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2017 Volume 37 Issue 7
2017, 37(7): 1589-1612
doi: 10.6023/cjoc201704017
Abstract:
Chiral amines are important building blocks in organic synthesis, they also present in numerous natural products, biologically active compounds and pharmaceutical agents. In recent years, the use of various organoboron reagents in transition metal-catalyzed reactions has attracted considerable attentions because of their ready avilibility, low toxicity, good air and moisture stability as well as high functional group compatibility. This review summarizes the remarkable progress and advances in transition metal-catalyzed asymmetric addition of organoboron reagents to imines over the past few years, providing an overview of the recent achievements in stereoselective synthesis of α-chiral amines by using chiral auxiliary or chiral catalysis strategies. At the present time, rhodium-based asymmetric catalysis has proven to be the most efficient and reliable approach to furnish highly optically active α-chiral amines. Varieties of chiral ligands including monophosphines, biphosphines, amidomonophosphanes, phosphoramidites, phosphites, dienes, sulfur-olefins, phosphorus-olefins have showed the great potential in many asymmetric additions of organoboron reagents to imines, enabling the access of both secondary and tertiary α-chiral amines with good to excellent enantioselectivities. On the other hand, important progress has been made in developing effective palladium catalysts mainly based on chiral pyridine-oxazoline and phosphine-oxazoline ligands. However, future studies in this area towards the objective of developing more efficient, practical and general methods remain challenging.
Chiral amines are important building blocks in organic synthesis, they also present in numerous natural products, biologically active compounds and pharmaceutical agents. In recent years, the use of various organoboron reagents in transition metal-catalyzed reactions has attracted considerable attentions because of their ready avilibility, low toxicity, good air and moisture stability as well as high functional group compatibility. This review summarizes the remarkable progress and advances in transition metal-catalyzed asymmetric addition of organoboron reagents to imines over the past few years, providing an overview of the recent achievements in stereoselective synthesis of α-chiral amines by using chiral auxiliary or chiral catalysis strategies. At the present time, rhodium-based asymmetric catalysis has proven to be the most efficient and reliable approach to furnish highly optically active α-chiral amines. Varieties of chiral ligands including monophosphines, biphosphines, amidomonophosphanes, phosphoramidites, phosphites, dienes, sulfur-olefins, phosphorus-olefins have showed the great potential in many asymmetric additions of organoboron reagents to imines, enabling the access of both secondary and tertiary α-chiral amines with good to excellent enantioselectivities. On the other hand, important progress has been made in developing effective palladium catalysts mainly based on chiral pyridine-oxazoline and phosphine-oxazoline ligands. However, future studies in this area towards the objective of developing more efficient, practical and general methods remain challenging.
2017, 37(7): 1613-1628
doi: 10.6023/cjoc201703020
Abstract:
8-Aminoquinolines are important nitrogen-containing heterocycles widely existing in the natural products, bio-active molecules and agrochemicals. It has been developed as significant bidentate directing groups or as ligand auxiliary in various kinds of organic reactions, especially in the area of C-H bond functionalization. Therefore, the synthesis of such motifs, especially those with substituted quinolines is of great significance. This review focuses on the remote C-H bond functionalizaitons of 8-aminoquinolines on the C(5) position, including the advantages and disadvantages as well as an outlook in this field.
8-Aminoquinolines are important nitrogen-containing heterocycles widely existing in the natural products, bio-active molecules and agrochemicals. It has been developed as significant bidentate directing groups or as ligand auxiliary in various kinds of organic reactions, especially in the area of C-H bond functionalization. Therefore, the synthesis of such motifs, especially those with substituted quinolines is of great significance. This review focuses on the remote C-H bond functionalizaitons of 8-aminoquinolines on the C(5) position, including the advantages and disadvantages as well as an outlook in this field.
2017, 37(7): 1629-1652
doi: 10.6023/cjoc201702048
Abstract:
The morphine alkaloids constitute a class of structurally related natural products isolated from opium poppy, Papaver somniferum. The synthesis of morphine and its derivatives has attracted the attention of many generations of synthetic chemists due to their highly challenging molecular architecture and biological activities. Progresses toward the synthesis of the morphine alkaloids are reviewed in terms of chronological order.
The morphine alkaloids constitute a class of structurally related natural products isolated from opium poppy, Papaver somniferum. The synthesis of morphine and its derivatives has attracted the attention of many generations of synthetic chemists due to their highly challenging molecular architecture and biological activities. Progresses toward the synthesis of the morphine alkaloids are reviewed in terms of chronological order.
2017, 37(7): 1653-1666
doi: 10.6023/cjoc201702017
Abstract:
Thiopeptide antibiotics, which are a growing class of sulfur-rich and highly modified polyazolyl peptide natural products, have been appreciated because of their complex structures, potent biological activities and unusual modes of action. Recently, a great deal of effort has been devoted to the development of various approaches for the efficient synthesis of thiopeptide antibiotics analogues. This review summarizes synthetic approaches towards thiopeptide antibiotics analogues via semisynthesis, combinatorial biosynthesis and precursor-directed mutasynthesis.
Thiopeptide antibiotics, which are a growing class of sulfur-rich and highly modified polyazolyl peptide natural products, have been appreciated because of their complex structures, potent biological activities and unusual modes of action. Recently, a great deal of effort has been devoted to the development of various approaches for the efficient synthesis of thiopeptide antibiotics analogues. This review summarizes synthetic approaches towards thiopeptide antibiotics analogues via semisynthesis, combinatorial biosynthesis and precursor-directed mutasynthesis.
2017, 37(7): 1667-1680
doi: 10.6023/cjoc201702009
Abstract:
Aryl/vinyl thioethers containing C(sp2)-S bonds are prevalent in biologically relevant molecules and compounds with other potential applications. Around the past decade, rapid progress has taken place in the research area of C(sp2)-S construction, and a large number of efficient new catalytic systems as well as structurally versatile substrates have been identified for such reactions, which significantly enriched the content of the synthetic methodologies on C(sp2)-S bond formation. This review introduces mainly the research advances on transition metal-free C(sp2)-S bond forming reaction by means of C(sp2)-H bond functionalization over the period of 2001~2016.
Aryl/vinyl thioethers containing C(sp2)-S bonds are prevalent in biologically relevant molecules and compounds with other potential applications. Around the past decade, rapid progress has taken place in the research area of C(sp2)-S construction, and a large number of efficient new catalytic systems as well as structurally versatile substrates have been identified for such reactions, which significantly enriched the content of the synthetic methodologies on C(sp2)-S bond formation. This review introduces mainly the research advances on transition metal-free C(sp2)-S bond forming reaction by means of C(sp2)-H bond functionalization over the period of 2001~2016.
2017, 37(7): 1681-1700
doi: 10.6023/cjoc201612062
Abstract:
The ocean is the most resource-rich area on earth. The living environment of marine life is complicated, so that they form a special structure of the active substances. Coupled with the progress of science and technology, people are increasingly concerned about how to find new active substances from marine life, which makes the marine bioactive peptide is widely concerned. Bioactive peptides have a variety of activities, the study shows that these substances have antioxidant, antihypertensive, anti-virus and anti-tumor activity. It has the advantages of low toxicity, high targeting specificity and strong biological activity. At present, some of bioactive peptides extracted from sea cucumbers, conus, ascidians, sponges, marine fungi, molluscs, or analogues derived from these compounds have entered the market or clinical stage. The current research status of marine bioactive peptides is reviewed including their source, synthetic method, chemical structure, activity, mechanism, clinical efficacy and safety. Research prospects in this field are discussed.
The ocean is the most resource-rich area on earth. The living environment of marine life is complicated, so that they form a special structure of the active substances. Coupled with the progress of science and technology, people are increasingly concerned about how to find new active substances from marine life, which makes the marine bioactive peptide is widely concerned. Bioactive peptides have a variety of activities, the study shows that these substances have antioxidant, antihypertensive, anti-virus and anti-tumor activity. It has the advantages of low toxicity, high targeting specificity and strong biological activity. At present, some of bioactive peptides extracted from sea cucumbers, conus, ascidians, sponges, marine fungi, molluscs, or analogues derived from these compounds have entered the market or clinical stage. The current research status of marine bioactive peptides is reviewed including their source, synthetic method, chemical structure, activity, mechanism, clinical efficacy and safety. Research prospects in this field are discussed.
2017, 37(7): 1701-1713
doi: 10.6023/cjoc201702011
Abstract:
Oridonin, an ent-kaurane diterpenoid, is found in the Chinese herb Rabdosia rubescens and some related species, and has various biological activities such as anti-tumor, anti-microbial, anti-inflammatory, and so on.This review provides an overview of the multifunctional effects of the structural modification of oridonin since 2000, suggesting that it may be effective choice for improving pharmacological activities.
Oridonin, an ent-kaurane diterpenoid, is found in the Chinese herb Rabdosia rubescens and some related species, and has various biological activities such as anti-tumor, anti-microbial, anti-inflammatory, and so on.This review provides an overview of the multifunctional effects of the structural modification of oridonin since 2000, suggesting that it may be effective choice for improving pharmacological activities.
2017, 37(7): 1714-1720
doi: 10.6023/cjoc201702037
Abstract:
An efficient CuCl/bpy-mediated atom transfer radical addition reaction of styrenes with CF3CHCl2 and CF3CCl3 is developed. Bpy which was added to enhance the reducibility of copper was crucial for activating one inert C-Cl bond of CF3CHCl2 and CF3CCl3 to form single radical adducts.
An efficient CuCl/bpy-mediated atom transfer radical addition reaction of styrenes with CF3CHCl2 and CF3CCl3 is developed. Bpy which was added to enhance the reducibility of copper was crucial for activating one inert C-Cl bond of CF3CHCl2 and CF3CCl3 to form single radical adducts.
2017, 37(7): 1721-1729
doi: 10.6023/cjoc201704006
Abstract:
Two kinds of novel pyrazole derivatives containing isatins, total of 12 target compounds, were prepared from 4-hydroxyacetophenone via addition, cyclization, substitution, hydrazinolysis and condensation, which were characterized by 1H NMR, 13C NMR and HRMS. The anti-neoplastic activity of target molecules was evaluated against human non-small cell lung cancer cell line A549 using cell counting Kit-8 (CCK-8) assay. The data showed that several compounds possessed potential anticancer effect. Among them, N'-(3-imino-6-chloroindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7e) and N'-(3-imino-6-bromoindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7f) exhibited IC50 values of 30.41 and 29.69 μmol/L, respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells, reduce the mitochondrial membrane potential, but have no effect on the cell cycle. Those data indicated that the anti-proliferative activity of molecule 7f was mediated by apoptosis-dependent mechanism involving the mitochondrial pathway in A549 cells.
Two kinds of novel pyrazole derivatives containing isatins, total of 12 target compounds, were prepared from 4-hydroxyacetophenone via addition, cyclization, substitution, hydrazinolysis and condensation, which were characterized by 1H NMR, 13C NMR and HRMS. The anti-neoplastic activity of target molecules was evaluated against human non-small cell lung cancer cell line A549 using cell counting Kit-8 (CCK-8) assay. The data showed that several compounds possessed potential anticancer effect. Among them, N'-(3-imino-6-chloroindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7e) and N'-(3-imino-6-bromoindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7f) exhibited IC50 values of 30.41 and 29.69 μmol/L, respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells, reduce the mitochondrial membrane potential, but have no effect on the cell cycle. Those data indicated that the anti-proliferative activity of molecule 7f was mediated by apoptosis-dependent mechanism involving the mitochondrial pathway in A549 cells.
2017, 37(7): 1730-1740
doi: 10.6023/cjoc201704005
Abstract:
A highly stereoselective[2, 3]-σ rearrangement of sulfur ylide derived from Cu(Ⅰ) carbene and allyl/propargyl sulfides (Doyle-Kirmse reaction) is reported. High stereocontrol is achieved by a dual asymmetric induction approach which involves a chiral auxiliary on diazo substrate, and steric bulky ligand of the Cu(Ⅰ) catalyst. From mechanistic study, we suggest the[2, 3]-σ rearrangement process occurs through free sulfur ylide intermediate. The reaction was further applied in kinetic resolution of allyl sulfide with a chiral center.
A highly stereoselective[2, 3]-σ rearrangement of sulfur ylide derived from Cu(Ⅰ) carbene and allyl/propargyl sulfides (Doyle-Kirmse reaction) is reported. High stereocontrol is achieved by a dual asymmetric induction approach which involves a chiral auxiliary on diazo substrate, and steric bulky ligand of the Cu(Ⅰ) catalyst. From mechanistic study, we suggest the[2, 3]-σ rearrangement process occurs through free sulfur ylide intermediate. The reaction was further applied in kinetic resolution of allyl sulfide with a chiral center.
2017, 37(7): 1748-1756
doi: 10.6023/cjoc201701038
Abstract:
Uric acid transporter 1 (URAT1) inhibitors bearing alkoxy group-substituted triazoles 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-methoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1a) and 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-ethoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1b) are structurally interesting lead compounds in drug design. The current synthetic approach to them suffers from quite low overall yields (3.3% and 3.0% for 1a and 1b, respectively). In order to explore the structure-activity relationship (SAR) of 1a and 1b, synthetic approach with higher overall yield is urgently needed. In the present study, two efficient synthetic approaches to 1a and 1b were developed (approaches A and B), with CuCl-catalyzed nucleophilic aromatic substitution (SNAr) reaction of bromotriazole with sodium alkoxides and SNAr reaction of methylsulfonyltriazole with sodium alkoxides as key steps, and the conditions for important steps were fully optimized. The two synthetic approaches are characterized by dramatically higher yields, and not only valuable to the further SAR exploration of 1a and 1b but also very helpful to the synthesis of heterocycles with alkoxyl groups.
Uric acid transporter 1 (URAT1) inhibitors bearing alkoxy group-substituted triazoles 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-methoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1a) and 3-(4-(4-cyclopropylnaphthalen-1-yl)-5-ethoxy-4H-1, 2, 4-triazol-3-yl)propanoic acid (1b) are structurally interesting lead compounds in drug design. The current synthetic approach to them suffers from quite low overall yields (3.3% and 3.0% for 1a and 1b, respectively). In order to explore the structure-activity relationship (SAR) of 1a and 1b, synthetic approach with higher overall yield is urgently needed. In the present study, two efficient synthetic approaches to 1a and 1b were developed (approaches A and B), with CuCl-catalyzed nucleophilic aromatic substitution (SNAr) reaction of bromotriazole with sodium alkoxides and SNAr reaction of methylsulfonyltriazole with sodium alkoxides as key steps, and the conditions for important steps were fully optimized. The two synthetic approaches are characterized by dramatically higher yields, and not only valuable to the further SAR exploration of 1a and 1b but also very helpful to the synthesis of heterocycles with alkoxyl groups.
2017, 37(7): 1757-1763
doi: 10.6023/cjoc201702012
Abstract:
1, 2, 3-Triazole aromatic oligomers are driven by intramolecular three-center C-H…O hydrogen bonding to form folded or helical secondary structures. This paper reports the assessment of their ability to form intermolecular C-H…Cl- in CDCl3 or C-H…N hydrogen bonding in CD2Cl2 by using 1H NMR. It is revealed that the two kinds of intramolecular six-membered C-H…O hydrogen bondings of the backbones are both weakened by Cl- through the formation of intermolecular C-H…Cl- hydrogen bonding. In the presence of excess of Cl-, the C-H…O hydrogen bonding on the N-1 side of the triazole units is, to a large extent, broken by intermolecular C-H…Cl- hydrogen bonding, which induces the backbones to form another kind of more extended crescent secondary structures. Under similar conditions, excess of Br- and I- can also form similar intermolecular hydrogen bonding. It is also found that the inside-located N-2 and N-3 atoms of the triazole units of a 8-mer oligomer can also form weak intermolecular C-H…N hydrogen bonding with C-H atoms of the alkynyl units of several tri-and bi-alkynes, which is enhanced by the folded conformation of the oligomer through forcing the N-2 and N-3 atoms to arrange into a ring.
1, 2, 3-Triazole aromatic oligomers are driven by intramolecular three-center C-H…O hydrogen bonding to form folded or helical secondary structures. This paper reports the assessment of their ability to form intermolecular C-H…Cl- in CDCl3 or C-H…N hydrogen bonding in CD2Cl2 by using 1H NMR. It is revealed that the two kinds of intramolecular six-membered C-H…O hydrogen bondings of the backbones are both weakened by Cl- through the formation of intermolecular C-H…Cl- hydrogen bonding. In the presence of excess of Cl-, the C-H…O hydrogen bonding on the N-1 side of the triazole units is, to a large extent, broken by intermolecular C-H…Cl- hydrogen bonding, which induces the backbones to form another kind of more extended crescent secondary structures. Under similar conditions, excess of Br- and I- can also form similar intermolecular hydrogen bonding. It is also found that the inside-located N-2 and N-3 atoms of the triazole units of a 8-mer oligomer can also form weak intermolecular C-H…N hydrogen bonding with C-H atoms of the alkynyl units of several tri-and bi-alkynes, which is enhanced by the folded conformation of the oligomer through forcing the N-2 and N-3 atoms to arrange into a ring.
2017, 37(7): 1764-1773
doi: 10.6023/cjoc201612042
Abstract:
A series of trifluoromethylated homoallylic N-acylhydrazines were obtained from one-pot reaction of aryl trifluoroketones, acylhydrazines and allyl bromide promoted by tin powder in the presence of boron trifluoride diethyl etherate (BF3·OEt2). The features of this process include good yields, wide substrate scope, mild conditions and easy operation. Trifluoromethylated homoallylic N-acylhydrazines are useful trifluoromethyl building blocks. They can be easily transformed into trifluoromethylated nitrogen-containing compounds.
A series of trifluoromethylated homoallylic N-acylhydrazines were obtained from one-pot reaction of aryl trifluoroketones, acylhydrazines and allyl bromide promoted by tin powder in the presence of boron trifluoride diethyl etherate (BF3·OEt2). The features of this process include good yields, wide substrate scope, mild conditions and easy operation. Trifluoromethylated homoallylic N-acylhydrazines are useful trifluoromethyl building blocks. They can be easily transformed into trifluoromethylated nitrogen-containing compounds.
2017, 37(7): 1774-1780
doi: 10.6023/cjoc201612030
Abstract:
In order to study the insecticidal activity of o-carboxamidobenzamide compounds, to investigate the structure-activity relationships of these compounds, 2-amino-3-hydroxypropionic acid and substituted 2-nitrobenzoic acid were used as starting materials to synthesize 29 diamides target compounds containing 2-substituted phenyloxazole groups, the yields were in the range of 30% and 50%. The insecticidal activities of these compounds were investigated. To some extend, the title compounds showed insecticidal activity against oriental armyworm (Mythimna separata Walker) in vitro. 2-(2-bromophenyl)-N-(4-chloro-2-(methoxy carbamoyl)-6-methyl phenyl) oxazole-4-carbox-amide (compound 11p) showed the highest insecticidal activity among these compounds. The structure-activity relationship of these compounds was summarized and the compounds with high activity were obtained.
In order to study the insecticidal activity of o-carboxamidobenzamide compounds, to investigate the structure-activity relationships of these compounds, 2-amino-3-hydroxypropionic acid and substituted 2-nitrobenzoic acid were used as starting materials to synthesize 29 diamides target compounds containing 2-substituted phenyloxazole groups, the yields were in the range of 30% and 50%. The insecticidal activities of these compounds were investigated. To some extend, the title compounds showed insecticidal activity against oriental armyworm (Mythimna separata Walker) in vitro. 2-(2-bromophenyl)-N-(4-chloro-2-(methoxy carbamoyl)-6-methyl phenyl) oxazole-4-carbox-amide (compound 11p) showed the highest insecticidal activity among these compounds. The structure-activity relationship of these compounds was summarized and the compounds with high activity were obtained.
2017, 37(7): 1781-1786
doi: 10.6023/cjoc201612045
Abstract:
The paper describes a convenient and facile methodology for the synthesis of 2, 5-diphenylthiophene derivatives. The environmentally friendly synthetic approach is supported by a one-pot tandem reaction process. All of the target products was confirmed by 1H NMR, 13C NMR and HRMS. On this basis, UV and fluorescence properties of the synthesized compounds were further explored. The experimental results showed that the UV maximum absorption wavelengths of the compounds are between 292 and 341 nm. The fluorescence spectra showed that these compounds have good fluorescence. The fluorescence emission wavelengths measured in methanol are between 386 and 454.5 nm, and the fluorescence emission wavelengths measured in dichloromethane are between 390 and 412 nm. The increase of conjugation system led to the red shift of fluorescence.
The paper describes a convenient and facile methodology for the synthesis of 2, 5-diphenylthiophene derivatives. The environmentally friendly synthetic approach is supported by a one-pot tandem reaction process. All of the target products was confirmed by 1H NMR, 13C NMR and HRMS. On this basis, UV and fluorescence properties of the synthesized compounds were further explored. The experimental results showed that the UV maximum absorption wavelengths of the compounds are between 292 and 341 nm. The fluorescence spectra showed that these compounds have good fluorescence. The fluorescence emission wavelengths measured in methanol are between 386 and 454.5 nm, and the fluorescence emission wavelengths measured in dichloromethane are between 390 and 412 nm. The increase of conjugation system led to the red shift of fluorescence.
2017, 37(7): 1787-1793
doi: 10.6023/cjoc201701037
Abstract:
Nine new heterozygous isatin-quinazoline compounds were synthesized from cheap and easily available ortho nitrobenzaldehyde as the starting material. The chemical structures of the synthesized compounds were characterized by NMR, IR and HRMS. The structure of (E)-3-(((E)-(5-(4-((3-ethynylphenyl)amino)quinazolin-6-yl)furan-2-yl)methylene)hydrazono)-indolin-2-one (4a) was further determined by crystallization and X-ray diffraction, and the data revealed that its cis-trans isomerism was (E, E). The antitumor activity of these new compounds was evaluated in vitro by methyl thiazolyl tetrazolium (MTT) assay in human colorectal carcinoma cells SW480, human non-small cell lung cancer cells A549 and NCI- H1975, and human epidermoid squamous carcinoma cells A431. The preliminary data demonstrated that most of the synthetic compounds had moderate to potent inhibitory activity against these four tumor cell lines. In particular, compound 4a had highly potent inhibitory activity on proliferation of four cell lines, and the activity was more potent than positive lapatinib.
Nine new heterozygous isatin-quinazoline compounds were synthesized from cheap and easily available ortho nitrobenzaldehyde as the starting material. The chemical structures of the synthesized compounds were characterized by NMR, IR and HRMS. The structure of (E)-3-(((E)-(5-(4-((3-ethynylphenyl)amino)quinazolin-6-yl)furan-2-yl)methylene)hydrazono)-indolin-2-one (4a) was further determined by crystallization and X-ray diffraction, and the data revealed that its cis-trans isomerism was (E, E). The antitumor activity of these new compounds was evaluated in vitro by methyl thiazolyl tetrazolium (MTT) assay in human colorectal carcinoma cells SW480, human non-small cell lung cancer cells A549 and NCI- H1975, and human epidermoid squamous carcinoma cells A431. The preliminary data demonstrated that most of the synthetic compounds had moderate to potent inhibitory activity against these four tumor cell lines. In particular, compound 4a had highly potent inhibitory activity on proliferation of four cell lines, and the activity was more potent than positive lapatinib.
2017, 37(7): 1800-1807
doi: 10.6023/cjoc201701045
Abstract:
A novel method based on reaction of β-ketothioamides (KTAs) with malononitrile to construct thiazolylidenes has been developed under metal-free conditions. This method used cheap tetrabutylammonium iodide (TBAI) as catalyst and t-butylhydroperoxide (TBHP) as oxidant in the presence of Et3N at room temperature for 1 h to synthesize a series of 4-aminothiazolylidene derivatives in good yields. This reaction has some advantages such as simple operation, mild reaction conditions, short reaction time, environmentally benign and simple work-up.
A novel method based on reaction of β-ketothioamides (KTAs) with malononitrile to construct thiazolylidenes has been developed under metal-free conditions. This method used cheap tetrabutylammonium iodide (TBAI) as catalyst and t-butylhydroperoxide (TBHP) as oxidant in the presence of Et3N at room temperature for 1 h to synthesize a series of 4-aminothiazolylidene derivatives in good yields. This reaction has some advantages such as simple operation, mild reaction conditions, short reaction time, environmentally benign and simple work-up.
2017, 37(7): 1808-1813
doi: 10.6023/cjoc201612008
Abstract:
A series of difurylarylmethanes were prepared in high yields by condensation of 2-methylfuran with aromatic aldehydes in the presence of bromodimethylsufonium bromide (BMDS) at room temperature under solvent-free conditions. All products were characterized by 1H NMR and 13C NMR spectra.
A series of difurylarylmethanes were prepared in high yields by condensation of 2-methylfuran with aromatic aldehydes in the presence of bromodimethylsufonium bromide (BMDS) at room temperature under solvent-free conditions. All products were characterized by 1H NMR and 13C NMR spectra.
2017, 37(7): 1814-1823
doi: 10.6023/cjoc201610045
Abstract:
Pyropheophorbide-a (b) methyl esters were used as starting materials to form different chlorophyll degradation products by the modification of the exocyclic ring and the metallization of the chromophore. The new functional groups were introduced at 20-position via the Vilsmeier acylation and the Blanc hydroxymethylation. The active structures of chlorin peripheries were oxidized using osmium tetroxide, thaillum nitrate and air as oxidizing agent to introduce the formyl group and the formylmethyl group at 3-, 7-or 12-postion and on the exocyclic ring, respectively. A series of unreported chlorin aldehydes related to chlorophyll were synthesized and their chemical structures were characterized by elemental analysis, UV, IR and 1H NMR spectra. The reaction mechanisms on the hydroformylation for the chlorophyllous chlorins were discussed and the interactions of new compounds with bovine serum albumins were researched.
Pyropheophorbide-a (b) methyl esters were used as starting materials to form different chlorophyll degradation products by the modification of the exocyclic ring and the metallization of the chromophore. The new functional groups were introduced at 20-position via the Vilsmeier acylation and the Blanc hydroxymethylation. The active structures of chlorin peripheries were oxidized using osmium tetroxide, thaillum nitrate and air as oxidizing agent to introduce the formyl group and the formylmethyl group at 3-, 7-or 12-postion and on the exocyclic ring, respectively. A series of unreported chlorin aldehydes related to chlorophyll were synthesized and their chemical structures were characterized by elemental analysis, UV, IR and 1H NMR spectra. The reaction mechanisms on the hydroformylation for the chlorophyllous chlorins were discussed and the interactions of new compounds with bovine serum albumins were researched.
2017, 37(7): 1824-1829
doi: 10.6023/cjoc201612032
Abstract:
The furoquinoline unit is present in many natural products. Here, an approach is presented for the preparing of furo[2, 3-b]quinolines from readily available multi-substituted furans in the presence of Brønsted acid via an intramolecular cyclization under the heating conditions. Simple operation, good compatibility, high regioselectivity and morderate yields are the advantages of the method.
The furoquinoline unit is present in many natural products. Here, an approach is presented for the preparing of furo[2, 3-b]quinolines from readily available multi-substituted furans in the presence of Brønsted acid via an intramolecular cyclization under the heating conditions. Simple operation, good compatibility, high regioselectivity and morderate yields are the advantages of the method.
2017, 37(7): 1741-1747
doi: 10.6023/cjoc201701005
Abstract:
In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by 1H NMR, 13C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a~5h exhibited potent cytotoxic activities with IC50 values lower than 10 μmol·L-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC50 values of 0.8 μmol·L-1 and 0.6 μmol·L-1, respectively.
In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by 1H NMR, 13C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a~5h exhibited potent cytotoxic activities with IC50 values lower than 10 μmol·L-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC50 values of 0.8 μmol·L-1 and 0.6 μmol·L-1, respectively.
2017, 37(7): 1794-1799
doi: 10.6023/cjoc201701039
Abstract:
Two novel N-heterocyclic carbene-palladium(Ⅱ) complexes were conveniently synthesized through one-pot reactions of imidazolium salts, palladium chloride and acridine. The new complexes have been fully characterized by 1H NMR, 13C NMR, elemental analysis, and X-ray single-crystal diffraction. Moreover, the obtained palladium(Ⅱ) complexes were the effective catalyst precursors for the Suzuki-Miyaura coupling of aryl as well as benzyl chlorides with arylboronic acids. Under the optimal conditions, all reactions proceeded successfully to give the desired products in good to almost quantitative yields.
Two novel N-heterocyclic carbene-palladium(Ⅱ) complexes were conveniently synthesized through one-pot reactions of imidazolium salts, palladium chloride and acridine. The new complexes have been fully characterized by 1H NMR, 13C NMR, elemental analysis, and X-ray single-crystal diffraction. Moreover, the obtained palladium(Ⅱ) complexes were the effective catalyst precursors for the Suzuki-Miyaura coupling of aryl as well as benzyl chlorides with arylboronic acids. Under the optimal conditions, all reactions proceeded successfully to give the desired products in good to almost quantitative yields.
2017, 37(7): 1830-1834
doi: 10.6023/cjoc201703042
Abstract:
Methyl group is the smallest carbon substituent that plays important roles in many compounds. Conversion of a carboxylic acid into a ketone is a fundamental transformation in organic chemistry. This functional group change is usually performed indirectly by activating the carboxylic acid into an acyl chloride or into a Weinreb amide, and then by nucleophilic attack with an organometallic reagent. However, direct conversion of a carboxylic acid into a ketone can be achieved in one-step reaction using at least 2 equiv. of an organolithium reagent at low temperature and producing much tertiary alcohol. Herein, methylation of alkyl acid under Ni-catalyzed reductive coupling conditions using methyl p-methyl tosylate as the methylation reagent was reported to yield methylated ketones. Moderate yields as well as good functional group tolerance were observed under the present mild and easy-to-operate reaction conditions.
Methyl group is the smallest carbon substituent that plays important roles in many compounds. Conversion of a carboxylic acid into a ketone is a fundamental transformation in organic chemistry. This functional group change is usually performed indirectly by activating the carboxylic acid into an acyl chloride or into a Weinreb amide, and then by nucleophilic attack with an organometallic reagent. However, direct conversion of a carboxylic acid into a ketone can be achieved in one-step reaction using at least 2 equiv. of an organolithium reagent at low temperature and producing much tertiary alcohol. Herein, methylation of alkyl acid under Ni-catalyzed reductive coupling conditions using methyl p-methyl tosylate as the methylation reagent was reported to yield methylated ketones. Moderate yields as well as good functional group tolerance were observed under the present mild and easy-to-operate reaction conditions.
2017, 37(7): 1835-1838
doi: 10.6023/cjoc201612055
Abstract:
A novel, efficient and straightforward method to synthesize 1, 4-dihydropyridine compounds with excellent yields is reported through Hantzsch reaction of aldehydes, ammonium acetate and ethyl acetoacetate or methyl acetoacetate using humic acid as the catalyst. This method has high yield and less pollution. The catalyst is easy to recycle and environment friendly.
A novel, efficient and straightforward method to synthesize 1, 4-dihydropyridine compounds with excellent yields is reported through Hantzsch reaction of aldehydes, ammonium acetate and ethyl acetoacetate or methyl acetoacetate using humic acid as the catalyst. This method has high yield and less pollution. The catalyst is easy to recycle and environment friendly.
2017, 37(7): 1839-1843
doi: 10.6023/cjoc201702021
Abstract:
A new C18 diterpenoid alkaloid, leucostonine (1), was isolated from the whole plant of Aconitum leucostomum Vorosch., together with twelve known diterpenoid alkaloids. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, 1D NMR and 2D NMR spectra. 12 compounds were tested for their antifeedant activity against larvae of Spodoptera exigua Hiibner. Anthranoyllycoctonine and avadharidine showed considerable potent antifeedant activity (EC50 < 1 mg/cm2), followed by N-acetylsepaconitine, finaconitine and N-deacetylappaconitine (EC50 < 2 mg/cm2).
A new C18 diterpenoid alkaloid, leucostonine (1), was isolated from the whole plant of Aconitum leucostomum Vorosch., together with twelve known diterpenoid alkaloids. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, 1D NMR and 2D NMR spectra. 12 compounds were tested for their antifeedant activity against larvae of Spodoptera exigua Hiibner. Anthranoyllycoctonine and avadharidine showed considerable potent antifeedant activity (EC50 < 1 mg/cm2), followed by N-acetylsepaconitine, finaconitine and N-deacetylappaconitine (EC50 < 2 mg/cm2).
2017, 37(7): 1844-1849
doi: 10.6023/cjoc201702006
Abstract:
In order to find new pesticide with potent bioactivities, a series of novel pyrazole amides carrying 1, 3, 4-oxadiazole moiety were prepared according to the structure of tebufenpyrad. The structures of the title compounds were characterized by 1H NMR, 13C NMR and elemental analysis. Preliminary bioassay data showed that some target compounds displayed good insecticidal activities. At the concentration of 500 μg/mL, five compounds had insecticidal activity against Oriental armyworm with 80%~100%, and four compounds displayed comparable insecticidal activity against Oriental armyworm to that of the control tolfenpyrad. In addition, 1-methyl-3-ethyl-4-chloro-N-{[5-(4-methylphenyl)-1, 3, 4-oxadiazol-2-yl)methyl]-1H-pyrazole-5-carboxamide (9g) exhibited 100% insecticidal activity against Aphis medicaginis at 500 μg/mL.
In order to find new pesticide with potent bioactivities, a series of novel pyrazole amides carrying 1, 3, 4-oxadiazole moiety were prepared according to the structure of tebufenpyrad. The structures of the title compounds were characterized by 1H NMR, 13C NMR and elemental analysis. Preliminary bioassay data showed that some target compounds displayed good insecticidal activities. At the concentration of 500 μg/mL, five compounds had insecticidal activity against Oriental armyworm with 80%~100%, and four compounds displayed comparable insecticidal activity against Oriental armyworm to that of the control tolfenpyrad. In addition, 1-methyl-3-ethyl-4-chloro-N-{[5-(4-methylphenyl)-1, 3, 4-oxadiazol-2-yl)methyl]-1H-pyrazole-5-carboxamide (9g) exhibited 100% insecticidal activity against Aphis medicaginis at 500 μg/mL.
2017, 37(7): 1850-1854
doi: 10.6023/cjoc201612057
Abstract:
A novel approach for the synthesis of tetra-substituted naphthalenes is demonstrated through the ligand-free coupling of a wide range of alkynes with Grignard reagents catalyzed by NiCl2, avoiding the use of special ligands and expensive catalysts used in previous methods. Other outstanding features include mild reaction conditions, good yields and wide functional group tolerance. The protocol provides an efficient method for the synthesis of highly substituted naphthalenes.
A novel approach for the synthesis of tetra-substituted naphthalenes is demonstrated through the ligand-free coupling of a wide range of alkynes with Grignard reagents catalyzed by NiCl2, avoiding the use of special ligands and expensive catalysts used in previous methods. Other outstanding features include mild reaction conditions, good yields and wide functional group tolerance. The protocol provides an efficient method for the synthesis of highly substituted naphthalenes.
2017, 37(7): 1855-1859
doi: 10.6023/cjoc201701013
Abstract:
In this paper, the homogeneous catalytic system of CuSO4·5H2O/NaAsc was used to realize the Sonogashira reaction of aryl iodides and terminal alkynes. This catalytic system replaces the general catalytic system of Pd/Cu-bound phosphorus ligand, which has the advantages of cheap catalyst, simple post-treatment, reaction under homogeneous conditions, and meets the requirements of green chemistry.
In this paper, the homogeneous catalytic system of CuSO4·5H2O/NaAsc was used to realize the Sonogashira reaction of aryl iodides and terminal alkynes. This catalytic system replaces the general catalytic system of Pd/Cu-bound phosphorus ligand, which has the advantages of cheap catalyst, simple post-treatment, reaction under homogeneous conditions, and meets the requirements of green chemistry.
2017, 37(7): 1860-1863
doi: 10.6023/cjoc201701002
Abstract:
One new, dabeshanensin L (1), and nine known diterpenoids with diverse structures were isolated from the 90% MeOH extract of the needles (30 g dried mass-limited samples) of Pinus dabeshanensis, an endangered conifer listed in the China Plant Red Data Book (CPRDB). The new structure was established by detailed analysis of its spectroscopic data (IR, 1D/2D NMR, HRMS). Among the isolates, isopimara-7-en-18-oic acid (4), trans-abienol (6), and lambertianic acid (8) showed significant inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B) enzyme, a key target for the treatment of type-Ⅱ diabetes and obesity, with IC50 values ranging from 14.6 to 37.7 μmol/L.
One new, dabeshanensin L (1), and nine known diterpenoids with diverse structures were isolated from the 90% MeOH extract of the needles (30 g dried mass-limited samples) of Pinus dabeshanensis, an endangered conifer listed in the China Plant Red Data Book (CPRDB). The new structure was established by detailed analysis of its spectroscopic data (IR, 1D/2D NMR, HRMS). Among the isolates, isopimara-7-en-18-oic acid (4), trans-abienol (6), and lambertianic acid (8) showed significant inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B) enzyme, a key target for the treatment of type-Ⅱ diabetes and obesity, with IC50 values ranging from 14.6 to 37.7 μmol/L.
2017, 37(7): 1864-1869
doi: 10.6023/cjoc201701012
Abstract:
A metal-free method (KOH/DMSO) for the synthesis of o-halodiarylamines from o-halophenols and 2-bromo-N-arylpropanamide via Smiles rearrangement reaction as a key step has been developed in this paper. This method has advantages of simple and efficient operation, easy available starting materials and transition-metal-free conditions. It exhibits the certain application value. Using this method, a series of o-halodiarylamines have been synthesized in 23%~81% yields.
A metal-free method (KOH/DMSO) for the synthesis of o-halodiarylamines from o-halophenols and 2-bromo-N-arylpropanamide via Smiles rearrangement reaction as a key step has been developed in this paper. This method has advantages of simple and efficient operation, easy available starting materials and transition-metal-free conditions. It exhibits the certain application value. Using this method, a series of o-halodiarylamines have been synthesized in 23%~81% yields.
2017, 37(7): 1870-1876
doi: 10.6023/cjoc201612043
Abstract:
How to promote polyhedral oligomeric silsesquioxanes (POSS) compatibility with polymers is always the key point of the research on POSS. Introduction of nitro groups into the POSS by nitration is an important method for improving the compatibility between POSS and other polymers. GPC, TGA, 1H NMR, FTIR and element analysis were used to characterize the structures of the products nitrated from cyclic ladder polyphenylsilsesquioxane (CL-PPSQ) by several kinds of nitration agents, including fuming nitric acid, HNO3-H2SO4, KNO3-H2SO4 and HNO3-(CH3CO)2O. The results showed that NO2-CL-PPSQ was prepared using 75% HNO3-(CH3CO)2O through a moderate nitration process, meanwhile the cyclic structure of PPSQ was remained, and NO2-CL-PPSQ of one nitryl group on every phenyl could be prepared. At the same time, the nitration mechanisms using different nitration reagents were analyzed. NO2+, which broke the chemical structure of CL-PPSQ, could be found in the fuming nitric acid and H2SO4-HNO3 (KNO3) systems. With regard to the HNO3-(CH3CO)2O system, the main activator was CH3COONO2 which had appropriate nitration ability. In brief, cyclic ladder polynitrophenylsilsesquioxanes have good solubility in organic solvent, good dispersion in the resin matrix and nitro groups with reaction activity at the same time. The successful synthesis of this polymer provides a precursor for subsequent amination, alkynyl, azide reaction.
How to promote polyhedral oligomeric silsesquioxanes (POSS) compatibility with polymers is always the key point of the research on POSS. Introduction of nitro groups into the POSS by nitration is an important method for improving the compatibility between POSS and other polymers. GPC, TGA, 1H NMR, FTIR and element analysis were used to characterize the structures of the products nitrated from cyclic ladder polyphenylsilsesquioxane (CL-PPSQ) by several kinds of nitration agents, including fuming nitric acid, HNO3-H2SO4, KNO3-H2SO4 and HNO3-(CH3CO)2O. The results showed that NO2-CL-PPSQ was prepared using 75% HNO3-(CH3CO)2O through a moderate nitration process, meanwhile the cyclic structure of PPSQ was remained, and NO2-CL-PPSQ of one nitryl group on every phenyl could be prepared. At the same time, the nitration mechanisms using different nitration reagents were analyzed. NO2+, which broke the chemical structure of CL-PPSQ, could be found in the fuming nitric acid and H2SO4-HNO3 (KNO3) systems. With regard to the HNO3-(CH3CO)2O system, the main activator was CH3COONO2 which had appropriate nitration ability. In brief, cyclic ladder polynitrophenylsilsesquioxanes have good solubility in organic solvent, good dispersion in the resin matrix and nitro groups with reaction activity at the same time. The successful synthesis of this polymer provides a precursor for subsequent amination, alkynyl, azide reaction.
2017, 37(7): 1877-1882
doi: 10.6023/cjoc201612048
Abstract:
In an attempt to discover novel fuse heterocyclic compound with high herbicidal activity, sixteen newly 2-alkythio-thieno[2, 3-d]pyrimidin-4(3H)-ones have been designed and synthesized by the reaction of 3-propyl-6-ethylthieno[2, 3-d]pyrimidine-2-thione with halo-hydrocarbon. Their structures were clearly verified by 1H NMR, IR, LC-MS and elemental analysis. Preliminary bioassay results indicate that some target compounds have excellent inhibitory activities on barnyard grass and rape. 2-Cyclopentylthio-3-n-propyl-6-ethylthieno[2, 3-d]pyrimidin-4(3H)-one (4e) and 2-n-hexdecylthio-3-n-propyl-6-ethylthieno[2, 3-d]pyrimidin-4(3H)-one (4o) show 100% inhibition rate to barnyard grass at the concentration of 100 mg/L.
In an attempt to discover novel fuse heterocyclic compound with high herbicidal activity, sixteen newly 2-alkythio-thieno[2, 3-d]pyrimidin-4(3H)-ones have been designed and synthesized by the reaction of 3-propyl-6-ethylthieno[2, 3-d]pyrimidine-2-thione with halo-hydrocarbon. Their structures were clearly verified by 1H NMR, IR, LC-MS and elemental analysis. Preliminary bioassay results indicate that some target compounds have excellent inhibitory activities on barnyard grass and rape. 2-Cyclopentylthio-3-n-propyl-6-ethylthieno[2, 3-d]pyrimidin-4(3H)-one (4e) and 2-n-hexdecylthio-3-n-propyl-6-ethylthieno[2, 3-d]pyrimidin-4(3H)-one (4o) show 100% inhibition rate to barnyard grass at the concentration of 100 mg/L.
