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2017 Volume 37 Issue 2
2017, 37(2): 251-266
doi: 10.6023/cjoc201609022
Abstract:
Visible-light-promoted oxygenation reactions using dioxygen as a terminal oxidant have the advantage of mild reaction conditions and environmental-friendly. Visible-light-promoted aerobic oxygenation reactions of alkanes, alkenes, alkynes, alcohols, aldehydes and other hetero-atom containing functional groups are reviewed.
Visible-light-promoted oxygenation reactions using dioxygen as a terminal oxidant have the advantage of mild reaction conditions and environmental-friendly. Visible-light-promoted aerobic oxygenation reactions of alkanes, alkenes, alkynes, alcohols, aldehydes and other hetero-atom containing functional groups are reviewed.
2017, 37(2): 267-283
doi: 10.6023/cjoc201608014
Abstract:
The formation of amide bond is one of the most key reactions in organic chemistry. How to generate amide bond economically is often overlooked as a contemporary challenge as a result of the widespread occurrence of amide polymers, natural products marketed drugs as well as synthetic intermediates. There are inherent drawbacks in the methods. Concerns about their waste and expense are becoming sharper. Thus, Novel chemical protocols to amide formation are being raised. Among a large amount of ways of preparing a amide bond, there has been a growing attention in the use of catalyzed methods for preparing such important functional group. In this review, the catalyst for the formation of an amide bond has become the highlight of some the latest literature in key areas. Alcohols, aldehydes, ketones, unsaturated hydrocarbons, etc., react with organic amines or inorganic amines under a variety of conditions to give the corresponding amide. The review of a new generation of amide-forming reactions may be beneficial to solving these problems.
The formation of amide bond is one of the most key reactions in organic chemistry. How to generate amide bond economically is often overlooked as a contemporary challenge as a result of the widespread occurrence of amide polymers, natural products marketed drugs as well as synthetic intermediates. There are inherent drawbacks in the methods. Concerns about their waste and expense are becoming sharper. Thus, Novel chemical protocols to amide formation are being raised. Among a large amount of ways of preparing a amide bond, there has been a growing attention in the use of catalyzed methods for preparing such important functional group. In this review, the catalyst for the formation of an amide bond has become the highlight of some the latest literature in key areas. Alcohols, aldehydes, ketones, unsaturated hydrocarbons, etc., react with organic amines or inorganic amines under a variety of conditions to give the corresponding amide. The review of a new generation of amide-forming reactions may be beneficial to solving these problems.
2017, 37(2): 284-300
doi: 10.6023/cjoc201607035
Abstract:
The addition of carbon-hetero bonds to alkynes has become an important apporach for the functionalization of carbon-carbon triple bonds. It can construct two bonds, namely one carbon-carbon bond and one carbon-hetero bond, in a single one step. These addition reactions feature high efficiency and high atom-economy. In recent years, metal-catalyzed (Al, Fe, Ni, Cu, Ga, Ru, Rh, Pd, Hf, Ir, Pt, Au, Bi, etc.) addition of many various kinds of carbon-hetero bonds to alkynes has achieved lots of important developments. According to the types of carbon-hetero bonds, the addition of 8 different kinds of carbon-hetero bonds [C-H, C-B, C-N, C-O, C-Si, C-S, C-X (X=Cl, Br, I), C-Se] to alkynes is reviewed in this paper, and the reaction conditions, reaction selectivities (regioselectivities and stereoselectivities) and reaction mechanisms are also discussed and summarized.
The addition of carbon-hetero bonds to alkynes has become an important apporach for the functionalization of carbon-carbon triple bonds. It can construct two bonds, namely one carbon-carbon bond and one carbon-hetero bond, in a single one step. These addition reactions feature high efficiency and high atom-economy. In recent years, metal-catalyzed (Al, Fe, Ni, Cu, Ga, Ru, Rh, Pd, Hf, Ir, Pt, Au, Bi, etc.) addition of many various kinds of carbon-hetero bonds to alkynes has achieved lots of important developments. According to the types of carbon-hetero bonds, the addition of 8 different kinds of carbon-hetero bonds [C-H, C-B, C-N, C-O, C-Si, C-S, C-X (X=Cl, Br, I), C-Se] to alkynes is reviewed in this paper, and the reaction conditions, reaction selectivities (regioselectivities and stereoselectivities) and reaction mechanisms are also discussed and summarized.
2017, 37(2): 301-313
doi: 10.6023/cjoc201607046
Abstract:
Frustrated Lewis pairs (FLPs) catalyzed hydrogenation reaction is one of the hotspots in the current hydrogenation field. This kind of reaction has the advantages of environment friendly, no metal residue, etc., and has a potential prospect for industrial application. According to the category of the substrate, a brief review of the recent progress in the field of the FLPs-catalyzed hydrogenation as well as the asymmetric hydrogenation is depicted.
Frustrated Lewis pairs (FLPs) catalyzed hydrogenation reaction is one of the hotspots in the current hydrogenation field. This kind of reaction has the advantages of environment friendly, no metal residue, etc., and has a potential prospect for industrial application. According to the category of the substrate, a brief review of the recent progress in the field of the FLPs-catalyzed hydrogenation as well as the asymmetric hydrogenation is depicted.
2017, 37(2): 314-334
doi: 10.6023/cjoc201608009
Abstract:
Transition-metal-catalyzed coupling reactions play an important role in construct C-C bond. As one of the most abundant metal in the earth's crust, along with its inexpensive price, relatively low toxicity and multiple redox states, Fe is an ideal catalyst for coupling reactions. Recently, green, highly effective and selective reactions have attracted much attention, which accelerated the research of iron catalyzed coupling. Particularly, many new catalyst systems and various reaction types such as iron catalyzed oxidative coupling, reductive coupling and C-H direct functionalization were explored during the past decade. The present review surveys the recent progress in Fe catalyzed C-C coupling concerning their reaction types, including mechanism and application. Furthermore, the prospects of this reaction are also discussed.
Transition-metal-catalyzed coupling reactions play an important role in construct C-C bond. As one of the most abundant metal in the earth's crust, along with its inexpensive price, relatively low toxicity and multiple redox states, Fe is an ideal catalyst for coupling reactions. Recently, green, highly effective and selective reactions have attracted much attention, which accelerated the research of iron catalyzed coupling. Particularly, many new catalyst systems and various reaction types such as iron catalyzed oxidative coupling, reductive coupling and C-H direct functionalization were explored during the past decade. The present review surveys the recent progress in Fe catalyzed C-C coupling concerning their reaction types, including mechanism and application. Furthermore, the prospects of this reaction are also discussed.
2017, 37(2): 335-348
doi: 10.6023/cjoc201608030
Abstract:
Organophosphorus compounds which contain P-C bonds have been widely used in photoelectric materials, retardant materials and medicinal chemistry. It is an important method for the synthesis of functional organophosphorus compounds from P (O)-H reagents using transition metal-catalyzed cross coupling reaction to form P-C bond. The recent development in this area is summarized on the basis of different types of carbon atom.
Organophosphorus compounds which contain P-C bonds have been widely used in photoelectric materials, retardant materials and medicinal chemistry. It is an important method for the synthesis of functional organophosphorus compounds from P (O)-H reagents using transition metal-catalyzed cross coupling reaction to form P-C bond. The recent development in this area is summarized on the basis of different types of carbon atom.
2017, 37(2): 349-355
doi: 10.6023/cjoc201607043
Abstract:
Acetone is the simplest ketone, which has the typical reaction of ketones. In this paper, the recent development centering the coupling reactions of acetone including the formation of carbon-carbon, carbon-heteroatom bonds and the discussion of reaction mechanism, is reviewed.
Acetone is the simplest ketone, which has the typical reaction of ketones. In this paper, the recent development centering the coupling reactions of acetone including the formation of carbon-carbon, carbon-heteroatom bonds and the discussion of reaction mechanism, is reviewed.
2017, 37(2): 356-374
doi: 10.6023/cjoc201607004
Abstract:
Lysosomes are vital in many physiological processes such as metabolism, membrane repair, cell apoptosis, etc. To have lysosomes visualized and reactive small molecules (RSMs) detected are of great significance on the understanding of some intracellular dynamic procedures as well as the therapy of related deseases. In the past few years, many lysosome-targeting RSMs-sensing fluorescent probes are reported, including protons, reduction species, oxidation species, metal cations, anions, enzymes and some physical properties such as pH, viscosity and temperature. The mechanism of targeting lysosomes can be classified into three types: (1) based on the acidic physiological environments in lysosomes, (2) based on the pathway of substance metabolism, especially the endocytosis of materials, and (3) based on the specific membrane proteins and hydrolases in lysosomes. The recently reported lysosomal fluorescent probes were assorted, summarized and reviewed in this work. The bright prospects of these probes in the application of preliminary diagnosis and therapy of some diseases were also discussed.
Lysosomes are vital in many physiological processes such as metabolism, membrane repair, cell apoptosis, etc. To have lysosomes visualized and reactive small molecules (RSMs) detected are of great significance on the understanding of some intracellular dynamic procedures as well as the therapy of related deseases. In the past few years, many lysosome-targeting RSMs-sensing fluorescent probes are reported, including protons, reduction species, oxidation species, metal cations, anions, enzymes and some physical properties such as pH, viscosity and temperature. The mechanism of targeting lysosomes can be classified into three types: (1) based on the acidic physiological environments in lysosomes, (2) based on the pathway of substance metabolism, especially the endocytosis of materials, and (3) based on the specific membrane proteins and hydrolases in lysosomes. The recently reported lysosomal fluorescent probes were assorted, summarized and reviewed in this work. The bright prospects of these probes in the application of preliminary diagnosis and therapy of some diseases were also discussed.
2017, 37(2): 375-384
doi: 10.6023/cjoc201608010
Abstract:
Epilactose (4-O-β-D-galactopyranosyl-D-mannose) is a reducing disaccharide with satisfactory prebiotic properties. A superior synthetic methods were confirmed by screening different coupled donors and acceptors which were synthesized from D-mannose and D-galactose, respectively. This route gets 50% overall yields and all the intermediates are easily to be purified, making the route suitable for large scale preparation of the target compound. All the compounds were characterized by NMR and HRMS spectra.
Epilactose (4-O-β-D-galactopyranosyl-D-mannose) is a reducing disaccharide with satisfactory prebiotic properties. A superior synthetic methods were confirmed by screening different coupled donors and acceptors which were synthesized from D-mannose and D-galactose, respectively. This route gets 50% overall yields and all the intermediates are easily to be purified, making the route suitable for large scale preparation of the target compound. All the compounds were characterized by NMR and HRMS spectra.
2017, 37(2): 385-393
doi: 10.6023/cjoc201608031
Abstract:
A series of quinazolin-4(3H)-one derivatives 4 and 5 possessing amino alkyl side chain were synthesized by the condensation reaction of 2-aminobenzamide with substituted benzaldehyde, followed by SN2 substitution reaction with haloalkane. The effects of the substituent at C-2 phenyl on the N-/O-alkylated reaction of quinazolin-4(3H)-one were explored. Some compounds were also evaluated for their anti proliferation activities and antimicrobial activities. The results showed that when the substituent was at orth O-position on C-2 phenyl, N-alkylation was the main reaction, while at meta-or para-positions, O-alkylation was predominant, which suggested that the steric factor played a key role on this ambident nuclophilic substitution. 4-(2-((2-(3-(Benzyloxy) phenyl) quinazolin-4-yl) oxy) ethyl) morpholine (4h) showed relatively good anti-proliferative activity against A549 tumor cells with the IC50 value of 13.20 μmol/L. 2-(2-Chlorophenyl)-3-(2-(piperidin-1-yl) ethyl) quinazolin-4(3H)-one (5aa) and 2-(3-(benzyloxy) phenyl)-4-(2-(pyrrolidin-1-yl) ethoxy) quinazoline (4hb) exhibited significant anti Esche-richia coli or Shigella castellani activities, and the inhibition rates were near 100% at the concentration of 50 μg/mL. The inhi-bition rate of compound 5aa against Alternaria alternate was 100%.
A series of quinazolin-4(3H)-one derivatives 4 and 5 possessing amino alkyl side chain were synthesized by the condensation reaction of 2-aminobenzamide with substituted benzaldehyde, followed by SN2 substitution reaction with haloalkane. The effects of the substituent at C-2 phenyl on the N-/O-alkylated reaction of quinazolin-4(3H)-one were explored. Some compounds were also evaluated for their anti proliferation activities and antimicrobial activities. The results showed that when the substituent was at orth O-position on C-2 phenyl, N-alkylation was the main reaction, while at meta-or para-positions, O-alkylation was predominant, which suggested that the steric factor played a key role on this ambident nuclophilic substitution. 4-(2-((2-(3-(Benzyloxy) phenyl) quinazolin-4-yl) oxy) ethyl) morpholine (4h) showed relatively good anti-proliferative activity against A549 tumor cells with the IC50 value of 13.20 μmol/L. 2-(2-Chlorophenyl)-3-(2-(piperidin-1-yl) ethyl) quinazolin-4(3H)-one (5aa) and 2-(3-(benzyloxy) phenyl)-4-(2-(pyrrolidin-1-yl) ethoxy) quinazoline (4hb) exhibited significant anti Esche-richia coli or Shigella castellani activities, and the inhibition rates were near 100% at the concentration of 50 μg/mL. The inhi-bition rate of compound 5aa against Alternaria alternate was 100%.
2017, 37(2): 394-402
doi: 10.6023/cjoc201606040
Abstract:
Four asymmetric hydrogen-bond acceptors of 1, 4-bis[2-(4-pyridyl) ethenyl]benzene derivatives with higher yields were synthesized through the classical Witting-Horner and Sonogashira cross-coupling reactions, and their structures and spectral properties were investigated. The series of compounds all have been characterized by NMR, MS and element analysis. Crystal structures indicated that the conformation of hydrogen-bond self-assemble may be change due to the hindrance effect from the arylacetyl group in o-position of benzene. UV-Vis spectra combined with time-dependent density functional theory (TDDFT) calculation results showed that target compounds all display a strong π→π* and ICT transition absorptions. Fluorescence spectrum indicated that gradual increasing of conjugate systems make their emission peak tend to a red shift, which is conducive to π-π accumulation. Above results will provide certain synthetic basis and theoretical foundation for subsequent studies about regioselectivity of hydrogen-bond self-assemble and cyclization reactions from light.
Four asymmetric hydrogen-bond acceptors of 1, 4-bis[2-(4-pyridyl) ethenyl]benzene derivatives with higher yields were synthesized through the classical Witting-Horner and Sonogashira cross-coupling reactions, and their structures and spectral properties were investigated. The series of compounds all have been characterized by NMR, MS and element analysis. Crystal structures indicated that the conformation of hydrogen-bond self-assemble may be change due to the hindrance effect from the arylacetyl group in o-position of benzene. UV-Vis spectra combined with time-dependent density functional theory (TDDFT) calculation results showed that target compounds all display a strong π→π* and ICT transition absorptions. Fluorescence spectrum indicated that gradual increasing of conjugate systems make their emission peak tend to a red shift, which is conducive to π-π accumulation. Above results will provide certain synthetic basis and theoretical foundation for subsequent studies about regioselectivity of hydrogen-bond self-assemble and cyclization reactions from light.
2017, 37(2): 403-410
doi: 10.6023/cjoc201607029
Abstract:
A series of novel strobilurin derivatives containing 1, 3, 4-oxdiazole moity were designed and synthesized based on the bioisosterism and coordination of active substructure theories. The structures of new compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. The bioassay indicated that the fungicidal activities of some compounds against Sclerotinia sclerotiorum reached the activity of azoxystrobin as the control and some compounds against Rhizotonia cerealis in vitro were more effective than the same control. Their structure-activity relationship was discussed. Methyl (E)-2-(2-((4-(1, 3, 4-oxadiazol-2-yl) phenoxy) methyl) phenyl)-3-methoxyacrylate (Ⅱa) and methyl (E)-2-(2-((4-(5-ethyl-1, 3, 4-oxadiazol-2-yl) phe-noxy) methyl) phenyl)-3-methoxyacrylate (Ⅱc) could be considered as leading compounds for further investigation.
A series of novel strobilurin derivatives containing 1, 3, 4-oxdiazole moity were designed and synthesized based on the bioisosterism and coordination of active substructure theories. The structures of new compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. The bioassay indicated that the fungicidal activities of some compounds against Sclerotinia sclerotiorum reached the activity of azoxystrobin as the control and some compounds against Rhizotonia cerealis in vitro were more effective than the same control. Their structure-activity relationship was discussed. Methyl (E)-2-(2-((4-(1, 3, 4-oxadiazol-2-yl) phenoxy) methyl) phenyl)-3-methoxyacrylate (Ⅱa) and methyl (E)-2-(2-((4-(5-ethyl-1, 3, 4-oxadiazol-2-yl) phe-noxy) methyl) phenyl)-3-methoxyacrylate (Ⅱc) could be considered as leading compounds for further investigation.
2017, 37(2): 411-417
doi: 10.6023/cjoc201609013
Abstract:
A clean, economical and efficient approach to phenylcarbamates and methylene diphenyl dicarbamates was reported. With cheap and easily available nonmetal selenium as the catalyst, carbon monoxide instead of virulent phosgene as the carbonylation reagent, oxygen as the oxidant, the selenium-catalyzed oxidative carbonylation reaction of aniline could proceed smoothly with alcohols to afford phenylcarbamates mostly in moderate to good yields. Then, catalyzed by HCl/ZnCl2, the condensation of formaldehyde with the generated phenylcarbamates gave methylene diphenyl dicarbamates in moderate to good yields. The applicability of the substrates was good. Catalyst selenium could be easily recovered due to its function of phase-transfer catalysis and could be recycled. High atomic economy, low cost, no emission of corrosive waste, and phosgene-free condition make this approach very promising. The possible reaction mechanisms were also proposed.
A clean, economical and efficient approach to phenylcarbamates and methylene diphenyl dicarbamates was reported. With cheap and easily available nonmetal selenium as the catalyst, carbon monoxide instead of virulent phosgene as the carbonylation reagent, oxygen as the oxidant, the selenium-catalyzed oxidative carbonylation reaction of aniline could proceed smoothly with alcohols to afford phenylcarbamates mostly in moderate to good yields. Then, catalyzed by HCl/ZnCl2, the condensation of formaldehyde with the generated phenylcarbamates gave methylene diphenyl dicarbamates in moderate to good yields. The applicability of the substrates was good. Catalyst selenium could be easily recovered due to its function of phase-transfer catalysis and could be recycled. High atomic economy, low cost, no emission of corrosive waste, and phosgene-free condition make this approach very promising. The possible reaction mechanisms were also proposed.
2017, 37(2): 418-422
doi: 10.6023/cjoc201607032
Abstract:
Terminal alkynes are important building blocks in organic synthesis. Acetone protected terminal alkynes are frequently used in alkyne synthesis and reactions, which could be easily prepared by Pd-catalyzed Sonogashira cross-coupling reactions between electrophiles and 2-methyl-3-butyn-2-ol. At present, the deprotection of the acetone protected terminal alkynes is generally carried out in reflux toluene in the presence of potassium hydroxide for hours. However, this procedure suffers from the harsh reaction conditions and its application has been limited. Here in the deprotection of acetones has been discussed, and various solvent, temperature, substrates were investigated to advance the procedure, and it is found that by employing 1, 4-dioxane as solvent, this process can undergo smoothly at 60℃ with satisfying yields in 0.5~2 h in the presence of 2.0 equiv. KOH.
Terminal alkynes are important building blocks in organic synthesis. Acetone protected terminal alkynes are frequently used in alkyne synthesis and reactions, which could be easily prepared by Pd-catalyzed Sonogashira cross-coupling reactions between electrophiles and 2-methyl-3-butyn-2-ol. At present, the deprotection of the acetone protected terminal alkynes is generally carried out in reflux toluene in the presence of potassium hydroxide for hours. However, this procedure suffers from the harsh reaction conditions and its application has been limited. Here in the deprotection of acetones has been discussed, and various solvent, temperature, substrates were investigated to advance the procedure, and it is found that by employing 1, 4-dioxane as solvent, this process can undergo smoothly at 60℃ with satisfying yields in 0.5~2 h in the presence of 2.0 equiv. KOH.
2017, 37(2): 423-428
doi: 10.6023/cjoc201608003
Abstract:
A new benzothiazole-derived fluorescence probe 2-(4-azidobenzyl) oxy-3-(benzo[d]thiazol-2-yl)-5-methylben-zaldehyde (HBTA) was synthesized from 3-(benzo[d]thiazol-2-yl)-2-hydroxy-5-methylbenzaldehyde, and the structure of HBTA was characterized. The recognition behaviors of HBTA to H2S were investigated and the results show that HBTA exhibits good selectivity and sensitivity to H2S with fast response and good anti-interference ability. The probe can be applied to detect H2S in a broad pH range, and the detection limit of HBTA for H2S was estimated to be 9.09×10-7 mol·L-1. Cell imaging studies reveal that HBTA is capable of detect H2S in live cells.
A new benzothiazole-derived fluorescence probe 2-(4-azidobenzyl) oxy-3-(benzo[d]thiazol-2-yl)-5-methylben-zaldehyde (HBTA) was synthesized from 3-(benzo[d]thiazol-2-yl)-2-hydroxy-5-methylbenzaldehyde, and the structure of HBTA was characterized. The recognition behaviors of HBTA to H2S were investigated and the results show that HBTA exhibits good selectivity and sensitivity to H2S with fast response and good anti-interference ability. The probe can be applied to detect H2S in a broad pH range, and the detection limit of HBTA for H2S was estimated to be 9.09×10-7 mol·L-1. Cell imaging studies reveal that HBTA is capable of detect H2S in live cells.
2017, 37(2): 429-439
doi: 10.6023/cjoc201608024
Abstract:
A series of novel quinazolin-4(3H)-one derivatives 3a~3e and 4a possessing 3, 4-benzo[c]coumarin and amino side chain were designed and synthesized by the condensation reaction of 2-aminobenzamide and 3, 4-benzo[c] coumarin aldehyde prepared by Heck coupling reaction, followed by SN2 substitution reaction with haloalkane. The compounds were evaluated for their anti proliferation activities against four tumor cells and antimicrobial activities. The results showed that 3e showed moderate anti Hela activity with the IC50 value of 22.63 and 23.35 μmol/L for 4a against MCF-7. Most tested compounds exhibited significant anti Escherichia coli activities, and the inhibition rate was above 89% at the concentration of 50 μg/mL. The inhibition rates of 2-phenyl-4-(2-(piperidin-1-yl) ethoxy) quinazoline (1b) against Fusarium oxysporum and Rhizoctonia solani and 3d against Verticillium dahliae are 100%.
A series of novel quinazolin-4(3H)-one derivatives 3a~3e and 4a possessing 3, 4-benzo[c]coumarin and amino side chain were designed and synthesized by the condensation reaction of 2-aminobenzamide and 3, 4-benzo[c] coumarin aldehyde prepared by Heck coupling reaction, followed by SN2 substitution reaction with haloalkane. The compounds were evaluated for their anti proliferation activities against four tumor cells and antimicrobial activities. The results showed that 3e showed moderate anti Hela activity with the IC50 value of 22.63 and 23.35 μmol/L for 4a against MCF-7. Most tested compounds exhibited significant anti Escherichia coli activities, and the inhibition rate was above 89% at the concentration of 50 μg/mL. The inhibition rates of 2-phenyl-4-(2-(piperidin-1-yl) ethoxy) quinazoline (1b) against Fusarium oxysporum and Rhizoctonia solani and 3d against Verticillium dahliae are 100%.
2017, 37(2): 440-454
doi: 10.6023/cjoc201607024
Abstract:
Six kinds, twenty-two novel target molecules were first designed and synthesized by using substituted 1, 3-selenazole as a template, which were modified by 1, 2, 4-triazole, tetrazole, oxadiazole, pyrazole, 1, 2, 4-triazine and succinic imide respectively. Their structures were confirmed by IR, NMR and HRMS. The inhibitory activities of the target molecules against cell division cycle 25B phosphatase (Cdc25B) were evaluated. As a result, thirteen compounds exhibited good inhibitory activities. The IC50 values of five compounds were lower than the positive reference Na3VO4 and were expected to be anticancer drugs leading compounds. The analysis of structure-activity relationship found that the introduction of multinitrgon-heterocyclic triazole, tetrazole and triazine, thiadiazole and oxadiazole containing amino or mercapto group onto 1, 3-selenazole were expected to obtain novel excellent bioactivity organic selenium containing molecules.
Six kinds, twenty-two novel target molecules were first designed and synthesized by using substituted 1, 3-selenazole as a template, which were modified by 1, 2, 4-triazole, tetrazole, oxadiazole, pyrazole, 1, 2, 4-triazine and succinic imide respectively. Their structures were confirmed by IR, NMR and HRMS. The inhibitory activities of the target molecules against cell division cycle 25B phosphatase (Cdc25B) were evaluated. As a result, thirteen compounds exhibited good inhibitory activities. The IC50 values of five compounds were lower than the positive reference Na3VO4 and were expected to be anticancer drugs leading compounds. The analysis of structure-activity relationship found that the introduction of multinitrgon-heterocyclic triazole, tetrazole and triazine, thiadiazole and oxadiazole containing amino or mercapto group onto 1, 3-selenazole were expected to obtain novel excellent bioactivity organic selenium containing molecules.
2017, 37(2): 455-461
doi: 10.6023/cjoc201607045
Abstract:
A series of novel C-2 and N-3 disubstituted quinazolin-4(3H)-one derivatives 5 possessing amino acid chain were synthesized by the addition reaction of imine with iminoketene and aromatization using anthranilic acid, aromatic aldehyde and glycine ethyl ester as starting materials. After elimination of carboxymethyl in the acidic condition, novel quinazolin-4(3H)-one derivatives 9 bearing amino side chain were designed and synthesized by SN2 substitution reaction. The compounds were evaluated for their anti-proliferation activities against four tumor cells. The results showed that some of the compounds, such as 9ba and 9bc showed significantly anti Hela activity with the IC50 values of 8.16 μM and 7.47 μM, respectively, while 9bc and 9bd against A549 with the IC50 values of 5.62 μM and 9.54 μM, respectively. Structure activity relationship analysis of these analogues suggested that coumarin substituent (extended π planar aromatic ring) on C-2 position and the introduction of amino side chain should be favorable to their anti-tumor activities.
A series of novel C-2 and N-3 disubstituted quinazolin-4(3H)-one derivatives 5 possessing amino acid chain were synthesized by the addition reaction of imine with iminoketene and aromatization using anthranilic acid, aromatic aldehyde and glycine ethyl ester as starting materials. After elimination of carboxymethyl in the acidic condition, novel quinazolin-4(3H)-one derivatives 9 bearing amino side chain were designed and synthesized by SN2 substitution reaction. The compounds were evaluated for their anti-proliferation activities against four tumor cells. The results showed that some of the compounds, such as 9ba and 9bc showed significantly anti Hela activity with the IC50 values of 8.16 μM and 7.47 μM, respectively, while 9bc and 9bd against A549 with the IC50 values of 5.62 μM and 9.54 μM, respectively. Structure activity relationship analysis of these analogues suggested that coumarin substituent (extended π planar aromatic ring) on C-2 position and the introduction of amino side chain should be favorable to their anti-tumor activities.
2017, 37(2): 462-473
doi: 10.6023/cjoc201604059
Abstract:
Using (ethyl 4-methyl-2-(thiazol-2-yl)-1H-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate) (A) as a model compound, thirty 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives 2~6 were synthesized by nucleophilic addition reaction, elimination reaction and cyclization reaction. The structures of these new compounds were characterized by 1H NMR, 13C NMR, IR, MS and elemental analysis. The antibacterial activities of those compounds were screened using the disk diffusion method against C. neoformans, C. neoformans clinical isolates, C. albicans, E. coli and S. aureus. The bioactive assay results revealed that most of the 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains. In particular, some compounds exhibited excellent antimicrobial activities against the test microorganism MS except E. coli, and exhibited better antimicrobial activity against fungi than against bacteria. Furthermore, ethyl 4-ethyl-8-methyl-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate (4b) and ethyl 4-ethyl-8-fluoro-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzo-diazepine-3-carboxylate (4c), which had good antibacterial activities, were subjected to further pharmacological evaluation, including minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC) against C. neoformans, C. albicans, and S. aureus. The results showed that the MIC and MFC against C. albicans values for above compounds were much lower than those of fluconazole. A further study of the structure-activity rela-tionship revealed that the thiazole ring at C-2, the methyl, ethyl at C-4 and the methyl at C-8 are essential for antibacterial activity.
Using (ethyl 4-methyl-2-(thiazol-2-yl)-1H-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate) (A) as a model compound, thirty 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives 2~6 were synthesized by nucleophilic addition reaction, elimination reaction and cyclization reaction. The structures of these new compounds were characterized by 1H NMR, 13C NMR, IR, MS and elemental analysis. The antibacterial activities of those compounds were screened using the disk diffusion method against C. neoformans, C. neoformans clinical isolates, C. albicans, E. coli and S. aureus. The bioactive assay results revealed that most of the 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains. In particular, some compounds exhibited excellent antimicrobial activities against the test microorganism MS except E. coli, and exhibited better antimicrobial activity against fungi than against bacteria. Furthermore, ethyl 4-ethyl-8-methyl-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate (4b) and ethyl 4-ethyl-8-fluoro-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzo-diazepine-3-carboxylate (4c), which had good antibacterial activities, were subjected to further pharmacological evaluation, including minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC) against C. neoformans, C. albicans, and S. aureus. The results showed that the MIC and MFC against C. albicans values for above compounds were much lower than those of fluconazole. A further study of the structure-activity rela-tionship revealed that the thiazole ring at C-2, the methyl, ethyl at C-4 and the methyl at C-8 are essential for antibacterial activity.
2017, 37(2): 474-479
doi: 10.6023/cjoc201605042
Abstract:
A novel [1+1] Schiff base macrocyclic compound 3 has been synthesized from the reaction of precursors 1, 3-bis (3-amino-phenyl)-urea (1) with 1, 3-bis (2-formylphenoxy)-2-propa-nol (2). The macrocycle 3 was characterized by 1H NMR, FT-IR, FABMS spectra and elemental analysis, and the crystal structure of 3 was determined by X-ray diffraction analy-sis. The results show that the macrocycle 3 displays a selective recognition ability for AcO- ion by the coordination reaction of 3 with a series of anions using UV-vis absorption spectra technique. Furthermore, the coordination reaction of 3 with AcO- ion was investigated via UV-Vis spectra, 1H NMR and the isothermal titration calorimeter (ITC) respectively. The stoichiometric ratio, the association constant (K) and the thermodynamic parameters (ΔrHm, ΔrSm and ΔrGm) of the coordination reaction were obtained.
A novel [1+1] Schiff base macrocyclic compound 3 has been synthesized from the reaction of precursors 1, 3-bis (3-amino-phenyl)-urea (1) with 1, 3-bis (2-formylphenoxy)-2-propa-nol (2). The macrocycle 3 was characterized by 1H NMR, FT-IR, FABMS spectra and elemental analysis, and the crystal structure of 3 was determined by X-ray diffraction analy-sis. The results show that the macrocycle 3 displays a selective recognition ability for AcO- ion by the coordination reaction of 3 with a series of anions using UV-vis absorption spectra technique. Furthermore, the coordination reaction of 3 with AcO- ion was investigated via UV-Vis spectra, 1H NMR and the isothermal titration calorimeter (ITC) respectively. The stoichiometric ratio, the association constant (K) and the thermodynamic parameters (ΔrHm, ΔrSm and ΔrGm) of the coordination reaction were obtained.
2017, 37(2): 480-484
doi: 10.6023/cjoc201607019
Abstract:
A metal-free method for the preparation of thiocyanates through Na2S2O8/DBU (1, 8-diazabicyclo[5.4.0]undec-7-ene)-promoted direct thiocyanation of thiols with NaCN was developed. The reaction was run under mild conditions, and the products were obtained in 31%~78% yields.
A metal-free method for the preparation of thiocyanates through Na2S2O8/DBU (1, 8-diazabicyclo[5.4.0]undec-7-ene)-promoted direct thiocyanation of thiols with NaCN was developed. The reaction was run under mild conditions, and the products were obtained in 31%~78% yields.
2017, 37(2): 485-495
doi: 10.6023/cjoc201607030
Abstract:
A series of new 3, 6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions.The structures of the intermediates 3, 4, 6 and the target compounds 7 were characterized by 1H NMR, IR spectra and elemental analysis.All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B).The results show that some of them display significant inhibitory activities against Cdc25B and PTP1B.Among them, compound 7d exhibits the highest inhibitory activity against Cdc25B [IC50=(7.72±0.73)μg/mL]and 7u exhibits the highest inhibitory activity against PTP1B[IC50=(3.31±0.57)μg/mL].It is noteworthy that compounds 7b, 7d, 7l, 7t and 7u show higher inhibitory activities against Cdc25B and PTP1B.They can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
A series of new 3, 6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions.The structures of the intermediates 3, 4, 6 and the target compounds 7 were characterized by 1H NMR, IR spectra and elemental analysis.All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B).The results show that some of them display significant inhibitory activities against Cdc25B and PTP1B.Among them, compound 7d exhibits the highest inhibitory activity against Cdc25B [IC50=(7.72±0.73)μg/mL]and 7u exhibits the highest inhibitory activity against PTP1B[IC50=(3.31±0.57)μg/mL].It is noteworthy that compounds 7b, 7d, 7l, 7t and 7u show higher inhibitory activities against Cdc25B and PTP1B.They can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
2017, 37(2): 496-502
doi: 10.6023/cjoc201604033
Abstract:
Fouteen 2-methyl-3-ethylcarboxy-5-aryl-3a, 6a-dihydro-4, 6-dioxopyrrolino[3', 4'-d]-isoxazoliniumtetrachloro-ferrate derivatives 2a~2g and 2-methyl-3-carboxyl-5-aryl-3a, 6a-dihydro-4, 6-dioxopyrrolino[3', 4'-d]-isoxazolinium-tetra-chloroferrate derivatives 4a~4g were synthesized by using dimethylsulfate as a N-methylating reagent and ferric (III)-chloride as anion exchange reagent in hydrochloric acid. The structures of the target compounds 2 and 4 were characterized by 1H NMR, IR spectra and elemental analysis. The preliminary in vitro anticancer activity on the compounds showed that most compounds possess anti-cancer activity at some extent. At the test concentration of 20 μg/mL, compounds 2a~2g and 4a~4g showed inhibition activities in the range of 97.32%~99.94% and 97.45%~99.92% against cell division cycle 25B phosphatase (Cdc25B), respectively. At the test concentration of 20 μg/mL, compounds 2a~2g and 4d~4g showed inhibition activities in the range of 52.18%~97.15% and 86.66%~99.45% against SH2-containing protein tyrosine phosphatase-1 (SHP1), respectively. Compounds 4a~4c only have the inhibition activities in the range of 15.21%~47.11%, which is lower than IC50 against SHP1. Preliminary discussion was carried out on the structure-activity relationship of the target compounds.
Fouteen 2-methyl-3-ethylcarboxy-5-aryl-3a, 6a-dihydro-4, 6-dioxopyrrolino[3', 4'-d]-isoxazoliniumtetrachloro-ferrate derivatives 2a~2g and 2-methyl-3-carboxyl-5-aryl-3a, 6a-dihydro-4, 6-dioxopyrrolino[3', 4'-d]-isoxazolinium-tetra-chloroferrate derivatives 4a~4g were synthesized by using dimethylsulfate as a N-methylating reagent and ferric (III)-chloride as anion exchange reagent in hydrochloric acid. The structures of the target compounds 2 and 4 were characterized by 1H NMR, IR spectra and elemental analysis. The preliminary in vitro anticancer activity on the compounds showed that most compounds possess anti-cancer activity at some extent. At the test concentration of 20 μg/mL, compounds 2a~2g and 4a~4g showed inhibition activities in the range of 97.32%~99.94% and 97.45%~99.92% against cell division cycle 25B phosphatase (Cdc25B), respectively. At the test concentration of 20 μg/mL, compounds 2a~2g and 4d~4g showed inhibition activities in the range of 52.18%~97.15% and 86.66%~99.45% against SH2-containing protein tyrosine phosphatase-1 (SHP1), respectively. Compounds 4a~4c only have the inhibition activities in the range of 15.21%~47.11%, which is lower than IC50 against SHP1. Preliminary discussion was carried out on the structure-activity relationship of the target compounds.
2017, 37(2): 503-507
doi: 10.6023/cjoc201612005
Abstract:
The berberine chloride was synthesized starting from benzo[d][1, 3]dioxole with the mild condition and the simple operation in overall 33% yield. The route includes the five steps of nucleophilic ring opening, deprotection and cyclization and so on. All intermediates were determined by 1H NMR, 13C NMR and MS techniques.
The berberine chloride was synthesized starting from benzo[d][1, 3]dioxole with the mild condition and the simple operation in overall 33% yield. The route includes the five steps of nucleophilic ring opening, deprotection and cyclization and so on. All intermediates were determined by 1H NMR, 13C NMR and MS techniques.
2017, 37(2): 508-513
doi: 10.6023/cjoc201608017
Abstract:
A rapid and efficient ultrasound-assisted method for the synthesis of 2-thioxo-2H-thiopyran and 2-amino-6-thioxodihydropyridine derivatives by the reaction of 2-(1-phenylethylidene) malononitrile and carbon disulfide or isothiocy-anatobenzene catalyzed by NaOH has been developed. This protocol has the advantages of simple operation, short reaction times, high yields, and environmental friendliness. The structures of all the products were characterized by 1H NMR, 13C NMR, IR and MS techniques. The reported method is the efficient approach for the synthesis of 2-thioxo-2H-thiopyran and 2-amino-6-thi-oxodihydropyridine derivatives.
A rapid and efficient ultrasound-assisted method for the synthesis of 2-thioxo-2H-thiopyran and 2-amino-6-thioxodihydropyridine derivatives by the reaction of 2-(1-phenylethylidene) malononitrile and carbon disulfide or isothiocy-anatobenzene catalyzed by NaOH has been developed. This protocol has the advantages of simple operation, short reaction times, high yields, and environmental friendliness. The structures of all the products were characterized by 1H NMR, 13C NMR, IR and MS techniques. The reported method is the efficient approach for the synthesis of 2-thioxo-2H-thiopyran and 2-amino-6-thi-oxodihydropyridine derivatives.
2017, 37(2): 514-519
doi: 10.6023/cjoc201606030
Abstract:
The catalytic property of some hydrolases for the cyclocondensation of aldehydes with 2-aminobenzamide was researched in alcohol solvent, and pepsin was selected as the best catalyst. The reaction conditions were optimized through investigating the temperature, the enzyme loading, the ratio of substrates and the reaction time. Under the optimal conditions, 5 mg of pepsin could catalyze the cyclizing reaction of aldehydes with 2-aminobenzamide, and the corresponding 2, 3-dihydroquinazolin-4(1H)-ones were successfully obtained in high yields.
The catalytic property of some hydrolases for the cyclocondensation of aldehydes with 2-aminobenzamide was researched in alcohol solvent, and pepsin was selected as the best catalyst. The reaction conditions were optimized through investigating the temperature, the enzyme loading, the ratio of substrates and the reaction time. Under the optimal conditions, 5 mg of pepsin could catalyze the cyclizing reaction of aldehydes with 2-aminobenzamide, and the corresponding 2, 3-dihydroquinazolin-4(1H)-ones were successfully obtained in high yields.
2017, 37(2): 520-525
doi: 10.6023/cjoc201607044
Abstract:
To study chemical constituents in the ethanol extract of Paliurus ramosissimus (Lour.) Poir, two new compounds along with four known compounds were isolated and purified by repeated gel column chromatographies and high performance preparative liquid chromatography. On the basis of spectroscopic methods (HR-ESIMS, 1D-and 2D-NMR), their structures were identified as 2α-(cis-p-hydroxy-cinnamyloxy)-3α-hydroxy-27-(trans-p-hydroxy-cinnamyloxy) betulinic acid (1), 2α-(trans-p-hydroxy-cinnamyloxy)-3α-hydroxy-27-(cis-p-hydroxy-cinnamyloxy) betulinic acid (2), messagenic acid A (3), mes-sagenic acid B (4), betulinaldehyde (5) and β-sitosterol (6). Among them, compounds 1 and 2 were new compounds named as paliurusene A and paliurusene B, which belong to triterpenoids, compounds 3~6 were isolated from this plant for the first time. The anti-tumor activity of compounds 1~3 was evaluated by methyl thiazolyl tetrazolium (MTT) assays. The result showed that compounds 1~3 presented obvious cytotoxicity in vitro against the cancer cell lines.
To study chemical constituents in the ethanol extract of Paliurus ramosissimus (Lour.) Poir, two new compounds along with four known compounds were isolated and purified by repeated gel column chromatographies and high performance preparative liquid chromatography. On the basis of spectroscopic methods (HR-ESIMS, 1D-and 2D-NMR), their structures were identified as 2α-(cis-p-hydroxy-cinnamyloxy)-3α-hydroxy-27-(trans-p-hydroxy-cinnamyloxy) betulinic acid (1), 2α-(trans-p-hydroxy-cinnamyloxy)-3α-hydroxy-27-(cis-p-hydroxy-cinnamyloxy) betulinic acid (2), messagenic acid A (3), mes-sagenic acid B (4), betulinaldehyde (5) and β-sitosterol (6). Among them, compounds 1 and 2 were new compounds named as paliurusene A and paliurusene B, which belong to triterpenoids, compounds 3~6 were isolated from this plant for the first time. The anti-tumor activity of compounds 1~3 was evaluated by methyl thiazolyl tetrazolium (MTT) assays. The result showed that compounds 1~3 presented obvious cytotoxicity in vitro against the cancer cell lines.
2017, 37(2): 526-532
doi: 10.6023/cjoc201608018
Abstract:
Aryloxyphenoxypropionates (APPs) are a class of herbicides targeting on acetyl-coenzyme A carboxylase (ACCase) in monocot chloroplast. The article presents synthesis of twenty three novel ethyl 2-(4-(pyridin-2-yl-oxy) phenylamino)-propanoates/acetates, and their structures were characterized by 1H NMR, HRMS and X-ray single-crystal diffraction. The herbicidal activities on barnyard grass and rape of the novel compounds were evaluated. Ethyl 2-(4-(5-nitropyridin-2-yloxy)-phenylamino) propanoate (B5) showed almost the same level of herbicidal activity on barnyard grass as commercial herbicide fluazifop-methyl which could become a potential lead compound on weeds.
Aryloxyphenoxypropionates (APPs) are a class of herbicides targeting on acetyl-coenzyme A carboxylase (ACCase) in monocot chloroplast. The article presents synthesis of twenty three novel ethyl 2-(4-(pyridin-2-yl-oxy) phenylamino)-propanoates/acetates, and their structures were characterized by 1H NMR, HRMS and X-ray single-crystal diffraction. The herbicidal activities on barnyard grass and rape of the novel compounds were evaluated. Ethyl 2-(4-(5-nitropyridin-2-yloxy)-phenylamino) propanoate (B5) showed almost the same level of herbicidal activity on barnyard grass as commercial herbicide fluazifop-methyl which could become a potential lead compound on weeds.
2017, 37(2): 533-540
doi: 10.6023/cjoc201608023
Abstract:
A novel series of 3-aryl pyridazinone was proposed on the base of structure activity relationships of diverse protoporphyrinogen oxidase inhibitors. Synthetic method of 3-aryl pyridazinones was investigated and 9 compounds were synthesized for interior screening test of herbicidal activity and crop safety. Bioassay results showed that most of 3-aryl-pyridazi-nones exhibit excellent pre-or post-emergence herbicidal activity. Herein, 3-(2, 4-dichloro-5-(cyclopentyloxy) phenyl)-1-methyl-6-(trifluoro methyl) pyridazin-4(1H)-one (Ie) with high activity was selected as a post-herbicide candidate into corn field trial. The results showed that Ie exhibited higher total effective rate against weeds at the dose of 60 g a.i./hm2 than mesotrione at 105 g a.i./hm2, and safety to corn after emergence as well.
A novel series of 3-aryl pyridazinone was proposed on the base of structure activity relationships of diverse protoporphyrinogen oxidase inhibitors. Synthetic method of 3-aryl pyridazinones was investigated and 9 compounds were synthesized for interior screening test of herbicidal activity and crop safety. Bioassay results showed that most of 3-aryl-pyridazi-nones exhibit excellent pre-or post-emergence herbicidal activity. Herein, 3-(2, 4-dichloro-5-(cyclopentyloxy) phenyl)-1-methyl-6-(trifluoro methyl) pyridazin-4(1H)-one (Ie) with high activity was selected as a post-herbicide candidate into corn field trial. The results showed that Ie exhibited higher total effective rate against weeds at the dose of 60 g a.i./hm2 than mesotrione at 105 g a.i./hm2, and safety to corn after emergence as well.
