%, 62.5% and 64.6% respectively. Moreover, the title compounds containing 1, 3, 4-thiadiazole ring showed certain insecticidal activity against M. persicae. In particular, the mortality rate of compounds 3i, 3l, 3r and 3s were 70.7%, 72.6%, 70.4% and 75.5% at a concentration of 200 μg/mL, which were higher than the lead EBF. However, compound 3a, in which the conjugated double bonds were replaced with butyl, showed obviously neither repellent nor aphicidal activity.
2017, 37(4): 996-999
doi: 10.6023/cjoc201702027
Abstract:
Two new rhabduscin analogues were isolated and purified from fermentation broth of Xenorhabdus bovienii SN52 by silica gel column chromatography, sephadex LH-20 chromatography and high performance preparative liquid chromatography. On the basis of spectroscopic methods (HR-ESIMS, 1D-and 2D-NMR) and by comparison with those reported previously, their structures were identified as 4-O-(4-acetamide-β-L-rhamnoside)-benzaldehyde (1) and 4-O-(4-acetamide-β-L-rhamnoside)-(Z)-N-styrylforma mide (2). Their inhibitory activities against phenoloxidase were also tested.
Two new rhabduscin analogues were isolated and purified from fermentation broth of Xenorhabdus bovienii SN52 by silica gel column chromatography, sephadex LH-20 chromatography and high performance preparative liquid chromatography. On the basis of spectroscopic methods (HR-ESIMS, 1D-and 2D-NMR) and by comparison with those reported previously, their structures were identified as 4-O-(4-acetamide-β-L-rhamnoside)-benzaldehyde (1) and 4-O-(4-acetamide-β-L-rhamnoside)-(Z)-N-styrylforma mide (2). Their inhibitory activities against phenoloxidase were also tested.
2017, 37(4): 1000-1008
doi: 10.6023/cjoc201611039
Abstract:
Sixteen novel dithiocarbamates containing 1, 2, 3-trizaole and [1-bi (4-fluorophenyl) methyl]piperazine group were prepared via two steps starting from [1-bi (4-fluorophenyl) methyl]piperazine, propargyl bromide, methanedithione and sodium azide, using a very simple catalytic system composed of 5 mol% copper (Ⅰ) iodide and DMF-H2O (V:V=1:1) as solvent at 70 ℃ for 4 h with moderate yield (34%~65%). The structures of the new compounds were characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. The bioactive assay for the newly prepared compounds manifested that fourteen dithiocarbamate derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 μg/mL (inhibitiory rate up to 97.96%, IC50 value up to 11.55 μg/mL), and six dithiocarbamate derivatives exhibited excellent inhibitory activity against leukemia HL-60 and lung cancer A-549 cell in 40 μmol·L-1 (inhibitiory rate up to 99.99% and 93.91%, respectively; IC50 value up to 12.11 and 22.45 μg/mL, respectively).
Sixteen novel dithiocarbamates containing 1, 2, 3-trizaole and [1-bi (4-fluorophenyl) methyl]piperazine group were prepared via two steps starting from [1-bi (4-fluorophenyl) methyl]piperazine, propargyl bromide, methanedithione and sodium azide, using a very simple catalytic system composed of 5 mol% copper (Ⅰ) iodide and DMF-H2O (V:V=1:1) as solvent at 70 ℃ for 4 h with moderate yield (34%~65%). The structures of the new compounds were characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. The bioactive assay for the newly prepared compounds manifested that fourteen dithiocarbamate derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 μg/mL (inhibitiory rate up to 97.96%, IC50 value up to 11.55 μg/mL), and six dithiocarbamate derivatives exhibited excellent inhibitory activity against leukemia HL-60 and lung cancer A-549 cell in 40 μmol·L-1 (inhibitiory rate up to 99.99% and 93.91%, respectively; IC50 value up to 12.11 and 22.45 μg/mL, respectively).
2017, 37(4): 1009-1015
doi: 10.6023/cjoc201610026
Abstract:
In order to find novel biologically active heterocyclic compounds, fifteen novel 1, 3, 4-thiadiazole thioether derivatives carrying pyrimidine moiety were prepared by using thiocarbamide and 2, 4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and the last benzylation reaction under microwave irradiation. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR, IR, ESI-MS and elemental analysis. The preliminary bioassay results indicated that some target compounds exhibited moderate inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((3-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7i) against Colletrotichum acutatum and Colletrotichum fragariae were 79.84% and 73.46% respectively. Several compounds also showed good antileishmanial activities against Leishmania donovani, 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((2-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7h) and 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((4-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7j) were found highly active with IC50 values of 21.3 and 23.6 μg/mL, respectively.
In order to find novel biologically active heterocyclic compounds, fifteen novel 1, 3, 4-thiadiazole thioether derivatives carrying pyrimidine moiety were prepared by using thiocarbamide and 2, 4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and the last benzylation reaction under microwave irradiation. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR, IR, ESI-MS and elemental analysis. The preliminary bioassay results indicated that some target compounds exhibited moderate inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((3-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7i) against Colletrotichum acutatum and Colletrotichum fragariae were 79.84% and 73.46% respectively. Several compounds also showed good antileishmanial activities against Leishmania donovani, 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((2-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7h) and 2-(((4, 6-dimethylpyrimidin-2-yl) thio) methyl)-5-((4-fluorobenzyl) thio)-1, 3, 4-thiadiazole (7j) were found highly active with IC50 values of 21.3 and 23.6 μg/mL, respectively.
2017, 37(4): 1016-1019
doi: 10.6023/cjoc201611021
Abstract:
Investigation on Kalimeris integrifolia resulted in two compounds by means of various chromatographic techniques (silica gel, Sephadex LH-20, RP-LC and Pre-HPLC). Their structures were determined as 5, 8-dihydroxy-2-(3-hydroxy-4, 5-dimethoxyphenyl)-6, 7-dimethoxy-4H-chromen-4-one (1) and 5-hydroxy-6, 7-dimethoxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-8-yl 2-methylbutanoate (2) on the basis of extensive spectroscopic analyses including MS, IR, UV, 1D-and 2D-NMR. Among them, compounds 1 and 2 are two new flavonoids, named as kalinturflavone A (1) and kalinturflavone B (2).
Investigation on Kalimeris integrifolia resulted in two compounds by means of various chromatographic techniques (silica gel, Sephadex LH-20, RP-LC and Pre-HPLC). Their structures were determined as 5, 8-dihydroxy-2-(3-hydroxy-4, 5-dimethoxyphenyl)-6, 7-dimethoxy-4H-chromen-4-one (1) and 5-hydroxy-6, 7-dimethoxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-8-yl 2-methylbutanoate (2) on the basis of extensive spectroscopic analyses including MS, IR, UV, 1D-and 2D-NMR. Among them, compounds 1 and 2 are two new flavonoids, named as kalinturflavone A (1) and kalinturflavone B (2).
Synthesis and Biological Activities of Novel Pyrazole Oximes Containing Substituted Pyrimidine Group
2017, 37(4): 1020-1026
doi: 10.6023/cjoc201611042
Abstract:
In order to explore novel potent pesticide from pyrazole oxime derivatives, a series of new pyrazole oxime compounds carrying substituted pyrimidine moiety were synthesized by the method of active substructure combination. The structures of the title compounds were characterized by 1H NMR, 13C NMR, MS and elemental analysis. Preliminary bioassay data displayed that some target compounds showed certain insecticidal activities. At the concentration of 500 μg/mL, compounds 6b and 6c exhibited 60% and 70% insecticidal activity against Aphis craccivora, compounds 6a, 6b, 6c, and 6d had 100%, 100%, 100% and 90% insecticidal activity against Nilaparvata lugens. When the concentration was reduced to 100 μg/mL, compounds 6a, 6b and 6d were still active against Nilaparvata lugens with inhibitory values of 60%, 60% and 50%, respectively. In addition, insecticidal activities against Oriental armyworm of compounds 6f, 6g and 6m were 80%, 70% and 90%, respectively, at 500 μg/mL.
In order to explore novel potent pesticide from pyrazole oxime derivatives, a series of new pyrazole oxime compounds carrying substituted pyrimidine moiety were synthesized by the method of active substructure combination. The structures of the title compounds were characterized by 1H NMR, 13C NMR, MS and elemental analysis. Preliminary bioassay data displayed that some target compounds showed certain insecticidal activities. At the concentration of 500 μg/mL, compounds 6b and 6c exhibited 60% and 70% insecticidal activity against Aphis craccivora, compounds 6a, 6b, 6c, and 6d had 100%, 100%, 100% and 90% insecticidal activity against Nilaparvata lugens. When the concentration was reduced to 100 μg/mL, compounds 6a, 6b and 6d were still active against Nilaparvata lugens with inhibitory values of 60%, 60% and 50%, respectively. In addition, insecticidal activities against Oriental armyworm of compounds 6f, 6g and 6m were 80%, 70% and 90%, respectively, at 500 μg/mL.
2017, 37(4): 1027-1032
doi: 10.6023/cjoc201611027
Abstract:
Poly[(S)-3-acrylamide-2, 2'-dihydroxy-1, 1'-binaphthyl] (poly-6) was synthesized through radical polymerization and applied in the asymmetric addition of diethylzinc to aromatic aldehydes, giving the optically active products up to 95% enantiomeric excess (ee). Besides, The poly-6 could be recycled up to six times without erosion of the enantioselectivity.
Poly[(S)-3-acrylamide-2, 2'-dihydroxy-1, 1'-binaphthyl] (poly-6) was synthesized through radical polymerization and applied in the asymmetric addition of diethylzinc to aromatic aldehydes, giving the optically active products up to 95% enantiomeric excess (ee). Besides, The poly-6 could be recycled up to six times without erosion of the enantioselectivity.
2017, 37(4): 1033-1039
doi: 10.6023/cjoc201612039
Abstract:
Totally 21 compounds were isolated from the EtOAc extract of fermentation broth of fungus Xylaria polymorpha (Pers.: Fr.) Grer, including two new drimane-type sesquiterpenoids named polymorphines A and B (1~2) and one new phenyloxolane compound named 2-methyl-2-(4-hydroxymethylphenyl) oxolane (3), together with 18 known compounds 4~21. The structures of these compounds were elucidated by NMR and single-crystal X-ray diffraction analysis. Compound 2 exhibited anti-acetylcholinesterase and α-glucosidase inhibitory activities. Moreover, compound 3 showed moderate inhibitory activitiy against the nematode Panagrellus redivivus with mortality ratio of 59.6% at 2.5 mg/mL.
Totally 21 compounds were isolated from the EtOAc extract of fermentation broth of fungus Xylaria polymorpha (Pers.: Fr.) Grer, including two new drimane-type sesquiterpenoids named polymorphines A and B (1~2) and one new phenyloxolane compound named 2-methyl-2-(4-hydroxymethylphenyl) oxolane (3), together with 18 known compounds 4~21. The structures of these compounds were elucidated by NMR and single-crystal X-ray diffraction analysis. Compound 2 exhibited anti-acetylcholinesterase and α-glucosidase inhibitory activities. Moreover, compound 3 showed moderate inhibitory activitiy against the nematode Panagrellus redivivus with mortality ratio of 59.6% at 2.5 mg/mL.
2017, 37(4): 1040-1045
doi: 10.6023/cjoc201611025
Abstract:
A new method for the synthesis of 2-benzoylated 2H-azirine via Cu-promoted oxidative cyclization/migration of enaminone was reported. The advantage of our approach is mild reaction condition, short reaction time and easy operation.
A new method for the synthesis of 2-benzoylated 2H-azirine via Cu-promoted oxidative cyclization/migration of enaminone was reported. The advantage of our approach is mild reaction condition, short reaction time and easy operation.
2017, 37(4): 1046-1050
doi: 10.6023/cjoc201608011
Abstract:
Peach twig borer is one of the most serious pests, whose sex pheromone is 5E-decen-1-ol and 5E-decenyl acetate. Synthesis of both compounds was achieved from acrolein. Firstly, a tandem addition reaction of acrolein with acetylene in the presence of Pd (OAc)2 gave 5-bromo-4E-pentenal, which reacted with the ylide prepared from (methoxymethyl) triphenyl-phodphonium chloride to afford (1E, 5E/Z)-1-bromo-6-methoxyhexadiene. The compound was coupled with Grignard reagent, followed by hydrolysis and reduction to give 5E-decen-1-ol. Esterification of the alcohol afforded 5E-decenyl acetate.
Peach twig borer is one of the most serious pests, whose sex pheromone is 5E-decen-1-ol and 5E-decenyl acetate. Synthesis of both compounds was achieved from acrolein. Firstly, a tandem addition reaction of acrolein with acetylene in the presence of Pd (OAc)2 gave 5-bromo-4E-pentenal, which reacted with the ylide prepared from (methoxymethyl) triphenyl-phodphonium chloride to afford (1E, 5E/Z)-1-bromo-6-methoxyhexadiene. The compound was coupled with Grignard reagent, followed by hydrolysis and reduction to give 5E-decen-1-ol. Esterification of the alcohol afforded 5E-decenyl acetate.
