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2018 Volume 38 Issue 11
2018, 38(11): 2807-2832
doi: 10.6023/cjoc201805031
Abstract:
Oxime organic dyes, acting as photoredox catalysts, are widely used in visible-light-induced organic synthesis due to their advantages of low cost, good water solubility, high reactivity and so on. The type of organic dyes-catalyzed organic reactions is continuously expanding, and there is a tendency that organic dyes are gradually replacing some of transition metal catalysts. Classified by the type of reactions, the research progress of several common organic dyes in visible-light-induced organic synthesis in recent years is reviewed, and their future outlook is also discussed.
Oxime organic dyes, acting as photoredox catalysts, are widely used in visible-light-induced organic synthesis due to their advantages of low cost, good water solubility, high reactivity and so on. The type of organic dyes-catalyzed organic reactions is continuously expanding, and there is a tendency that organic dyes are gradually replacing some of transition metal catalysts. Classified by the type of reactions, the research progress of several common organic dyes in visible-light-induced organic synthesis in recent years is reviewed, and their future outlook is also discussed.
Recent Advances in the Synthesis of Heterocyclic Compounds via Pd-Catalyzed C(sp3)—H Bond Activation
2018, 38(11): 2833-2857
doi: 10.6023/cjoc201805028
Abstract:
Heterocyclic compounds are not only important intermediates in organic synthesis and medicine synthesis, but also the basic building framework of biologically active natural products. In recent years, Pd-catalyzed C(sp3)—H bonds activation has been demonstrated as one of the hot topics in the field of heterocyclic compound synthesis because of its high atomic economic characteristics. Herein, the recent research progress in the construction of heterocyclic compounds via Pd-catalyzed C(sp3)—H bond activation is summarized according to the classification of the ring number of heterocyclic compounds (mainly including N, O heterocycles). The reaction selectivity, substrate compatibility, reaction mechanism, advantages and disadvantages as well as an outlook in this field are also discussed.
Heterocyclic compounds are not only important intermediates in organic synthesis and medicine synthesis, but also the basic building framework of biologically active natural products. In recent years, Pd-catalyzed C(sp3)—H bonds activation has been demonstrated as one of the hot topics in the field of heterocyclic compound synthesis because of its high atomic economic characteristics. Herein, the recent research progress in the construction of heterocyclic compounds via Pd-catalyzed C(sp3)—H bond activation is summarized according to the classification of the ring number of heterocyclic compounds (mainly including N, O heterocycles). The reaction selectivity, substrate compatibility, reaction mechanism, advantages and disadvantages as well as an outlook in this field are also discussed.
2018, 38(11): 2858-2865
doi: 10.6023/cjoc201805061
Abstract:
Ketones are ubiquitous chemical entries in natural products, biologically active molecules, and functional materials. As such, developing operationally simple and general methods for the synthesis of these scaffolds is highly desiable. Recently, oxidative radical addition to aldehydes has emerged as a highly efficient strategy for the direct access of ketones. The strategy features a formal 1, 2-hydrogen atom transfer of resulting alkoxy radicals, followed by single electron transfer oxidation and deprotonation to give various cyclic or acyclic ketones in promising yields with a broad substrate scope. Recent advances in this area, including both intramolecular and intermolecular versions, are discussed herein.
Ketones are ubiquitous chemical entries in natural products, biologically active molecules, and functional materials. As such, developing operationally simple and general methods for the synthesis of these scaffolds is highly desiable. Recently, oxidative radical addition to aldehydes has emerged as a highly efficient strategy for the direct access of ketones. The strategy features a formal 1, 2-hydrogen atom transfer of resulting alkoxy radicals, followed by single electron transfer oxidation and deprotonation to give various cyclic or acyclic ketones in promising yields with a broad substrate scope. Recent advances in this area, including both intramolecular and intermolecular versions, are discussed herein.
2018, 38(11): 2866-2878
doi: 10.6023/cjoc201805046
Abstract:
Pyrrolo[1, 2-a] quinoxalines are a kind of important nitrogen-containing heterocycles which are widely existed in the natural products and bio-active molecules. Therefore, the synthesis of such motifs, especially those with substituted pyrrolo[1, 2-a] quinoxalines, is of great significance in theory and reality. This review focuses on the research process towards the synthesis of pyrrolo[1, 2-a] quinoxalines and 4, 5-dihydropyrrolo[1, 2-a] quinoxalines, including the advantages and disadvantages as well as an outlook in this field.
Pyrrolo[1, 2-a] quinoxalines are a kind of important nitrogen-containing heterocycles which are widely existed in the natural products and bio-active molecules. Therefore, the synthesis of such motifs, especially those with substituted pyrrolo[1, 2-a] quinoxalines, is of great significance in theory and reality. This review focuses on the research process towards the synthesis of pyrrolo[1, 2-a] quinoxalines and 4, 5-dihydropyrrolo[1, 2-a] quinoxalines, including the advantages and disadvantages as well as an outlook in this field.
2018, 38(11): 2879-2887
doi: 10.6023/cjoc201805013
Abstract:
Transition-metal-catalyzed decarboxylative cross-coupling reactions have been well developed as efficient synthetic methods in organic synthesis. Herein the new application of silver-catalyzed decarboxylation in Hunsdiecker-type halogenation, carbon-carbon bond formation, carbon-heteratom bond formation and C-H bond functionalization reaction is discussed. The recent progress in silver-catalyzed decarboxylative coupling reaction with aliphatic carboxylic acids, α-keto acids and aryl carboxylic acid is reviewed. With the assistance of peroxides, selective decarboxylative coupling reaction could be proceeded via free-radical process by silver catalysis. The controlled free-radical transformation is operational simplification without the exclusion of water and oxygen under mild conditions.
Transition-metal-catalyzed decarboxylative cross-coupling reactions have been well developed as efficient synthetic methods in organic synthesis. Herein the new application of silver-catalyzed decarboxylation in Hunsdiecker-type halogenation, carbon-carbon bond formation, carbon-heteratom bond formation and C-H bond functionalization reaction is discussed. The recent progress in silver-catalyzed decarboxylative coupling reaction with aliphatic carboxylic acids, α-keto acids and aryl carboxylic acid is reviewed. With the assistance of peroxides, selective decarboxylative coupling reaction could be proceeded via free-radical process by silver catalysis. The controlled free-radical transformation is operational simplification without the exclusion of water and oxygen under mild conditions.
2018, 38(11): 2888-2895
doi: 10.6023/cjoc201805049
Abstract:
Germanium-containing conjugated compounds are regarded as powerful candidates for the development of optoelectronic material. As a subclass of germanium-containing conjugated compounds and a crucial type of the heavy analogues of aromatic compounds, germanium-containing aromatic hydrocarbons (Ge-AHs) have attracted much attention and developed rapidly in recent days. According to the charge of the Ge-AHs, these species were categorized into three subclasses:neutral, anionic and cationic species. Herein, the synthetic methodology together with the reactivity of these reported Ge-AHs is summarized and the parameters used for the evaluation of the aromaticity of these compounds is highlighted. Ge-AHs and aromatic hydrocarbons share similar structural and magnetic properties. However, their major reactivity is quite different. This review will not only inspire the discovery of new structures and reactivities of Ge-Ahs, but also help to form a deeper understanding of the concept of aromaticy.
Germanium-containing conjugated compounds are regarded as powerful candidates for the development of optoelectronic material. As a subclass of germanium-containing conjugated compounds and a crucial type of the heavy analogues of aromatic compounds, germanium-containing aromatic hydrocarbons (Ge-AHs) have attracted much attention and developed rapidly in recent days. According to the charge of the Ge-AHs, these species were categorized into three subclasses:neutral, anionic and cationic species. Herein, the synthetic methodology together with the reactivity of these reported Ge-AHs is summarized and the parameters used for the evaluation of the aromaticity of these compounds is highlighted. Ge-AHs and aromatic hydrocarbons share similar structural and magnetic properties. However, their major reactivity is quite different. This review will not only inspire the discovery of new structures and reactivities of Ge-Ahs, but also help to form a deeper understanding of the concept of aromaticy.
2018, 38(11): 2896-2926
doi: 10.6023/cjoc201804027
Abstract:
Organic boronic reagents have played a critical role in the field of organic synthesis, especially Suzuki coupling, since they were founded. In return, all kinds of transition metal (Pd, Ni, Rh, Au etc.)-catalyzed coupling reactions have given a big push for the development and application of organic boronic reagents. 2, 4, 6-Mesitylboronic acid was used widely in various coupling reactions, including Suzuiki reaction, aromatic C-H activation, oxidative Heck reaction, carbonlation, decarboxylation, photoredox reaction and other C-X (C-N, C-S, C-Se) bonding reaction, which was used to synthesize functional materials, ligands and drug molecules. This paper includes two aspects:(1) reviewing the application of mesityl boronic acid and its ester in coupling reaction, and (2) making our points and respecting for this field.
Organic boronic reagents have played a critical role in the field of organic synthesis, especially Suzuki coupling, since they were founded. In return, all kinds of transition metal (Pd, Ni, Rh, Au etc.)-catalyzed coupling reactions have given a big push for the development and application of organic boronic reagents. 2, 4, 6-Mesitylboronic acid was used widely in various coupling reactions, including Suzuiki reaction, aromatic C-H activation, oxidative Heck reaction, carbonlation, decarboxylation, photoredox reaction and other C-X (C-N, C-S, C-Se) bonding reaction, which was used to synthesize functional materials, ligands and drug molecules. This paper includes two aspects:(1) reviewing the application of mesityl boronic acid and its ester in coupling reaction, and (2) making our points and respecting for this field.
2018, 38(11): 2927-2936
doi: 10.6023/cjoc201805042
Abstract:
Chiral compounds play an essential role in asymmetric synthesis, biology, medical field and pharmacology. It is necessary to establish fast, sensitive and high enantioselective chiral analysis methods. Chiral sensors, which could determine the absolute configuration and the value of enantiomeric excess of enantiomers, have the advantages of simple, rapid, sensitive and real-time. Herein, the review is focused on the recent progress of chiral fluorescent sensors, circular dichroism sensors, UV-Vis sensors, NMR sensors and MS sensors. Their characteristics, sensing mechanism and applications in chiral recognition are reviewed, and the prospects of chiral sensors are also discussed.
Chiral compounds play an essential role in asymmetric synthesis, biology, medical field and pharmacology. It is necessary to establish fast, sensitive and high enantioselective chiral analysis methods. Chiral sensors, which could determine the absolute configuration and the value of enantiomeric excess of enantiomers, have the advantages of simple, rapid, sensitive and real-time. Herein, the review is focused on the recent progress of chiral fluorescent sensors, circular dichroism sensors, UV-Vis sensors, NMR sensors and MS sensors. Their characteristics, sensing mechanism and applications in chiral recognition are reviewed, and the prospects of chiral sensors are also discussed.
2018, 38(11): 2937-2992
doi: 10.6023/cjoc201803047
Abstract:
While the metallocene catalysts were widely used to produce the metallocene polypropylenes (mPP) in other countries, the traditional Ziegler-Natta catalyst has still been dominantly employed for manufacturing the polypropylenes (PP) in our country at current time. The property of the mPP appears more improved than that of the PP produced by the Ziegler-Natta catalyst, and the market demand for the mPP is worldwidely increasing every year. Therefore, it is urgent to develop the metallocene catalysts for the industrial use in domestic companies. The metallocene catalysts are of versatile structures, which are able to show more exact control over the propylene polymerization activity and the polypropylene stereostructures than the Ziegler-Natta catalyst, and thus catalyze to generate new PPs of the diverse structures. This manuscript will give a detailed summary on the metallocene catalysts so far reported. The important factors such as temperature, propylene pressure, catalyst concentration, cocatalyst types and so on will be illustrated, which all have significant influence on the catalytic reaction activity. The reaction mechanism will be discussed as well.
While the metallocene catalysts were widely used to produce the metallocene polypropylenes (mPP) in other countries, the traditional Ziegler-Natta catalyst has still been dominantly employed for manufacturing the polypropylenes (PP) in our country at current time. The property of the mPP appears more improved than that of the PP produced by the Ziegler-Natta catalyst, and the market demand for the mPP is worldwidely increasing every year. Therefore, it is urgent to develop the metallocene catalysts for the industrial use in domestic companies. The metallocene catalysts are of versatile structures, which are able to show more exact control over the propylene polymerization activity and the polypropylene stereostructures than the Ziegler-Natta catalyst, and thus catalyze to generate new PPs of the diverse structures. This manuscript will give a detailed summary on the metallocene catalysts so far reported. The important factors such as temperature, propylene pressure, catalyst concentration, cocatalyst types and so on will be illustrated, which all have significant influence on the catalytic reaction activity. The reaction mechanism will be discussed as well.
2018, 38(11): 2993-3001
doi: 10.6023/cjoc201804048
Abstract:
Pyropheophorbide-a methyl ester and its derivatives acidylated and alkenylated along the N21-N23 axis were used as starting materials. The 1, 3-dipolar cyclocaddition, Michael addition and Tiffeneau-Demjanov rearrangement reaction can smoothly occur with diazoalkane through the carbon-oxygen or carbon-carbon double bonds attached to the periphery to generate new heterocyclic and carbonylic structures in different positions. The synthesis of a series of unreported chlorins related to chlorophyll was accomplished and their chemical structures were characterized by elemental analysis, UV-Vis, IR, MS and 1H NMR spectra. Meanwhile, the region-and stereo-selectivities of rearrangement processes were discussed based on relevant reaction mechanism.
Pyropheophorbide-a methyl ester and its derivatives acidylated and alkenylated along the N21-N23 axis were used as starting materials. The 1, 3-dipolar cyclocaddition, Michael addition and Tiffeneau-Demjanov rearrangement reaction can smoothly occur with diazoalkane through the carbon-oxygen or carbon-carbon double bonds attached to the periphery to generate new heterocyclic and carbonylic structures in different positions. The synthesis of a series of unreported chlorins related to chlorophyll was accomplished and their chemical structures were characterized by elemental analysis, UV-Vis, IR, MS and 1H NMR spectra. Meanwhile, the region-and stereo-selectivities of rearrangement processes were discussed based on relevant reaction mechanism.
2018, 38(11): 3009-3015
doi: 10.6023/cjoc201806035
Abstract:
Isobenzofuranone derivatives are widely found in nature and have shown diverse biological activities. In this work, the aniline-promoted synthesis of isobenzofuranone derivatives starting from 2-carboxybenzaldehyde and substituted acetophenones under mild reaction conditions is reported. This method has broad substrate scope, high yields, and is operationally convenient, and therefore could serve as an attractive strategy for practical synthesis of isobenzofuranone derivatives.
Isobenzofuranone derivatives are widely found in nature and have shown diverse biological activities. In this work, the aniline-promoted synthesis of isobenzofuranone derivatives starting from 2-carboxybenzaldehyde and substituted acetophenones under mild reaction conditions is reported. This method has broad substrate scope, high yields, and is operationally convenient, and therefore could serve as an attractive strategy for practical synthesis of isobenzofuranone derivatives.
2018, 38(11): 3016-3025
doi: 10.6023/cjoc201805038
Abstract:
Quinoline derivatives, aryl hydrazines and hydrazide compounds have significant biological activities. Benzo[h] quinoline derivatives were synthesized from 1-naphthylamine, substituted benzaldehyde and methyl pyruvate by Doebner-Miller reaction. After the ester was reduced, the corresponding aldehyde was obtained by oxidation. Benzo[h] quinolinium and quinoline hydrazide compounds were synthesized by reacting benzo[h] quinoline formaldehyde with hydrazine salts and hydrazides, respectively. The preliminary activity data showed that most of the compounds exhibited significant inhibitory activities against cycle protein 25B (CDC 25B) and protein tyrosine phosphatase PTP 1B.
Quinoline derivatives, aryl hydrazines and hydrazide compounds have significant biological activities. Benzo[h] quinoline derivatives were synthesized from 1-naphthylamine, substituted benzaldehyde and methyl pyruvate by Doebner-Miller reaction. After the ester was reduced, the corresponding aldehyde was obtained by oxidation. Benzo[h] quinolinium and quinoline hydrazide compounds were synthesized by reacting benzo[h] quinoline formaldehyde with hydrazine salts and hydrazides, respectively. The preliminary activity data showed that most of the compounds exhibited significant inhibitory activities against cycle protein 25B (CDC 25B) and protein tyrosine phosphatase PTP 1B.
2018, 38(11): 3026-3031
doi: 10.6023/cjoc201804041
Abstract:
A novel carbazole-based Schiff base derivative L was synthesized and evaluated for the property of selective detection of HSO4- ion in aqueous medium. N-(9-Ethyl-carbazol-3-yl)-1-methyl-1-(4-nitrophenyl)-methanimine (L) selectively recognized HSO4- ion in CH3CN-H2O (V:V=9:1) via the hydrolysis reaction of Schiff bases to elicit a distinct visual colour change from orange to colorless with a significant blue fluorescence under the UV lamp. The fluorescence enhancement phenomenon caused by HSO4- ion did not change in the presence of other anions. The sensing mechanism of probe L for HSO4- had been investigated by Job's plot, 1H NMR titration spectra and HRMS spectrum. The detection limit for the HSO4- ion was determined as 1.91×10-8mol·L-1. The compound L can be used as a highly selective and sensitive colorimetric, and fluorescent turn-on probe for HSO4-.
A novel carbazole-based Schiff base derivative L was synthesized and evaluated for the property of selective detection of HSO4- ion in aqueous medium. N-(9-Ethyl-carbazol-3-yl)-1-methyl-1-(4-nitrophenyl)-methanimine (L) selectively recognized HSO4- ion in CH3CN-H2O (V:V=9:1) via the hydrolysis reaction of Schiff bases to elicit a distinct visual colour change from orange to colorless with a significant blue fluorescence under the UV lamp. The fluorescence enhancement phenomenon caused by HSO4- ion did not change in the presence of other anions. The sensing mechanism of probe L for HSO4- had been investigated by Job's plot, 1H NMR titration spectra and HRMS spectrum. The detection limit for the HSO4- ion was determined as 1.91×10-8mol·L-1. The compound L can be used as a highly selective and sensitive colorimetric, and fluorescent turn-on probe for HSO4-.
2018, 38(11): 3032-3038
doi: 10.6023/cjoc201803025
Abstract:
An efficient method for carbon-carbon bond formation via desulfurative coupling of pyrimidine thioethers/4-phenylquinoline thioethers with alkynes or arylboronic acids is described. The reaction was promoted by a cheap and stable copper salt[copper(I) acetate] and catalyzed by palladium with good yields and wild substrate scope.
An efficient method for carbon-carbon bond formation via desulfurative coupling of pyrimidine thioethers/4-phenylquinoline thioethers with alkynes or arylboronic acids is described. The reaction was promoted by a cheap and stable copper salt[copper(I) acetate] and catalyzed by palladium with good yields and wild substrate scope.
2018, 38(11): 3063-3069
doi: 10.6023/cjoc201805015
Abstract:
In order to find the efficient and novel antitumor drugs, a series of 2-methylthio-4-arylamine quinazoline derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines initially including MGC-803, PC-3, HGC-27 and A549. The results showed that some compounds had good antitumor activities, especially N-(4-fluorophenyl)-2-(methylthio) quinazolin-4-amine (9c) and 2-(methylthio)-N-(p-tolyl)-quina-zolin-4-amine (9m), with IC50 values of 0.18 and 0.68 μmol·L-1, respectively.
In order to find the efficient and novel antitumor drugs, a series of 2-methylthio-4-arylamine quinazoline derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines initially including MGC-803, PC-3, HGC-27 and A549. The results showed that some compounds had good antitumor activities, especially N-(4-fluorophenyl)-2-(methylthio) quinazolin-4-amine (9c) and 2-(methylthio)-N-(p-tolyl)-quina-zolin-4-amine (9m), with IC50 values of 0.18 and 0.68 μmol·L-1, respectively.
2018, 38(11): 3070-3077
doi: 10.6023/cjoc201805034
Abstract:
Oxidative kinetics resolution of racemic aromatic sulfoxide was studied by using chiral porphyrin-inspired N4 ligands and manganese in situ complex as catalyst, environment-friendly H2O2 as oxidant and adamantanecarboxylic acid as additive. The arylalkyl and arylbenzyl sulfoxide substrates were extended by this catalytic system. A maximum yield of chiral sulfoxide was 40% and the enantioselectivity was 100%. In the meantime, the yield of sulfone a further oxidation products of sulfoxide, was up to 72%. It was found that the catalytic oxidation system is more prone to electron-rich sulfoxide through the competition experiment between electron-rich sulfoxide and electron-deficient sulfoxide substrates. In addition, the success of gram-scale oxidation kinetic resolution also shows that this method has a certain practical value in methodology.
Oxidative kinetics resolution of racemic aromatic sulfoxide was studied by using chiral porphyrin-inspired N4 ligands and manganese in situ complex as catalyst, environment-friendly H2O2 as oxidant and adamantanecarboxylic acid as additive. The arylalkyl and arylbenzyl sulfoxide substrates were extended by this catalytic system. A maximum yield of chiral sulfoxide was 40% and the enantioselectivity was 100%. In the meantime, the yield of sulfone a further oxidation products of sulfoxide, was up to 72%. It was found that the catalytic oxidation system is more prone to electron-rich sulfoxide through the competition experiment between electron-rich sulfoxide and electron-deficient sulfoxide substrates. In addition, the success of gram-scale oxidation kinetic resolution also shows that this method has a certain practical value in methodology.
2018, 38(11): 3086-3093
doi: 10.6023/cjoc201805020
Abstract:
The structure modification and optimization focused on the N-phenylpyrazole motif of the lead compound 2 were conducted on basis of the structural features of focal adhesion kinase (FAK) allosteric hydrophobic pockets. Nine aimed compounds were designed and synthesized, among which four compounds maintained the inhibitory activity against FAK at the same level as 2. Especially, N-(4-(5-(3-(4-(6-amino-9H-purin-9-yl) phenyl) ureido)-3-(tert-butyl)-1H-pyrazol-1-yl) phenyl) ace-tamide (9e) demonstrated 2-fold higher inhibition potency than that of the lead compound with the IC50 value of 41 nmol/L. It is suggested that the bioactivity could be further improved by introducing more proper groups at the 4-position of phenyl to increase the interactions between the substituents and the residues around them.
The structure modification and optimization focused on the N-phenylpyrazole motif of the lead compound 2 were conducted on basis of the structural features of focal adhesion kinase (FAK) allosteric hydrophobic pockets. Nine aimed compounds were designed and synthesized, among which four compounds maintained the inhibitory activity against FAK at the same level as 2. Especially, N-(4-(5-(3-(4-(6-amino-9H-purin-9-yl) phenyl) ureido)-3-(tert-butyl)-1H-pyrazol-1-yl) phenyl) ace-tamide (9e) demonstrated 2-fold higher inhibition potency than that of the lead compound with the IC50 value of 41 nmol/L. It is suggested that the bioactivity could be further improved by introducing more proper groups at the 4-position of phenyl to increase the interactions between the substituents and the residues around them.
2018, 38(11): 3002-3008
doi: 10.6023/cjoc201803038
Abstract:
L-Cys-β-CD@AuNPs nanoparticles were synthesized by a simple method of the reduction of HAuCl4 with NaBH4and L-Cys-CD. The catalytic activity of L-Cys-β-CD@AuNPs nanoparticles for the catalytic reductions of 4-nitrophenol and 4-nitro-1-naphthol was researched in detail. Because of the selective binding of β-cyclodextrin (β-CD) to different guest molecules, L-Cys-β-CD@AuNPs exhibits diverse catalytic activities for different substrates. The experimental results prove that L-Cys-β-CD@AuNPs shows better catalytic efficiency for the reduction of 4-nitro-1-naphthol than p-nitrophenol.
L-Cys-β-CD@AuNPs nanoparticles were synthesized by a simple method of the reduction of HAuCl4 with NaBH4and L-Cys-CD. The catalytic activity of L-Cys-β-CD@AuNPs nanoparticles for the catalytic reductions of 4-nitrophenol and 4-nitro-1-naphthol was researched in detail. Because of the selective binding of β-cyclodextrin (β-CD) to different guest molecules, L-Cys-β-CD@AuNPs exhibits diverse catalytic activities for different substrates. The experimental results prove that L-Cys-β-CD@AuNPs shows better catalytic efficiency for the reduction of 4-nitro-1-naphthol than p-nitrophenol.
2018, 38(11): 3039-3047
doi: 10.6023/cjoc201805035
Abstract:
A series of natural product-like terphenyls were synthesized, and their biological activities were evaluated. 4″-Amino-[1, 1':4', 1″-terphenyl]-3, 4-diol (17) has the most potent cytotoxic activity against the MDA-MB-435 cell line, and the IC50 value is (0.20±1.12) μmol/L, which is more potent than compounds X1 and X2 obtained in our previous studies. DNA relaxation test showed that compound 17 had a strong inhibitory effect on topoisomerase Ⅱα (TOP2α), but not on topoisomerase Ⅰ (TOP1), which was consistent with the docking analysis results. Our studies demonstrate that N contained substitutes on ring C are important for producing terphenyls with more efficacious activity against TOP2α, which provide insight into the development of novel terphenyl topoisomerase Ⅱα inhibitors.
A series of natural product-like terphenyls were synthesized, and their biological activities were evaluated. 4″-Amino-[1, 1':4', 1″-terphenyl]-3, 4-diol (17) has the most potent cytotoxic activity against the MDA-MB-435 cell line, and the IC50 value is (0.20±1.12) μmol/L, which is more potent than compounds X1 and X2 obtained in our previous studies. DNA relaxation test showed that compound 17 had a strong inhibitory effect on topoisomerase Ⅱα (TOP2α), but not on topoisomerase Ⅰ (TOP1), which was consistent with the docking analysis results. Our studies demonstrate that N contained substitutes on ring C are important for producing terphenyls with more efficacious activity against TOP2α, which provide insight into the development of novel terphenyl topoisomerase Ⅱα inhibitors.
2018, 38(11): 3048-3055
doi: 10.6023/cjoc201805009
Abstract:
A selective Hay coupling reaction of aromatic terminal acetylenes and monophosphoryl-protected diynes was developed. The polarity of Ph2P(O) realized facile isolation of the desired unsymmetrical 1, 3-diynes from by-products. The low reactivity of monophosphoryl-protected diynes reduced the oxidative homocoupling of itself and enhanced the yields of desired products. A number of aromatic terminal acetylenes and monophosphoryl-protected diynes were tolerated in this reaction, and all the corresponding unsymmetrical 1, 3-diynes could be obtained in moderate to good yields. The unsymmetrical 1, 3-diynes could be applied to synthesize unsymmetrical yne-diynes and cyclic polyynes.
A selective Hay coupling reaction of aromatic terminal acetylenes and monophosphoryl-protected diynes was developed. The polarity of Ph2P(O) realized facile isolation of the desired unsymmetrical 1, 3-diynes from by-products. The low reactivity of monophosphoryl-protected diynes reduced the oxidative homocoupling of itself and enhanced the yields of desired products. A number of aromatic terminal acetylenes and monophosphoryl-protected diynes were tolerated in this reaction, and all the corresponding unsymmetrical 1, 3-diynes could be obtained in moderate to good yields. The unsymmetrical 1, 3-diynes could be applied to synthesize unsymmetrical yne-diynes and cyclic polyynes.
2018, 38(11): 3056-3062
doi: 10.6023/cjoc201803040
Abstract:
An efficient N-heterocyclic carbene-catalyzed oxidative esterification reaction of aldehydes with ethyl bromoacetate or bromoacetonitrile has been explored. This transition metal-free protocol allows access to a wide variety of α-acyloxyacetates and cyanomethyl esters in good to excellent yields under mild reaction condition.
An efficient N-heterocyclic carbene-catalyzed oxidative esterification reaction of aldehydes with ethyl bromoacetate or bromoacetonitrile has been explored. This transition metal-free protocol allows access to a wide variety of α-acyloxyacetates and cyanomethyl esters in good to excellent yields under mild reaction condition.
2018, 38(11): 3078-3085
doi: 10.6023/cjoc201805018
Abstract:
Palladium catalyzed cross-coupling of 3, 6-(Bpin)2-o-carborane (Bpin=pinacolatoboryl) with aryl bromides has been achieved, leading to the formation of a series of B(3, 6)-diarylated-o-carborane derivatives in moderate yields. In this reaction, PdCl2(cod)/tricyclohexylphosphine was used as catalyst to avoid the formation of palladium-catalyzed aryl-aryl exchange and direct B-H arylation by-products. A possible mechanism is proposed, involving a tandem sequence of oxidative addition, anion exchange, transmetalation, and reductive elimination.
Palladium catalyzed cross-coupling of 3, 6-(Bpin)2-o-carborane (Bpin=pinacolatoboryl) with aryl bromides has been achieved, leading to the formation of a series of B(3, 6)-diarylated-o-carborane derivatives in moderate yields. In this reaction, PdCl2(cod)/tricyclohexylphosphine was used as catalyst to avoid the formation of palladium-catalyzed aryl-aryl exchange and direct B-H arylation by-products. A possible mechanism is proposed, involving a tandem sequence of oxidative addition, anion exchange, transmetalation, and reductive elimination.
2018, 38(11): 3094-3100
doi: 10.6023/cjoc201807047
Abstract:
A pharmaceutical intermediate, 3-pyridyl benzoxazole derivatives (DIHY), was designed and synthesized as the guest molecule. The self-assembly binding models of tetramethyl cucurbit[6] uril (TMeQ[6]), cucurbit[7] uril (Q[7]) and cucurbit[8] uril (Q[8]) with DIHY were investigated by 1H NMR, MS, isothermal titration calorimetry and UV-Vis spectrum. The results showed that there are different modes of interaction between these three different cucurbit[n] uril and DIHY. For the TMeQ[6]-DIHY system, the guest molecule is located at the port of the TMeQ[6], while for the Q[7]-DIHY system, the 4, 5-dihydro-2H-benzoxazole moiety of the guest molecule reside within the cavity of Q[7] host, whereas the pyridyl group of DIHY guest remains outside of the portal to form the 1:1 inclusion complexes of pseudorotaxane structure. Nevertheless, the 4, 5-dihydro-2H-benzoxazole moiety of two guest molecule is included in the cavity of Q[8] host in a "face to face" stacking way, while the pyridine group of DIHY is located at the port of Q[8] to form a 1:2 supramolecular structure.
A pharmaceutical intermediate, 3-pyridyl benzoxazole derivatives (DIHY), was designed and synthesized as the guest molecule. The self-assembly binding models of tetramethyl cucurbit[6] uril (TMeQ[6]), cucurbit[7] uril (Q[7]) and cucurbit[8] uril (Q[8]) with DIHY were investigated by 1H NMR, MS, isothermal titration calorimetry and UV-Vis spectrum. The results showed that there are different modes of interaction between these three different cucurbit[n] uril and DIHY. For the TMeQ[6]-DIHY system, the guest molecule is located at the port of the TMeQ[6], while for the Q[7]-DIHY system, the 4, 5-dihydro-2H-benzoxazole moiety of the guest molecule reside within the cavity of Q[7] host, whereas the pyridyl group of DIHY guest remains outside of the portal to form the 1:1 inclusion complexes of pseudorotaxane structure. Nevertheless, the 4, 5-dihydro-2H-benzoxazole moiety of two guest molecule is included in the cavity of Q[8] host in a "face to face" stacking way, while the pyridine group of DIHY is located at the port of Q[8] to form a 1:2 supramolecular structure.
2018, 38(11): 3101-3105
doi: 10.6023/cjoc201804049
Abstract:
In the presence of copper acetate, ten 5-(1-phenyl-3-phenylprop-2-ynyl)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione derivatives were synthesized via the three component one-pot reaction of aldehydes with 2, 2-dimethyl-1, 3-dioxane-4, 6-dione and phenylacetylene by using Na-ascorbate as a reductant. The reaction has the advantages of high yields (65%~86%), mild conditions, simple operation and environmental friendliness. It provides an effective method for the synthesis of 5-(1-phenyl-3-phenylprop-2-ynyl)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione derivatives.
In the presence of copper acetate, ten 5-(1-phenyl-3-phenylprop-2-ynyl)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione derivatives were synthesized via the three component one-pot reaction of aldehydes with 2, 2-dimethyl-1, 3-dioxane-4, 6-dione and phenylacetylene by using Na-ascorbate as a reductant. The reaction has the advantages of high yields (65%~86%), mild conditions, simple operation and environmental friendliness. It provides an effective method for the synthesis of 5-(1-phenyl-3-phenylprop-2-ynyl)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione derivatives.
2018, 38(11): 3112-3117
doi: 10.6023/cjoc201804044
Abstract:
In order to find novel biologically active heterocyclic compounds, thirteen new 2-(substitutedbenzylthio)-5-(4, 6-dimethylpyrimidin-2-thiomethyl)-1, 3, 4-oxadiazoles were prepared with thiocarbamide and 2, 4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and finally a benzylation reaction under microwave irradiation condition. The preliminary bioassay results indicated that some target compounds exhibited good inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of the compound with 3-fluoro against Colletrotichum acutatum reached 80.22%. Several compounds also showed that good antileishmanial activities against Leishmania donovani, the IC50 values of those compounds with 3-chloro, 4-bromo, 3-fluoro and 4-tert-butyl substituent respectively were all less than 25 μg/mL and were more active than the control drug paromomycin.
In order to find novel biologically active heterocyclic compounds, thirteen new 2-(substitutedbenzylthio)-5-(4, 6-dimethylpyrimidin-2-thiomethyl)-1, 3, 4-oxadiazoles were prepared with thiocarbamide and 2, 4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and finally a benzylation reaction under microwave irradiation condition. The preliminary bioassay results indicated that some target compounds exhibited good inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of the compound with 3-fluoro against Colletrotichum acutatum reached 80.22%. Several compounds also showed that good antileishmanial activities against Leishmania donovani, the IC50 values of those compounds with 3-chloro, 4-bromo, 3-fluoro and 4-tert-butyl substituent respectively were all less than 25 μg/mL and were more active than the control drug paromomycin.
2018, 38(11): 3123-3126
doi: 10.6023/cjoc201804037
Abstract:
2-(1H-Benzo[d] imidazol-2-yl)-3-arylacrylonitrile derivatives not only exhibit a variety of important biological activities, but also are important intermediates in organic synthesis. The CBr4-promoted reaction of aromatic aldehydes with 2-(1H-benzo[d] imidazol-2-yl) acetonitrile to obtain 2-(1H-benzo[d] imidazol-2-yl)-3-arylacrylonitriles was developed. Structurally diverse 2-(1H-benzo[d] imidazol-2-yl)-3-arylacrylonitriles were obtained in moderate to good yields (74%~96%) under mild conditions. This method has the advantages of operational simplicity and wide substrate scope.
2-(1H-Benzo[d] imidazol-2-yl)-3-arylacrylonitrile derivatives not only exhibit a variety of important biological activities, but also are important intermediates in organic synthesis. The CBr4-promoted reaction of aromatic aldehydes with 2-(1H-benzo[d] imidazol-2-yl) acetonitrile to obtain 2-(1H-benzo[d] imidazol-2-yl)-3-arylacrylonitriles was developed. Structurally diverse 2-(1H-benzo[d] imidazol-2-yl)-3-arylacrylonitriles were obtained in moderate to good yields (74%~96%) under mild conditions. This method has the advantages of operational simplicity and wide substrate scope.
2018, 38(11): 3127-3136
doi: 10.6023/cjoc201806027
Abstract:
A polyimide-urethane reverse osmosis (RO) composite membrane (MMPD-CFIC@CFIC-DMMPD) was prepared through the reaction of N, N'-dimethyl-m-phenylenediamine (DMMPD) and 4-methyl-phenylenediamine (MMPD) with 5-choroformyloxyisophaloyl chloride (CFIC) via two-step interfacial polymerization method, and this membrane exhibits good oxidation resistance. Then, this MMPD-CFIC@CFIC-DMMPD membrane was further modified with NaA zeolite by doping in the CFIC organic phase. The chemical structure of membrane active layer was examined by the attenuated total reflectance infrared (ATR-IR) and X-ray photoelectronic spectroscopy (XPS). The membrane surface and cross-section morphologies were observed with scanning electronic microscopy (SEM), atomic force microscope (AFM) and transmission electron microscopy (TEM), and the hydrophicity of membrane surface was evaluated by contact angle. Moreover, the separation performance, chlorine resistance and organic foulant resistance properties of the two membranes were systematically investigated. The results showed that the modified polyimide-urethane RO membrane (MMPD-CFIC/NaA@CFIC-DMMPD) presented higher water flux, better organic foulant resistance performance as well as favourite chlorine resistance property than the origin MMPD-CFIC@CFIC-DMMPD membrane due to the incorporating of NaA nanoparticles into the membrane.
A polyimide-urethane reverse osmosis (RO) composite membrane (MMPD-CFIC@CFIC-DMMPD) was prepared through the reaction of N, N'-dimethyl-m-phenylenediamine (DMMPD) and 4-methyl-phenylenediamine (MMPD) with 5-choroformyloxyisophaloyl chloride (CFIC) via two-step interfacial polymerization method, and this membrane exhibits good oxidation resistance. Then, this MMPD-CFIC@CFIC-DMMPD membrane was further modified with NaA zeolite by doping in the CFIC organic phase. The chemical structure of membrane active layer was examined by the attenuated total reflectance infrared (ATR-IR) and X-ray photoelectronic spectroscopy (XPS). The membrane surface and cross-section morphologies were observed with scanning electronic microscopy (SEM), atomic force microscope (AFM) and transmission electron microscopy (TEM), and the hydrophicity of membrane surface was evaluated by contact angle. Moreover, the separation performance, chlorine resistance and organic foulant resistance properties of the two membranes were systematically investigated. The results showed that the modified polyimide-urethane RO membrane (MMPD-CFIC/NaA@CFIC-DMMPD) presented higher water flux, better organic foulant resistance performance as well as favourite chlorine resistance property than the origin MMPD-CFIC@CFIC-DMMPD membrane due to the incorporating of NaA nanoparticles into the membrane.
2018, 38(11): 3137-3140
doi: 10.6023/cjoc201804028
Abstract:
A new stemodane diterpenoid, trigoheterone A (1), together with seven known diterpenoids, was isolated from the stems and leaves of Trigonostemon heterophyllus. Their structures were established on the basis of extensive spectral analyses. All known compounds were isolated from the genus Trigonostemon for the first time. The cytotoxicities of all isolated compounds were evaluated against five cancer cell lines (HL-60, A549, SMMC-7721, MCF-7 and SW480). As a result, eight compounds exhibited significant inhibitory effects with IC50 values comparable to those of cisplatin.
A new stemodane diterpenoid, trigoheterone A (1), together with seven known diterpenoids, was isolated from the stems and leaves of Trigonostemon heterophyllus. Their structures were established on the basis of extensive spectral analyses. All known compounds were isolated from the genus Trigonostemon for the first time. The cytotoxicities of all isolated compounds were evaluated against five cancer cell lines (HL-60, A549, SMMC-7721, MCF-7 and SW480). As a result, eight compounds exhibited significant inhibitory effects with IC50 values comparable to those of cisplatin.
2018, 38(11): 3106-3111
doi: 10.6023/cjoc201803027
Abstract:
In this study, a controlled synthesis of hyper-crosslinked monodisperse microsphere with homogeneous mesoporous aperture about 6 nm is presented. After supported with palladium, the catalyst was performed by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption and desorption surface area analyses. The results showed that HCP-(PS-DVB)-Pd(0) possessed high catalytic activity for Suzuki-Miyaura cross-coupling reaction at room temperature, and the catalyst also show excellent reusability. After recycled for 10 times, the yield can maintain above 95% and the surface areas can still reach 480.5 m2·g-1. These results suggest that the HCP-(PS-DVB)-Pd(0) catalyst has potential applications in synthetic and industrial chemistry.
In this study, a controlled synthesis of hyper-crosslinked monodisperse microsphere with homogeneous mesoporous aperture about 6 nm is presented. After supported with palladium, the catalyst was performed by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption and desorption surface area analyses. The results showed that HCP-(PS-DVB)-Pd(0) possessed high catalytic activity for Suzuki-Miyaura cross-coupling reaction at room temperature, and the catalyst also show excellent reusability. After recycled for 10 times, the yield can maintain above 95% and the surface areas can still reach 480.5 m2·g-1. These results suggest that the HCP-(PS-DVB)-Pd(0) catalyst has potential applications in synthetic and industrial chemistry.
2018, 38(11): 3118-3122
doi: 10.6023/cjoc201804005
Abstract:
Ten gastrodine intermediate analogues were synthesized by the Knoevenagel reaction of 4-formylphenyl(2, 3, 4, 6-tetra-O-acetyl)-β-D-glucoside and 1, 3-dioxane-4, 6-dione with gluconic acid as a catalyst. In this reaction there are many advantages with good to excellent yields (78%~92%), mild conditions, simple operations and environmental friendliness. Additionally, gluconic acid could be recycled and reused many times without lossing its efficiency.
Ten gastrodine intermediate analogues were synthesized by the Knoevenagel reaction of 4-formylphenyl(2, 3, 4, 6-tetra-O-acetyl)-β-D-glucoside and 1, 3-dioxane-4, 6-dione with gluconic acid as a catalyst. In this reaction there are many advantages with good to excellent yields (78%~92%), mild conditions, simple operations and environmental friendliness. Additionally, gluconic acid could be recycled and reused many times without lossing its efficiency.
