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2019 Volume 39 Issue 4
Progress in Imine Formation from Direct Coupling of Alcohols and Amines Catalyzed by Metal Catalysts
2019, 39(4): 883-902
doi: 10.6023/cjoc201808039
Abstract:
Imines are very important class of compounds and have been widely utilized in fine chemicals, pharmaceuticals and chemical industry. The C=N double bond in imine is an important nitrogen source in different types of reactions due to its high reactive activity. Due to its high atom economy, catalytic direct coupling of alcohols and amines to imines based on metal catalysts has attracted much attention and maken great progress in recent years. In this paper, the advances in direct coupling of alcohols and amines to imines catalyzed by metal catalysts are reviewed.
Imines are very important class of compounds and have been widely utilized in fine chemicals, pharmaceuticals and chemical industry. The C=N double bond in imine is an important nitrogen source in different types of reactions due to its high reactive activity. Due to its high atom economy, catalytic direct coupling of alcohols and amines to imines based on metal catalysts has attracted much attention and maken great progress in recent years. In this paper, the advances in direct coupling of alcohols and amines to imines catalyzed by metal catalysts are reviewed.
Recent Developments in Protein Engineering and Catalytic Oxidations of Baeyer-Villiger Monooxygenase
2019, 39(4): 903-915
doi: 10.6023/cjoc201810023
Abstract:
Baeyer-Villiger monooxygenase (BVMO) is an important biocatalyst for Baeyer-Villiger oxidation of various organic ketone/aldehyde compounds, and sulfur, selenium, or boron-containing heteroatoms compounds. As an indispensable tool, BVMO-catalyzed oxidation displays some advantages, such as high selectivity, mild reaction conditions and high efficiency, leading to wide applications into the synthesis of chiral compounds. In recent years, bioinformatics analysis and genome mining have been used to find more novel BVMOs from microorganisms. Besides natural substrates, these BVMOs can accept various organic compounds showing wide substrate scope. Meanwhile, protein engineering has been widely used to improve the catalytic performance of BVMOs, such as the expanded substrate scope, high thermostability and activity, high stereo-, regio-and chemo-selectivities. Based on the Baeyer-Villiger oxidation reaction with different substrate structures, the recent advancements in the research on the catalytic oxidation of wild type and protein-engineered BVMOs in the past five years are summarized.
Baeyer-Villiger monooxygenase (BVMO) is an important biocatalyst for Baeyer-Villiger oxidation of various organic ketone/aldehyde compounds, and sulfur, selenium, or boron-containing heteroatoms compounds. As an indispensable tool, BVMO-catalyzed oxidation displays some advantages, such as high selectivity, mild reaction conditions and high efficiency, leading to wide applications into the synthesis of chiral compounds. In recent years, bioinformatics analysis and genome mining have been used to find more novel BVMOs from microorganisms. Besides natural substrates, these BVMOs can accept various organic compounds showing wide substrate scope. Meanwhile, protein engineering has been widely used to improve the catalytic performance of BVMOs, such as the expanded substrate scope, high thermostability and activity, high stereo-, regio-and chemo-selectivities. Based on the Baeyer-Villiger oxidation reaction with different substrate structures, the recent advancements in the research on the catalytic oxidation of wild type and protein-engineered BVMOs in the past five years are summarized.
2019, 39(4): 916-928
doi: 10.6023/cjoc201807055
Abstract:
Sulfhydryl compounds, such as cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and so on, play an important role in the normal human physiological processes. Molecular fluorescent probes have attracted much attention of scholar in the detection of sulfhydryl compounds, since it has the advantage of good selectivity, high sensitivity, good biocompatibility and real-time in situ monitoring. At present, the design of thiol-based fluorescent probes is mainly based on the strong nucleophilicity of sulfhydryl groups. In this paper, the synthesis of fluorescent probes for detecting sulfhydryl compounds, which was reported from 2013 to 2018, is reviewed based on the different mechanism of the reaction between fluorescence probe and sulfhydryl, including Michael addition, cyclization of aldehyde groups, sulfonamides or sulfonates of the lysis, natural chemical linkage and so on. The detection limit of the probe, response time, equivalence ratio were elaborated.
Sulfhydryl compounds, such as cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and so on, play an important role in the normal human physiological processes. Molecular fluorescent probes have attracted much attention of scholar in the detection of sulfhydryl compounds, since it has the advantage of good selectivity, high sensitivity, good biocompatibility and real-time in situ monitoring. At present, the design of thiol-based fluorescent probes is mainly based on the strong nucleophilicity of sulfhydryl groups. In this paper, the synthesis of fluorescent probes for detecting sulfhydryl compounds, which was reported from 2013 to 2018, is reviewed based on the different mechanism of the reaction between fluorescence probe and sulfhydryl, including Michael addition, cyclization of aldehyde groups, sulfonamides or sulfonates of the lysis, natural chemical linkage and so on. The detection limit of the probe, response time, equivalence ratio were elaborated.
2019, 39(4): 929-939
doi: 10.6023/cjoc201810033
Abstract:
Organic molecules containing trifluoromethyl groups often exhibit unique physical and chemical properties, and have found extensive applications. Trifluoroacetic acid and its derivatives have advantages including low cost, ready availability and high stability. Furthermore, CO2 is the byproduct. Therefore, trifluoroacetic acid and its derivatives are ideal trifluoromethylating reagents, and have great application potentials. The progress of trifluoromethylation reactions using trifluoroacetic acid and its derivatives as CF3-sources is reviewed, including the reactions of C-X (X=Br and I), C-H, and C=X (X=C, O). The mechanisms are also introduced.
Organic molecules containing trifluoromethyl groups often exhibit unique physical and chemical properties, and have found extensive applications. Trifluoroacetic acid and its derivatives have advantages including low cost, ready availability and high stability. Furthermore, CO2 is the byproduct. Therefore, trifluoroacetic acid and its derivatives are ideal trifluoromethylating reagents, and have great application potentials. The progress of trifluoromethylation reactions using trifluoroacetic acid and its derivatives as CF3-sources is reviewed, including the reactions of C-X (X=Br and I), C-H, and C=X (X=C, O). The mechanisms are also introduced.
2019, 39(4): 940-951
doi: 10.6023/cjoc201810021
Abstract:
Endoplasmic reticulum (ER) is an important organelle in eukaryotic cells and participates in the synthesis and secretion of various proteins, glycogen, lipids, and cholesterol substances. It is surrounded by a single membrane in the cytoplasm, which is a three-dimensional mesh structure formed by flat cysts, membrane tubes, and bubbles. Research on the physiological morphology of ER can facilitate the resolution of certain metabolic diseases. Due to the good optical properties and outstanding specific localization, fluorescent probe technology has been widely used in structural investigation and activity tracking of organelles. The ER fluorescent probes can be divided into two types, one is a single functional ER localization probe, the other is a multi-functional ER probe, which has multiple functions of locating and detecting active species in ER, the morphology and environment of ER. In this article, the structure, function and biological application of ER fluorescent probes in recent years are summarized and reviewed. Various localization mechanisms of ER fluorescent probes are described. The development trend of ER fluorescent probes in life science research is prospected.
Endoplasmic reticulum (ER) is an important organelle in eukaryotic cells and participates in the synthesis and secretion of various proteins, glycogen, lipids, and cholesterol substances. It is surrounded by a single membrane in the cytoplasm, which is a three-dimensional mesh structure formed by flat cysts, membrane tubes, and bubbles. Research on the physiological morphology of ER can facilitate the resolution of certain metabolic diseases. Due to the good optical properties and outstanding specific localization, fluorescent probe technology has been widely used in structural investigation and activity tracking of organelles. The ER fluorescent probes can be divided into two types, one is a single functional ER localization probe, the other is a multi-functional ER probe, which has multiple functions of locating and detecting active species in ER, the morphology and environment of ER. In this article, the structure, function and biological application of ER fluorescent probes in recent years are summarized and reviewed. Various localization mechanisms of ER fluorescent probes are described. The development trend of ER fluorescent probes in life science research is prospected.
2019, 39(4): 952-960
doi: 10.6023/cjoc201811006
Abstract:
Fluorescence detection based on excited state intramolecular proton transfer (ESIPT) using reaction-based probes has attracted considerable attention in the scientific community as they offers promising advantages, including high selectivity, high sensitivity and large Stoke shift. The representative examples of design strategies, mechanism of actions, existing challenges and future developments for reaction-based ESIPT fluorophores reported in the last ten years are reviewed.
Fluorescence detection based on excited state intramolecular proton transfer (ESIPT) using reaction-based probes has attracted considerable attention in the scientific community as they offers promising advantages, including high selectivity, high sensitivity and large Stoke shift. The representative examples of design strategies, mechanism of actions, existing challenges and future developments for reaction-based ESIPT fluorophores reported in the last ten years are reviewed.
2019, 39(4): 961-973
doi: 10.6023/cjoc201809031
Abstract:
Amide motifs are prevalent structures found in natural products, pharmaceuticals, and bioactive compounds. Amide bond formations are the most important transformations in organic chemistry. Beckmann rearrangement is a significant method for the synthesis of primary and secondary amides. Recently, diversified new catalytic protocols were developed, including one-pot reaction from the corresponding aldehydes and ketones, or even from alcohols. The progress and applications of Beckmann rearrangement in recent five years are reviewed.
Amide motifs are prevalent structures found in natural products, pharmaceuticals, and bioactive compounds. Amide bond formations are the most important transformations in organic chemistry. Beckmann rearrangement is a significant method for the synthesis of primary and secondary amides. Recently, diversified new catalytic protocols were developed, including one-pot reaction from the corresponding aldehydes and ketones, or even from alcohols. The progress and applications of Beckmann rearrangement in recent five years are reviewed.
2019, 39(4): 974-981
doi: 10.6023/cjoc201808018
Abstract:
More and more attention has been focused on acyclic nucleoside phosphonates (ANPs) antiviral agents which were wildly used in clinical therapy. However, poor oral bioavailability and high toxicity directly related to the phosphonate charge were serious and unnegligible especially for the treatment of chronic diseases such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Preparing appropriate forms of prodrug could enhance the oral bioavailability and reduce the toxicity because of the smooth absorption of prodrugs and the release of active drug only at the target. This review summarizes some recent progress in prodrugs of ANPs antiviral agents based on the structures of tenofovir, adefovir and cidofovir.
More and more attention has been focused on acyclic nucleoside phosphonates (ANPs) antiviral agents which were wildly used in clinical therapy. However, poor oral bioavailability and high toxicity directly related to the phosphonate charge were serious and unnegligible especially for the treatment of chronic diseases such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Preparing appropriate forms of prodrug could enhance the oral bioavailability and reduce the toxicity because of the smooth absorption of prodrugs and the release of active drug only at the target. This review summarizes some recent progress in prodrugs of ANPs antiviral agents based on the structures of tenofovir, adefovir and cidofovir.
2019, 39(4): 982-1012
doi: 10.6023/cjoc201810006
Abstract:
The microbe is an important source of lead compound. It plays an important role in drug development. Many new active compounds were found from actinomycetes, and the number of new compounds from rare actinomycetes showed an upward trend. This paper introduces the new active compounds including 515 new natural products found in rare actinomycetes, from plants, soil, marine sediment, marine animals and so on. The structure type included macrolides, polyketides, anthraquinones, bipyridines, polyene, etc. The biotransformation of natural products by rare actinomycetes was reported from January 2006 to June 2018.
The microbe is an important source of lead compound. It plays an important role in drug development. Many new active compounds were found from actinomycetes, and the number of new compounds from rare actinomycetes showed an upward trend. This paper introduces the new active compounds including 515 new natural products found in rare actinomycetes, from plants, soil, marine sediment, marine animals and so on. The structure type included macrolides, polyketides, anthraquinones, bipyridines, polyene, etc. The biotransformation of natural products by rare actinomycetes was reported from January 2006 to June 2018.
2019, 39(4): 1013-1022
doi: 10.6023/cjoc201809025
Abstract:
A novel benzimidazole-hydrazone derivative, N'-(2-hydroxy-1-naphthyl)methylene-2-[2-(4-methylphenylsulfonyl-methyl)-1H-benzoimidazol-1-yl]acetohydrazide (L), was synthesized and characterized by IR, 1H NMR, 13C NMR, HRMS and elemental analysis. The recognition properties of L for anions were studied by naked eye, ultraviolet-vis and fluorescence spectroscopy. The results showed that the color of the solution changes from colorless to bright yellow upon addition of F-, AcO- and H2PO4- to the CH3CN solution of compound L. The solution of L emitted yellow fluorescence after the addition of F- and AcO- under the UV lamp (λ=365 nm). It indicated that compound L can be used as a probe for the naked eye to recognize F-, AcO- and H2PO4-. The experimental results of UV and fluorescence spectroscopy showed that the probe L can recognize F- and AcO- with high selectivity and sensitivity. The binding constants (Ka) of probe L to F- and AcO- were 4.25×103 and 2.96×104 L·mol-1, respectively. The detection limits (DL) were 3.63×10-7 and 8.51×10-8 mol·L-1, respectively. The stoichiometry of complexation between L and F-/AcO- was 1:1, which was supported by the Job's plot and density functional theory (DFT) calculations. The mechanism of binding of L with F-/AcO- was established by 1H NMR titration. The results showed that compound L can be used as a colorimetric and fluorescent probe for detecting F- and AcO-.
A novel benzimidazole-hydrazone derivative, N'-(2-hydroxy-1-naphthyl)methylene-2-[2-(4-methylphenylsulfonyl-methyl)-1H-benzoimidazol-1-yl]acetohydrazide (L), was synthesized and characterized by IR, 1H NMR, 13C NMR, HRMS and elemental analysis. The recognition properties of L for anions were studied by naked eye, ultraviolet-vis and fluorescence spectroscopy. The results showed that the color of the solution changes from colorless to bright yellow upon addition of F-, AcO- and H2PO4- to the CH3CN solution of compound L. The solution of L emitted yellow fluorescence after the addition of F- and AcO- under the UV lamp (λ=365 nm). It indicated that compound L can be used as a probe for the naked eye to recognize F-, AcO- and H2PO4-. The experimental results of UV and fluorescence spectroscopy showed that the probe L can recognize F- and AcO- with high selectivity and sensitivity. The binding constants (Ka) of probe L to F- and AcO- were 4.25×103 and 2.96×104 L·mol-1, respectively. The detection limits (DL) were 3.63×10-7 and 8.51×10-8 mol·L-1, respectively. The stoichiometry of complexation between L and F-/AcO- was 1:1, which was supported by the Job's plot and density functional theory (DFT) calculations. The mechanism of binding of L with F-/AcO- was established by 1H NMR titration. The results showed that compound L can be used as a colorimetric and fluorescent probe for detecting F- and AcO-.
2019, 39(4): 1023-1028
doi: 10.6023/cjoc201809028
Abstract:
Trivalent chromium (Cr3+) plays an important role in the metabolismof fats, nucleic acids, carbohydrates and proteins. Moreover, Cr3+ is considered to be a carcinogen and is extremely harmful to humans. Therefore, Cr3+ fluorescent probe L was synthesized by reaction of 8-hydroxyquinolinaldehyde with thiocarbazone. The probe L showed high selectivity towards Cr3+ ion through the color of solution changed from colorless to yellow for naked-eye detection and significant fluorescence intensity enhanced in CH3CN/H2O (V:V=1:2, Tris buffer 50 mmol/L, pH=7.3) solution. The 1:1 binding stoichiometry between probe and Cr3+ was determined from Job's plot, fluorescence titration, ESI-MS and density functional theory (DFT) calculations. The association constant (Ka) and the detection limit for Cr3+ were found to be to be 1.00×105 and 2.85×10-7 mol/L, respectively. Moreover, bioimaging experiments showed that L could sense Cr3+ ion in living cells with a fluorescence enhancement signal.
Trivalent chromium (Cr3+) plays an important role in the metabolismof fats, nucleic acids, carbohydrates and proteins. Moreover, Cr3+ is considered to be a carcinogen and is extremely harmful to humans. Therefore, Cr3+ fluorescent probe L was synthesized by reaction of 8-hydroxyquinolinaldehyde with thiocarbazone. The probe L showed high selectivity towards Cr3+ ion through the color of solution changed from colorless to yellow for naked-eye detection and significant fluorescence intensity enhanced in CH3CN/H2O (V:V=1:2, Tris buffer 50 mmol/L, pH=7.3) solution. The 1:1 binding stoichiometry between probe and Cr3+ was determined from Job's plot, fluorescence titration, ESI-MS and density functional theory (DFT) calculations. The association constant (Ka) and the detection limit for Cr3+ were found to be to be 1.00×105 and 2.85×10-7 mol/L, respectively. Moreover, bioimaging experiments showed that L could sense Cr3+ ion in living cells with a fluorescence enhancement signal.
2019, 39(4): 1029-1036
doi: 10.6023/cjoc201811030
Abstract:
Protein tyrosine phosphatase 1B (PTP1B) inhibitor has recently been identified as new candidate drug for type Ⅱ diabetes and obesity due to it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphosphonate-based pTyr mimetics, a series of novel chalcone derivatives bearing 1H-benzo[d]imidazol or 1H-benzo[d] [1,2,3]-triazol moieties were designed, synthesized, and evaluated for their PTP1B inhibitory activities. The results demonstrated that all compounds presented potent inhibitory activities against PTP1B, among which 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-(naphthalen-2-yl)-3-oxoprop-1-en-1-yl)benzylidene)acetohydrazide (10i) exhibited the best potency with IC50 value of (2.98±0.04) μmol·L-1. Importantly, 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-oxo-3-(p-tolyl)prop-1-en-1-yl)benzylidene)-acetohydrazide (10h) showed no significant inhibition on T-cell protein tyrosine phosphatase (TCPTP) at the concentration of 20 μg/mL, suggesting the highly selectivity of this agent toward PTP1B.
Protein tyrosine phosphatase 1B (PTP1B) inhibitor has recently been identified as new candidate drug for type Ⅱ diabetes and obesity due to it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphosphonate-based pTyr mimetics, a series of novel chalcone derivatives bearing 1H-benzo[d]imidazol or 1H-benzo[d] [1,2,3]-triazol moieties were designed, synthesized, and evaluated for their PTP1B inhibitory activities. The results demonstrated that all compounds presented potent inhibitory activities against PTP1B, among which 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-(naphthalen-2-yl)-3-oxoprop-1-en-1-yl)benzylidene)acetohydrazide (10i) exhibited the best potency with IC50 value of (2.98±0.04) μmol·L-1. Importantly, 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-oxo-3-(p-tolyl)prop-1-en-1-yl)benzylidene)-acetohydrazide (10h) showed no significant inhibition on T-cell protein tyrosine phosphatase (TCPTP) at the concentration of 20 μg/mL, suggesting the highly selectivity of this agent toward PTP1B.
2019, 39(4): 1037-1043
doi: 10.6023/cjoc201808016
Abstract:
Following the principle of union of active group, the thiochromanone was combined with 1, 3, 4-oxadiazole, and 12 compounds were designed and synthesized. The target compounds were confirmed by 1H NMR and HRMS. The preliminary antifungal activity assay showed that most of the target compounds exhibited significant inhibition activity against four animal pathogenic fungi and four plant pathogenic fungi. Among them, the minimum inhibitory concentration (MIC) value of compound 4f against Canidia albicans reached 4 μg·mL-1, and the MIC value of 4d against Aspergillusnigervan tiegh reached 8 μg·mL-1, which were higher than the positive controls. And the molecular docking studies have found that 4f has strong binding ability to CYP51 of Canidia albicans, which may be a potential CYP51 inhibitor.
Following the principle of union of active group, the thiochromanone was combined with 1, 3, 4-oxadiazole, and 12 compounds were designed and synthesized. The target compounds were confirmed by 1H NMR and HRMS. The preliminary antifungal activity assay showed that most of the target compounds exhibited significant inhibition activity against four animal pathogenic fungi and four plant pathogenic fungi. Among them, the minimum inhibitory concentration (MIC) value of compound 4f against Canidia albicans reached 4 μg·mL-1, and the MIC value of 4d against Aspergillusnigervan tiegh reached 8 μg·mL-1, which were higher than the positive controls. And the molecular docking studies have found that 4f has strong binding ability to CYP51 of Canidia albicans, which may be a potential CYP51 inhibitor.
2019, 39(4): 1044-1052
doi: 10.6023/cjoc201810019
Abstract:
A series of novel arylpyridone hydrazones were designed and synthesized by using arylpyridinylmethanone as the plug-in molecules and ferimzone as parent compound. The structure of the products were confirmed by 1H NMR, 13C NMR and HRMS. The antifungal activities of all compounds were tested by growth rate method in vitro. The results showed that most of the compounds inhibited eight selected pathogens at the concentration of 70 μmol/L. The inhibitory effect of 2'-methylacetylbenzene-4, 6-dimethoxypyrimidine-2-hydrazone (Ⅲ-3) and 2-(2'-((4'-bromo-phenyl)(3'-chloro-pyridine-4'-yl)-methylene-hydrazine)-4, 6-dimethoxypyrimidine (Ⅲ-18) on pathogenic fungi was significantly higher than that of ferimzone, in which compound Ⅲ-3 has a great degree of inhibition on Botrytis cinerea with EC50 value of 22.18 μmol/L, and EC50 value of compound Ⅲ-18 is less than 0.35 umol/L on Thanatephorus cucumeris, which is 260 times higher than that of control.
A series of novel arylpyridone hydrazones were designed and synthesized by using arylpyridinylmethanone as the plug-in molecules and ferimzone as parent compound. The structure of the products were confirmed by 1H NMR, 13C NMR and HRMS. The antifungal activities of all compounds were tested by growth rate method in vitro. The results showed that most of the compounds inhibited eight selected pathogens at the concentration of 70 μmol/L. The inhibitory effect of 2'-methylacetylbenzene-4, 6-dimethoxypyrimidine-2-hydrazone (Ⅲ-3) and 2-(2'-((4'-bromo-phenyl)(3'-chloro-pyridine-4'-yl)-methylene-hydrazine)-4, 6-dimethoxypyrimidine (Ⅲ-18) on pathogenic fungi was significantly higher than that of ferimzone, in which compound Ⅲ-3 has a great degree of inhibition on Botrytis cinerea with EC50 value of 22.18 μmol/L, and EC50 value of compound Ⅲ-18 is less than 0.35 umol/L on Thanatephorus cucumeris, which is 260 times higher than that of control.
2019, 39(4): 1053-1063
doi: 10.6023/cjoc201809015
Abstract:
New bifunctional chiral thiourea-amide organocatalysts were developed. Their applications in asymmetric conjugate addition of 2, 4-pentandione to various nitroalkenes were investigated. The corresponding adducts were obtained in excellent yields with high enantioselectivities up to 94% ee in present of 1 mol% catalyst. The catalytic system could also suit for various nitroalkenes bearing electron-donating or electron-withdrawing groups. The preliminary structure-activity relationship study reveals that the acyl group in pyrrolidine N position plays an important role in catalyzing the reaction.
New bifunctional chiral thiourea-amide organocatalysts were developed. Their applications in asymmetric conjugate addition of 2, 4-pentandione to various nitroalkenes were investigated. The corresponding adducts were obtained in excellent yields with high enantioselectivities up to 94% ee in present of 1 mol% catalyst. The catalytic system could also suit for various nitroalkenes bearing electron-donating or electron-withdrawing groups. The preliminary structure-activity relationship study reveals that the acyl group in pyrrolidine N position plays an important role in catalyzing the reaction.
2019, 39(4): 1064-1069
doi: 10.6023/cjoc201809003
Abstract:
Using the splicing principle of combining the pharmacological group triazene with 1, 3, 4-thiadiazole, 15 unreported 1, 3, 4-thiadiazole triazene derivatives were synthesized. The structures of the compounds were determined by nucleated magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). By using the typical triazene drug dacarbazine (DTIC) and drug 5-fluorouracil (5-FU) as a reference, the activity detections of human esop-hageal cancer cells (EC109), human gastric cancer cells (MGC803), and human prostate cancer cells (PC-3) were carried out. The results showed that some compounds inhibited human gastric cancer cells (MGC803) more strongly than dacarbazine (DTIC), and the IC50 values of compounds 2-(3-methyanilino)-5-[4-(3, 3-dimethyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8c), 2-(2-methoxyanilino)-5-[4-(3, 3-dimethyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8f), and 2-(3, 4-dichloroanilino)-5-[4-(3, 3-di-methyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8l) were lower than those of 5-fluorouracil with 5.3, 6.5 and 6.3 μmol/L, respec-tively. Some compounds inhibited human prostate cancer cells (PC-3) more strongly than dacarbazine (DTIC), and the IC50 value of 8l is lower than that of 5-fluorouracil with 13.5 μmol/L.
Using the splicing principle of combining the pharmacological group triazene with 1, 3, 4-thiadiazole, 15 unreported 1, 3, 4-thiadiazole triazene derivatives were synthesized. The structures of the compounds were determined by nucleated magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). By using the typical triazene drug dacarbazine (DTIC) and drug 5-fluorouracil (5-FU) as a reference, the activity detections of human esop-hageal cancer cells (EC109), human gastric cancer cells (MGC803), and human prostate cancer cells (PC-3) were carried out. The results showed that some compounds inhibited human gastric cancer cells (MGC803) more strongly than dacarbazine (DTIC), and the IC50 values of compounds 2-(3-methyanilino)-5-[4-(3, 3-dimethyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8c), 2-(2-methoxyanilino)-5-[4-(3, 3-dimethyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8f), and 2-(3, 4-dichloroanilino)-5-[4-(3, 3-di-methyltriazol-1-yl) phenyl]-1, 3, 4-thiadiazole (8l) were lower than those of 5-fluorouracil with 5.3, 6.5 and 6.3 μmol/L, respec-tively. Some compounds inhibited human prostate cancer cells (PC-3) more strongly than dacarbazine (DTIC), and the IC50 value of 8l is lower than that of 5-fluorouracil with 13.5 μmol/L.
2019, 39(4): 1070-1078
doi: 10.6023/cjoc201809011
Abstract:
A novel copper-catalyzed oxidative cross-coupling reaction between N-arylglycine esters and Silyl enol ethers for the synthesis of β-acyl-α-amino acid esters has been developed. The features of this reaction are high reaction yields, mild reaction conditions (such as room temperature environments and inexpensive catalysts, etc.) and smooth operation in aqueous medium.
A novel copper-catalyzed oxidative cross-coupling reaction between N-arylglycine esters and Silyl enol ethers for the synthesis of β-acyl-α-amino acid esters has been developed. The features of this reaction are high reaction yields, mild reaction conditions (such as room temperature environments and inexpensive catalysts, etc.) and smooth operation in aqueous medium.
2019, 39(4): 1079-1084
doi: 10.6023/cjoc201811017
Abstract:
The synthesis of the AC ring moiety of daphnilactone B has been achieved through an efficient Diels-Alder reaction and Au-catalyzed Conia-ene reaction in seven steps with 30% overall yield.Our strategies paved the way to the total synthesis of various daphnilactone B-type Daphniphyllum alkaloids.
The synthesis of the AC ring moiety of daphnilactone B has been achieved through an efficient Diels-Alder reaction and Au-catalyzed Conia-ene reaction in seven steps with 30% overall yield.Our strategies paved the way to the total synthesis of various daphnilactone B-type Daphniphyllum alkaloids.
2019, 39(4): 1085-1094
doi: 10.6023/cjoc201809042
Abstract:
A series of 5-aminochromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 4a~4w were synthesized by three-component reactions of salicylaldehydes, ethyl cyanoacetate and 5-aminopyrazoles catalyzed by triethylamine (TEA). The properties of the synthesized compounds were examined by fluorescence spectroscopy and the results indicated that some compounds were possessed high fluorescence quantum yields.
A series of 5-aminochromeno[4, 3-d]pyrazolo[3, 4-b]pyridin-6(3H)-one derivatives 4a~4w were synthesized by three-component reactions of salicylaldehydes, ethyl cyanoacetate and 5-aminopyrazoles catalyzed by triethylamine (TEA). The properties of the synthesized compounds were examined by fluorescence spectroscopy and the results indicated that some compounds were possessed high fluorescence quantum yields.
C—C Triple Bond Cleavage/Rearrangement Reaction for Accessing 2, 4, 4-Trichloronaphthalen-1(4H)-ones
2019, 39(4): 1095-1101
doi: 10.6023/cjoc201811015
Abstract:
N-Chlorosuccinimide (NCS)-mediated[2+2] cycloaddition and C-C triple bond cleavage/rearrangement reaction of yne-allenones and H2O as a nucleophilic reagent enabled the formation of 18 examples of 2, 4, 4-trichloronaphthalene-1(4H)-one derivatives with 55%~88% yields. The structures of these obtainable products were based on their NMR, IR and HRMS data, among which the structure of product 2e was confirmed by X-ray analysis. This metal-free transformation features mild conditions, simple operation and high reaction yields. It provides an effective and new protocol for the synthesis of trichloro-substituted naphthalene-1(4H)-ones.
N-Chlorosuccinimide (NCS)-mediated[2+2] cycloaddition and C-C triple bond cleavage/rearrangement reaction of yne-allenones and H2O as a nucleophilic reagent enabled the formation of 18 examples of 2, 4, 4-trichloronaphthalene-1(4H)-one derivatives with 55%~88% yields. The structures of these obtainable products were based on their NMR, IR and HRMS data, among which the structure of product 2e was confirmed by X-ray analysis. This metal-free transformation features mild conditions, simple operation and high reaction yields. It provides an effective and new protocol for the synthesis of trichloro-substituted naphthalene-1(4H)-ones.
2019, 39(4): 1102-1108
doi: 10.6023/cjoc201811007
Abstract:
α-Haloamides are a very important class of carbonyl compounds, and widely exist in a range of natural products and bioactive molecules. Herein, the realization of the tandem oxidation/halogenation of ynamides by employing the zinc halide as both the catalyst and the halogen source is described, thus avoiding the use of other external halogenating reagents. This method allows the practical synthesis of a variety of valuable α-haloamides in moderate to good yields.
α-Haloamides are a very important class of carbonyl compounds, and widely exist in a range of natural products and bioactive molecules. Herein, the realization of the tandem oxidation/halogenation of ynamides by employing the zinc halide as both the catalyst and the halogen source is described, thus avoiding the use of other external halogenating reagents. This method allows the practical synthesis of a variety of valuable α-haloamides in moderate to good yields.
2019, 39(4): 1109-1115
doi: 10.6023/cjoc201809020
Abstract:
A highly efficient protocol for the transamidation of N, N-dimethylformamide (DMF) and amines has been developed, utilizing a catalytic amount Pd(OAc)2. This methodology has a broad substrate scope for aliphatic, aromatic, and heterocyclic amines. And this process is simple and easily performed without solvent and co-catalyst.
A highly efficient protocol for the transamidation of N, N-dimethylformamide (DMF) and amines has been developed, utilizing a catalytic amount Pd(OAc)2. This methodology has a broad substrate scope for aliphatic, aromatic, and heterocyclic amines. And this process is simple and easily performed without solvent and co-catalyst.
2019, 39(4): 1122-1128
doi: 10.6023/cjoc201809001
Abstract:
Based on fully analyzing the mechanism of Beckmann rearrangement reaction, protonated amino functional mesoporous silica materials HAF-SBA-15 were obtained via acidizing amino functional mesoporous silica. The binding force between hydroxamic hydroxyl group and N was synergistically weakened by the coordination bond formed by proton hydrogen in HAF-SBA-15, lone pair electrons in hydroxyl hydroxoxoxime and hydrogen bonds formed between N, H and O. It synergistically weakenef the binding force between oxime hydroxyl and N, accelerated the departure of oxime hydroxyl and the formation of carbon positive ions, , and promoted the Beckmann rearrangement reaction. Catalyzed by HAF-SBA-15, N-benzo-phenamide was synthesized via the Beckmann rearrangement of diphenyl-ketoxime. The results showed that the conversion rate of diphenyl-ketoxime is high and the obtained N-benzophenamide is pure. Furthermore, effect of solvent type, reaction temperature, and catalyst dosage on the Beckmann rearrangement of diphenyl-ketoxime was investigated, and the optimum reaction conditions were obtained. The results illustrated that the optimum reaction conditions are mild because Beckmann rearrangement of diphenyl-ketoxime was efficiently carried out at 50℃.
Based on fully analyzing the mechanism of Beckmann rearrangement reaction, protonated amino functional mesoporous silica materials HAF-SBA-15 were obtained via acidizing amino functional mesoporous silica. The binding force between hydroxamic hydroxyl group and N was synergistically weakened by the coordination bond formed by proton hydrogen in HAF-SBA-15, lone pair electrons in hydroxyl hydroxoxoxime and hydrogen bonds formed between N, H and O. It synergistically weakenef the binding force between oxime hydroxyl and N, accelerated the departure of oxime hydroxyl and the formation of carbon positive ions, , and promoted the Beckmann rearrangement reaction. Catalyzed by HAF-SBA-15, N-benzo-phenamide was synthesized via the Beckmann rearrangement of diphenyl-ketoxime. The results showed that the conversion rate of diphenyl-ketoxime is high and the obtained N-benzophenamide is pure. Furthermore, effect of solvent type, reaction temperature, and catalyst dosage on the Beckmann rearrangement of diphenyl-ketoxime was investigated, and the optimum reaction conditions were obtained. The results illustrated that the optimum reaction conditions are mild because Beckmann rearrangement of diphenyl-ketoxime was efficiently carried out at 50℃.
2019, 39(4): 1116-1121
doi: 10.6023/cjoc201810002
Abstract:
A facile and efficient I2O5 promoted iodosulfonylation of alkynes for direct synthesis of (E)-β-iodovinyl sulfones is described. This procedure affords various synthetically useful β-iodosulfonyl alkenes in moderate to good yields under peroxide free conditions.
A facile and efficient I2O5 promoted iodosulfonylation of alkynes for direct synthesis of (E)-β-iodovinyl sulfones is described. This procedure affords various synthetically useful β-iodosulfonyl alkenes in moderate to good yields under peroxide free conditions.
2019, 39(4): 1129-1135
doi: 10.6023/cjoc201809018
Abstract:
Stereoselective Mizoroki-Heck arylation of (E)-7-methylocta-2, 6-dienoic acid with aryl iodide catalyzed by Pd(OAc)2 and P(o-MeC6H4)3 was optimized, and the yields were improved under the condition of excess Et3N both as the base and solvent with reduced amount of catalysts. Twenty (E)-3-aryl-7-methylocta-2, 6-dienoic acids were directly synthesized via Mizoroki-Heck arylation in 37%~68% isolated yields at reflux temperature. Their structures were characterized by IR, 1H, 13C NMR, HR-ESI-MS data and X-ray diffraction.
Stereoselective Mizoroki-Heck arylation of (E)-7-methylocta-2, 6-dienoic acid with aryl iodide catalyzed by Pd(OAc)2 and P(o-MeC6H4)3 was optimized, and the yields were improved under the condition of excess Et3N both as the base and solvent with reduced amount of catalysts. Twenty (E)-3-aryl-7-methylocta-2, 6-dienoic acids were directly synthesized via Mizoroki-Heck arylation in 37%~68% isolated yields at reflux temperature. Their structures were characterized by IR, 1H, 13C NMR, HR-ESI-MS data and X-ray diffraction.
2019, 39(4): 1136-1141
doi: 10.6023/cjoc201811026
Abstract:
Four new compounds, penicmariae-crucis A (1), penicmariae-crucis B (2), penicmariae-crucis C (3), penicmariae-crucis D (4), and a new natural product, (E)-2-methylhex-3-enedioic acid (5), together with five known compounds, O-methylcurvulinic acid (6), methyl 2-acetyl-3-hydroxy-5-methoxyphenylacetate (7), methyl 2-acetyl-3, 5-dihydroxyphenyl-acetate (8), β-sitosterol (9) and ergosterol peroxide (10), were isolated from the ethyl acetate extract of endophytic fungus Penicillium mariae-crucis in Paeonia lactiflora Pall. Their structures were established on the basis of extensive spectral analyses. All known compounds were isolated from P. mariae-crucis for the first time.
Four new compounds, penicmariae-crucis A (1), penicmariae-crucis B (2), penicmariae-crucis C (3), penicmariae-crucis D (4), and a new natural product, (E)-2-methylhex-3-enedioic acid (5), together with five known compounds, O-methylcurvulinic acid (6), methyl 2-acetyl-3-hydroxy-5-methoxyphenylacetate (7), methyl 2-acetyl-3, 5-dihydroxyphenyl-acetate (8), β-sitosterol (9) and ergosterol peroxide (10), were isolated from the ethyl acetate extract of endophytic fungus Penicillium mariae-crucis in Paeonia lactiflora Pall. Their structures were established on the basis of extensive spectral analyses. All known compounds were isolated from P. mariae-crucis for the first time.
2019, 39(4): 1142-1146
doi: 10.6023/cjoc201812005
Abstract:
Murrayaquinone A is a carbazolequinone alkaloid isolated from the root bark of Murraya euchrestifolia Hayata. It has been found to exhibit cardiotonic activity on heart muscle. Starting from the commercially available 3-acylindole, the total synthesis of Murrayaquinone A was realized in eight steps in an overall yield of 8%. The key step of our synthesis involves a palladium-catalyzed intramolecular α-C-H alkenylation of indole derivative to construct the carbazole A ring.
Murrayaquinone A is a carbazolequinone alkaloid isolated from the root bark of Murraya euchrestifolia Hayata. It has been found to exhibit cardiotonic activity on heart muscle. Starting from the commercially available 3-acylindole, the total synthesis of Murrayaquinone A was realized in eight steps in an overall yield of 8%. The key step of our synthesis involves a palladium-catalyzed intramolecular α-C-H alkenylation of indole derivative to construct the carbazole A ring.
2019, 39(4): 1147-1152
doi: 10.6023/cjoc201809038
Abstract:
Novel series of rearrangement reactions were herein reported that enable access to a variety of unique 2-aryl-3-(3'-oxobutenyl)-benzoxazole compounds 6a~6f from 2-aminophenol, aromatic aldehyde and 3-butyn-2-one as materials by nucleophilic conjugate addition, dehydration and rearrangement reactions and intramolecular cyclization in the presence of a catalytic amount of CH3COOH in CH2Cl2 at ambient temperature. On the basis of products and intermediate products, a series of possible mechanism was presented and theoretically verified by density functional theory (DFT) method at B3LYP/6-31G (d, p) level from both molecular energy and atomic charge in Gaussian 03 package. The results show that the theory and experiment consistently explain the rationality of the reaction mechanism. The mechanism of rearrangement provides a basis for further study of this type of reaction. The advantage of this method is that a novel structure of benzoxazole derivative was synthesized successfully via a series of rearrangement reactions. Therefore, this method can be used as an attractive strategy for practical synthesis of nitrogen heterocyclic compounds.
Novel series of rearrangement reactions were herein reported that enable access to a variety of unique 2-aryl-3-(3'-oxobutenyl)-benzoxazole compounds 6a~6f from 2-aminophenol, aromatic aldehyde and 3-butyn-2-one as materials by nucleophilic conjugate addition, dehydration and rearrangement reactions and intramolecular cyclization in the presence of a catalytic amount of CH3COOH in CH2Cl2 at ambient temperature. On the basis of products and intermediate products, a series of possible mechanism was presented and theoretically verified by density functional theory (DFT) method at B3LYP/6-31G (d, p) level from both molecular energy and atomic charge in Gaussian 03 package. The results show that the theory and experiment consistently explain the rationality of the reaction mechanism. The mechanism of rearrangement provides a basis for further study of this type of reaction. The advantage of this method is that a novel structure of benzoxazole derivative was synthesized successfully via a series of rearrangement reactions. Therefore, this method can be used as an attractive strategy for practical synthesis of nitrogen heterocyclic compounds.
2019, 39(4): 1153-1159
doi: 10.6023/cjoc201811010
Abstract:
Cu(OTf)2/AgOTf-catalyzed selective decarboxylation C-N crossing coupling of o-nitro aromatic carboxylic acids with o-aminobenzamides has been establised, affording seventeen diarylaminobenzamides in moderate yields. The present protocol provides a new choice for selective N-arylation of amines.
Cu(OTf)2/AgOTf-catalyzed selective decarboxylation C-N crossing coupling of o-nitro aromatic carboxylic acids with o-aminobenzamides has been establised, affording seventeen diarylaminobenzamides in moderate yields. The present protocol provides a new choice for selective N-arylation of amines.
2019, 39(4): 1160-1168
doi: 10.6023/cjoc201809040
Abstract:
A series of novel myricetin derivatives containing 1, 3, 4-oxadiazole moiety were designed and synthesized.Bioassays indicated that some compounds showed potential antibacterial and antiviral activities. Among them, compounds 4a, 4b, 4f and 4j demonstrated appreciable inhibitory effect against Xanthomonas axonopodis pv.citri (Xac), with half-maximal effective concentration (EC50) values of 18.5, 40.7, 26.9 and 32.4 μg/mL, which were significantly better than commercial agent bismerthiazol (68.8 μg/mL), compounds 4f and 4j also demonstrated appreciable inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with EC50 values of 45.9 and 35.7 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). In addition, compounds 4n demonstrated significant curative activity against TMV with EC50 value of 272.8 μg/mL, which was better than commercial agent ningnamycin (428.8 μg/mL), compounds 4f showed protecting activity against tobacco mosaic virus (TMV) with EC50 value of 235.6 μg/mL, which was better than commercial agent ningnamycin (447.9 μg/mL). Microscale thermophoresis (MST) indicated that compound 4j could bind with south rice black drawf virus P9-1.
A series of novel myricetin derivatives containing 1, 3, 4-oxadiazole moiety were designed and synthesized.Bioassays indicated that some compounds showed potential antibacterial and antiviral activities. Among them, compounds 4a, 4b, 4f and 4j demonstrated appreciable inhibitory effect against Xanthomonas axonopodis pv.citri (Xac), with half-maximal effective concentration (EC50) values of 18.5, 40.7, 26.9 and 32.4 μg/mL, which were significantly better than commercial agent bismerthiazol (68.8 μg/mL), compounds 4f and 4j also demonstrated appreciable inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with EC50 values of 45.9 and 35.7 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). In addition, compounds 4n demonstrated significant curative activity against TMV with EC50 value of 272.8 μg/mL, which was better than commercial agent ningnamycin (428.8 μg/mL), compounds 4f showed protecting activity against tobacco mosaic virus (TMV) with EC50 value of 235.6 μg/mL, which was better than commercial agent ningnamycin (447.9 μg/mL). Microscale thermophoresis (MST) indicated that compound 4j could bind with south rice black drawf virus P9-1.
2019, 39(4): 1175-1180
doi: 10.6023/cjoc201810005
Abstract:
A facile approach for thioetherification of 4-hydroxycoumarins with arylsulfonyl hydrazides promoted by tetrabutylammonium iodide in the presence of hydrochloric acid was developed generating a series of 3-arylthio-4-hydroxycoumarins in 65%~94% yields. Broad scope and easy availability of substrates, simple operation and high yields of products are the advantages of this method.
A facile approach for thioetherification of 4-hydroxycoumarins with arylsulfonyl hydrazides promoted by tetrabutylammonium iodide in the presence of hydrochloric acid was developed generating a series of 3-arylthio-4-hydroxycoumarins in 65%~94% yields. Broad scope and easy availability of substrates, simple operation and high yields of products are the advantages of this method.
2019, 39(4): 1169-1174
doi: 10.6023/cjoc201811018
Abstract:
The biosynthetic pathway of rifamycins is still not completely deciphered after decades of study. For example, the gene responsible for the oxidative elimination of C34a is not identified. It was proposed that some cytochrome P450 is related to this essential biosynthetic step in the modification of rifamycin. Here, cytochrome P450 encoding genes rif-orf0, 4 and 13 from rifamycin biosynthetic gene cluster were heterologously expressed in Streptomyces lividans and fed with 16-demethyl-34a-deoxyrifamycin W (1). Compound 1 was completely converted into 16-demethylrifamycin W (2) in the strain harboring rif-orf13. His6-tagged Orf13 was prepared from E. coli BL21 (DE3) and characterized to be active cytochrome P450. Enzymatic assays demonstrated that compound 1 could be converted into 2 by Orf13 as in vivo. Therefore, we concluded that rif-orf13 is responsible for the hydroxylation on C34a in the biosynthesis of rifamycins. In addition, it's role in vivo could be functionally complemented by rif-orf5, which encoding another cytochrome P450 enzyme.
The biosynthetic pathway of rifamycins is still not completely deciphered after decades of study. For example, the gene responsible for the oxidative elimination of C34a is not identified. It was proposed that some cytochrome P450 is related to this essential biosynthetic step in the modification of rifamycin. Here, cytochrome P450 encoding genes rif-orf0, 4 and 13 from rifamycin biosynthetic gene cluster were heterologously expressed in Streptomyces lividans and fed with 16-demethyl-34a-deoxyrifamycin W (1). Compound 1 was completely converted into 16-demethylrifamycin W (2) in the strain harboring rif-orf13. His6-tagged Orf13 was prepared from E. coli BL21 (DE3) and characterized to be active cytochrome P450. Enzymatic assays demonstrated that compound 1 could be converted into 2 by Orf13 as in vivo. Therefore, we concluded that rif-orf13 is responsible for the hydroxylation on C34a in the biosynthesis of rifamycins. In addition, it's role in vivo could be functionally complemented by rif-orf5, which encoding another cytochrome P450 enzyme.
2019, 39(4): 1181-1186
doi: 10.6023/cjoc201808032
Abstract:
A convenient method for improving the conversion and selectivity of aniline to azoxybenzene by adjusting the ratio of silicon to titanium of TS-1 is reported. Over TS-1 (80), aryl anilines are transformed into the corresponding azoxybenzenes in good yields with H2O2 as the oxidant. The effect of different reaction parameters like molar ratio of H2O2 to aniline, solvent and the activity in catalyst recycling has been studied.
A convenient method for improving the conversion and selectivity of aniline to azoxybenzene by adjusting the ratio of silicon to titanium of TS-1 is reported. Over TS-1 (80), aryl anilines are transformed into the corresponding azoxybenzenes in good yields with H2O2 as the oxidant. The effect of different reaction parameters like molar ratio of H2O2 to aniline, solvent and the activity in catalyst recycling has been studied.
2019, 39(4): 1187-1192
doi: 10.6023/cjoc201808011
Abstract:
New flavone derivatives are highly valued in drug discovery due to their diversity of important bioactivities. Herein, one simple Cu-catalyzed method of constructing C-Se bonds on flavone structures using convenient Se powder via C-H functionalization is reported, regioselectively affording ArSe-substituted flavone derivatives in good yields.
New flavone derivatives are highly valued in drug discovery due to their diversity of important bioactivities. Herein, one simple Cu-catalyzed method of constructing C-Se bonds on flavone structures using convenient Se powder via C-H functionalization is reported, regioselectively affording ArSe-substituted flavone derivatives in good yields.
