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2020 Volume 40 Issue 9
2020, 40(9): 2607-2625
doi: 10.6023/cjoc202004042
Abstract:
As a representative hard Lewis acid, aluminum trichloride (AlCl3) has attracted more and more attention in the past decades. The reactions promoted via the activation of halogens, oxygen, nitrogen, sulfur compounds and π-bonds with AlCl3 are systematically reviewed, and some recent progress in last ten years is updated as well. Moreover, the new application fields of AlCl3 are prospected.
As a representative hard Lewis acid, aluminum trichloride (AlCl3) has attracted more and more attention in the past decades. The reactions promoted via the activation of halogens, oxygen, nitrogen, sulfur compounds and π-bonds with AlCl3 are systematically reviewed, and some recent progress in last ten years is updated as well. Moreover, the new application fields of AlCl3 are prospected.
2020, 40(9): 2626-2640
doi: 10.6023/cjoc202004002
Abstract:
Thieno[2, 3-d]pyrimidine compounds are an important class of organic synthesis intermediates and pharmacologically active molecules, which not only have broad medical application prospect, but also worth researching. Therefore the synthesis of them has attracted much attention. The previous methods mainly apply tandem cyclization or one-pot multi-com-ponent reaction combined with microwave-assisted reaction or new catalysts to reach the purpose of shortening reaction time, reducing steps, enhancing yields and lowering costs. In this paper, the recent progress in the synthesis of thieno[2, 3-d]pyri-midine compounds via tandem cyclization in recent ten years, especially in the latest five years, is reviewed. The problems and limitations faced are discussed, and the development directions are also prospected.
Thieno[2, 3-d]pyrimidine compounds are an important class of organic synthesis intermediates and pharmacologically active molecules, which not only have broad medical application prospect, but also worth researching. Therefore the synthesis of them has attracted much attention. The previous methods mainly apply tandem cyclization or one-pot multi-com-ponent reaction combined with microwave-assisted reaction or new catalysts to reach the purpose of shortening reaction time, reducing steps, enhancing yields and lowering costs. In this paper, the recent progress in the synthesis of thieno[2, 3-d]pyri-midine compounds via tandem cyclization in recent ten years, especially in the latest five years, is reviewed. The problems and limitations faced are discussed, and the development directions are also prospected.
2020, 40(9): 2641-2657
doi: 10.6023/cjoc202004005
Abstract:
Selectfluor, a commercial electrophilic fluorination reagent with superior performance, is widely used in fluorination reactions. In recent years, Selectfluor has also been widely applied as "fluorine-free" functional reagent in organic synthesis. Especially the application of Selectfluor/transition metals synergetic catalytic system has made great progress. However, this catalytic system has some disadvantages, such as the use of expensive transition metals and environmental unfriendliness. Therefore, more and more attention has been paid to the application of Selectfluor as "fluorine-free" functional reagent under transition metal-free conditions. In this paper, classified by the type of reactions, the research progress of Selectfluor as a "fluorine-free" functional reagent in organic synthesis under transition metal-free conditions is reviewed, and their future outlook is also discussed.
Selectfluor, a commercial electrophilic fluorination reagent with superior performance, is widely used in fluorination reactions. In recent years, Selectfluor has also been widely applied as "fluorine-free" functional reagent in organic synthesis. Especially the application of Selectfluor/transition metals synergetic catalytic system has made great progress. However, this catalytic system has some disadvantages, such as the use of expensive transition metals and environmental unfriendliness. Therefore, more and more attention has been paid to the application of Selectfluor as "fluorine-free" functional reagent under transition metal-free conditions. In this paper, classified by the type of reactions, the research progress of Selectfluor as a "fluorine-free" functional reagent in organic synthesis under transition metal-free conditions is reviewed, and their future outlook is also discussed.
2020, 40(9): 2658-2668
doi: 10.6023/cjoc202003060
Abstract:
Formic acid (HCOOH) has great potential as liquid hydrogen storage materials and for clean hydrogen production. In the past decade, researchers have not only made significant progress in developing more active, stable, and selective catalysts, but also proposed the concept of the reversible system of hydrogen release and storage. This review covers the latest progress of homogeneous catalysts in this field, focusing on the noble metal based catalysts represented by ruthenium, rhodium, and iridium, as well as the non-noble metal based catalysts such as iron, cobalt, nickel, copper, aluminum and so on. It is hoped that this review will provide some insights and idea for developing better catalytic systems for the dehydrogenation of formic acid in the future.
Formic acid (HCOOH) has great potential as liquid hydrogen storage materials and for clean hydrogen production. In the past decade, researchers have not only made significant progress in developing more active, stable, and selective catalysts, but also proposed the concept of the reversible system of hydrogen release and storage. This review covers the latest progress of homogeneous catalysts in this field, focusing on the noble metal based catalysts represented by ruthenium, rhodium, and iridium, as well as the non-noble metal based catalysts such as iron, cobalt, nickel, copper, aluminum and so on. It is hoped that this review will provide some insights and idea for developing better catalytic systems for the dehydrogenation of formic acid in the future.
2020, 40(9): 2669-2677
doi: 10.6023/cjoc202005013
Abstract:
Owing to the poor leaving character of hydroxy group, the efficient activation of allylic alcohols is important to allylic substitution reaction. In recent years, the efficient activation of allylic alcohols by non-typical acid activators and even no extra activators has been rapidly developed, and provides a novel approach to efficient activation of allylic alcohols. The recent developments in this area are summarized on the basis of different activation modes and mechanisms.
Owing to the poor leaving character of hydroxy group, the efficient activation of allylic alcohols is important to allylic substitution reaction. In recent years, the efficient activation of allylic alcohols by non-typical acid activators and even no extra activators has been rapidly developed, and provides a novel approach to efficient activation of allylic alcohols. The recent developments in this area are summarized on the basis of different activation modes and mechanisms.
2020, 40(9): 2678-2691
doi: 10.6023/cjoc202002033
Abstract:
In recent years, quinone imine ketals (QIKs) have been used as excellent organic synthons to the construction of complex organic molecules due to containing diverse functional groups (C=N, C=C and ketal etc.). Exploring the site-selectivity (chemo-, regio- and stereo-selectivity) of QIKs is not only a very significant research topic, but also a challenging research work. The preparation methods of QIKs and its applications in organic synthesis are reviewed according to the recent progress.
In recent years, quinone imine ketals (QIKs) have been used as excellent organic synthons to the construction of complex organic molecules due to containing diverse functional groups (C=N, C=C and ketal etc.). Exploring the site-selectivity (chemo-, regio- and stereo-selectivity) of QIKs is not only a very significant research topic, but also a challenging research work. The preparation methods of QIKs and its applications in organic synthesis are reviewed according to the recent progress.
2020, 40(9): 2692-2701
doi: 10.6023/cjoc202004017
Abstract:
Ethylene glycol (EG) is an important fundamental chemical material, which has been widely used in the production of industrial chemicals such as polyester. Catalytic hydrogenation of oxalate into EG is a key step in the "coal-to-EG" industrial route. Design of efficient catalysts for catalyzing the hydrogenation of oxalate esters is a research hotspot. The research progress of ruthenium catalysts with metal-ligand cooperation in the homogeneous catalytic hydrogenation of oxalate esters in the past decade is reviewed. Based on the relationship between the catalyst structures and properties, the catalytic hydrogenation mechanism is discussed, which provides a reference for the further design and development of new catalysts with excellent performance.
Ethylene glycol (EG) is an important fundamental chemical material, which has been widely used in the production of industrial chemicals such as polyester. Catalytic hydrogenation of oxalate into EG is a key step in the "coal-to-EG" industrial route. Design of efficient catalysts for catalyzing the hydrogenation of oxalate esters is a research hotspot. The research progress of ruthenium catalysts with metal-ligand cooperation in the homogeneous catalytic hydrogenation of oxalate esters in the past decade is reviewed. Based on the relationship between the catalyst structures and properties, the catalytic hydrogenation mechanism is discussed, which provides a reference for the further design and development of new catalysts with excellent performance.
2020, 40(9): 2702-2713
doi: 10.6023/cjoc202003064
Abstract:
As an important kind of heterocyclic molecules, mesoionic compounds are widely used in medicine, pesticide and other fields. Ever since they were discovered in 1935, mesoionic compounds have been extensively explored in terms of synthesis, properties and applications. Many references relating to these compounds have been published over years revealing their unique reactivity and bioactivity. An overview of mesoionic compounds from the perspectives of synthetic methods, reaction mechanisms and applications is offered. Their potentials as a dominant active structure for development of pesticides are also discussed.
As an important kind of heterocyclic molecules, mesoionic compounds are widely used in medicine, pesticide and other fields. Ever since they were discovered in 1935, mesoionic compounds have been extensively explored in terms of synthesis, properties and applications. Many references relating to these compounds have been published over years revealing their unique reactivity and bioactivity. An overview of mesoionic compounds from the perspectives of synthetic methods, reaction mechanisms and applications is offered. Their potentials as a dominant active structure for development of pesticides are also discussed.
2020, 40(9): 2714-2724
doi: 10.6023/cjoc202004034
Abstract:
Owing to the important physiological and pharmacological activities of benzofuran compounds, the exploration for efficient synthesis methods is of great value and wide application. Aurone-derived azadienes have been identified to be effective reactants in the field of organic synthesis owing to the driving force of aromatization. A large number of reactions based on 1, 4-conjugate addition and tandem cyclization have been reported, which exhibited great advantages in the construction of heterocycles with benzofuran skeletons. In this paper, the recent progress in the chemical transformations of aurone-derived azadienens is reviewed, with emphasis on the employed catalytic system and the plausible mechanism of some reactions.
Owing to the important physiological and pharmacological activities of benzofuran compounds, the exploration for efficient synthesis methods is of great value and wide application. Aurone-derived azadienes have been identified to be effective reactants in the field of organic synthesis owing to the driving force of aromatization. A large number of reactions based on 1, 4-conjugate addition and tandem cyclization have been reported, which exhibited great advantages in the construction of heterocycles with benzofuran skeletons. In this paper, the recent progress in the chemical transformations of aurone-derived azadienens is reviewed, with emphasis on the employed catalytic system and the plausible mechanism of some reactions.
2020, 40(9): 2725-2741
doi: 10.6023/cjoc202003054
Abstract:
Olefin metathesis has been one of the most important methods to construct carbon-carbon double bonds, which has been catalyzed by ruthenium carbene. Investigations in olefin metathesis have focused on stereoselective transformations in recent years. The research progress on the applications of stereoselective olefin metathesis reactions catalyzed by ruthenium carbene complexes is reviewed. The advancements in stereoselectivity of olefin metathesis are described in detail, and the categories and improvement of ruthenium catalysts are also introduced over the past decade. Finally, the future development for olefin metathesis is further evaluated as well.
Olefin metathesis has been one of the most important methods to construct carbon-carbon double bonds, which has been catalyzed by ruthenium carbene. Investigations in olefin metathesis have focused on stereoselective transformations in recent years. The research progress on the applications of stereoselective olefin metathesis reactions catalyzed by ruthenium carbene complexes is reviewed. The advancements in stereoselectivity of olefin metathesis are described in detail, and the categories and improvement of ruthenium catalysts are also introduced over the past decade. Finally, the future development for olefin metathesis is further evaluated as well.
2020, 40(9): 2742-2754
doi: 10.6023/cjoc202003056
Abstract:
Isoxazoline is an important class of heterocyclic ring with a wide range of biological characteristics, which is the key structural framework of many natural products and bioactive compounds. The effective synthetic method of isoxazoline has been the subject of extensive research. In this review, the latest progress in the synthesis of various functionalized isoxazoline by allyl oxime, involving the radical oxidation/cyclization reaction in the presence of oxidants is described. These reactions are usually carried out under neutral conditions using readily available oxidants and different metals or metal-free catalysis.
Isoxazoline is an important class of heterocyclic ring with a wide range of biological characteristics, which is the key structural framework of many natural products and bioactive compounds. The effective synthetic method of isoxazoline has been the subject of extensive research. In this review, the latest progress in the synthesis of various functionalized isoxazoline by allyl oxime, involving the radical oxidation/cyclization reaction in the presence of oxidants is described. These reactions are usually carried out under neutral conditions using readily available oxidants and different metals or metal-free catalysis.
2020, 40(9): 2755-2763
doi: 10.6023/cjoc202003068
Abstract:
Phathalocyanine metal complexes catalyzed oxidative condensation of 2-aminobenzyl alcohols with nitriles and ketones has been developed under air to afford quinazolines and quinolines, respectively. After systematic investigation, iron(Ⅱ) phathalocyanine displayed higher catalytic activity in quinazoline synthesis and copper(Ⅱ) phathalocyanine showed higher efficiency in quinoline preparation. Under the optimized conditions, various nitriles and ketones were well adaptted to give the corresponding products in good yields.
Phathalocyanine metal complexes catalyzed oxidative condensation of 2-aminobenzyl alcohols with nitriles and ketones has been developed under air to afford quinazolines and quinolines, respectively. After systematic investigation, iron(Ⅱ) phathalocyanine displayed higher catalytic activity in quinazoline synthesis and copper(Ⅱ) phathalocyanine showed higher efficiency in quinoline preparation. Under the optimized conditions, various nitriles and ketones were well adaptted to give the corresponding products in good yields.
2020, 40(9): 2788-2797
doi: 10.6023/cjoc202005031
Abstract:
In an effort to develop novel β-triketone herbicides containing a barbituric acid moiety, a series of 5-acylbarbituric acid derivatives were designed, synthesized, and tested for herbicidal activity. The bioassay results showed that some of the target compounds, such as 5-(2-(2-chloro-4-fluorophenoxy)-1-hydroxyethylidene)-1, 3-dimethylpyrimidine-2, 4, 6(1H, 3H, 5H)-trione (BBA-22) and 5-(2-(2-bromo-4-fluorophenoxy)-1-hydroxyethylidene)-1, 3-dimethylpyrimidine-2, 4, 6(1H, 3H, 5H)-trione (BBA-27), exhibited excellent herbicidal activity against all tested weeds at a dosage of 1500 g·ha-1. In particular, compound BBA-22 displayed good pre-emergent herbicidal activity against Brassica campestris, Amaranthus retroflexus and Digitaria sanguinalis even at a dosage of 187.5 g·ha-1, surpassing that of a commercial herbicide 2, 4-dichlorophenoxyacetic acid (2, 4-D). Investigation of the molecular mode of action of compound BBA-22 upon treatment of Arabidopsis thaliana as a model plant revealed that BBA-22 was degraded to the corresponding phenoxyacetic acid, which explains why the herbicidal mechanism is similar to that of auxin-type herbicides. The present study demonstrates that compound BBA-22 is a proherbicide of the corresponding phenoxyacetic acid auxin herbicide and a potential lead compound for further development of novel auxin herbicides.
In an effort to develop novel β-triketone herbicides containing a barbituric acid moiety, a series of 5-acylbarbituric acid derivatives were designed, synthesized, and tested for herbicidal activity. The bioassay results showed that some of the target compounds, such as 5-(2-(2-chloro-4-fluorophenoxy)-1-hydroxyethylidene)-1, 3-dimethylpyrimidine-2, 4, 6(1H, 3H, 5H)-trione (BBA-22) and 5-(2-(2-bromo-4-fluorophenoxy)-1-hydroxyethylidene)-1, 3-dimethylpyrimidine-2, 4, 6(1H, 3H, 5H)-trione (BBA-27), exhibited excellent herbicidal activity against all tested weeds at a dosage of 1500 g·ha-1. In particular, compound BBA-22 displayed good pre-emergent herbicidal activity against Brassica campestris, Amaranthus retroflexus and Digitaria sanguinalis even at a dosage of 187.5 g·ha-1, surpassing that of a commercial herbicide 2, 4-dichlorophenoxyacetic acid (2, 4-D). Investigation of the molecular mode of action of compound BBA-22 upon treatment of Arabidopsis thaliana as a model plant revealed that BBA-22 was degraded to the corresponding phenoxyacetic acid, which explains why the herbicidal mechanism is similar to that of auxin-type herbicides. The present study demonstrates that compound BBA-22 is a proherbicide of the corresponding phenoxyacetic acid auxin herbicide and a potential lead compound for further development of novel auxin herbicides.
2020, 40(9): 2798-2803
doi: 10.6023/cjoc202005084
Abstract:
Ethyl 5-formyl-3, 4-dimethyl-pyrrole-2-carboxylate and rhodamine B hydrazide were used to synthesize a rhodamine derivative R1. Notably, the as-synthesized R1 displayed great sensitivity and selectivity, which was utilized to be an off-on fluorescence probe for Cu2+ detectionin mediums that contained water. Besides, the Cu2+ ions limit of detection (LOD) was 0.201 μmol·L-1, and R1 was able to sense Cu2+ by "naked-eye" according to the change in color to pink from colorless. In addition, Cu2+ detection was assessed within the actual water samples for testing the probe actual application.
Ethyl 5-formyl-3, 4-dimethyl-pyrrole-2-carboxylate and rhodamine B hydrazide were used to synthesize a rhodamine derivative R1. Notably, the as-synthesized R1 displayed great sensitivity and selectivity, which was utilized to be an off-on fluorescence probe for Cu2+ detectionin mediums that contained water. Besides, the Cu2+ ions limit of detection (LOD) was 0.201 μmol·L-1, and R1 was able to sense Cu2+ by "naked-eye" according to the change in color to pink from colorless. In addition, Cu2+ detection was assessed within the actual water samples for testing the probe actual application.
2020, 40(9): 2804-2810
doi: 10.6023/cjoc202005081
Abstract:
In order to find efficient and low toxicity anti-tumor drugs, a series of novel quinazoline derivatives containing N-(3-aminophenyl)acrylamide were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines (H1975, PC-3, MGC-803) by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited better antiproliferative activities against the four human tumor cell lines. Among them, N-(3-(2-((4-((4-chlorophenyl)amino)-7-methoxy-quinazolin-6-yl)oxy)acetamido)phenyl)acrylamide (13j) showed the best antiproliferative activity against H1975 and MGC-803 cancer cell lines with IC50 values of (6.77±0.65) and (4.06±0.34) μmol/L, respectively. Its activity was better than the positive control gefitinib. In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.
In order to find efficient and low toxicity anti-tumor drugs, a series of novel quinazoline derivatives containing N-(3-aminophenyl)acrylamide were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines (H1975, PC-3, MGC-803) by using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most compounds exhibited better antiproliferative activities against the four human tumor cell lines. Among them, N-(3-(2-((4-((4-chlorophenyl)amino)-7-methoxy-quinazolin-6-yl)oxy)acetamido)phenyl)acrylamide (13j) showed the best antiproliferative activity against H1975 and MGC-803 cancer cell lines with IC50 values of (6.77±0.65) and (4.06±0.34) μmol/L, respectively. Its activity was better than the positive control gefitinib. In a nutshell, this work provides clues to discover antitumor agent based on the quinazoline scaffold.
2020, 40(9): 2811-2816
doi: 10.6023/cjoc202005060
Abstract:
Four new diterpenoids, casearoids A~D (1~4), including dolabrane, orosane, labdane, and cembrane, were isolated and characterized from Microdesmis casearifolia. Their structures were elucidated by extensive spectroscopic data analysis. The absolute configurations of these diterpenoids were established by analysis of the electronic circular dichroism (ECD) data.
Four new diterpenoids, casearoids A~D (1~4), including dolabrane, orosane, labdane, and cembrane, were isolated and characterized from Microdesmis casearifolia. Their structures were elucidated by extensive spectroscopic data analysis. The absolute configurations of these diterpenoids were established by analysis of the electronic circular dichroism (ECD) data.
2020, 40(9): 2817-2826
doi: 10.6023/cjoc202001017
Abstract:
In the present work, a simple and facile synthesis of a new series of 3-arylvinylquinoxaline-2-carboxylic acids has been achieved using the newly-synthesized ethyl 3-bromomethylquinoxaline-2-carboxylate as substrate through one-pot sequential Arbuzov/Horner-Wadsworth-Emmons (HWE)/ester hydrolysis reaction procedure. A primary in vitro evaluation for their inhibitory activity against Mycobacterium smegmatis (M. smegmatis) Leucyl-tRNA synthetase (Mtb LeuRS) revealed that (E)-3-(3-nitrostyryl)quinoxaline-2-carboxylic acid (5j) represented the most active compound in this round of effort with the IC50 value of 14.7 μmol·L-1, which was much superior to the reference drug AN2679, indicating the potential medicinal value for the exploration of novel Mtb LeuRS inhibitor. The results of molecular docking analyses using CDOCKER module of Discovery Studio (DS) software suggested that it could bind well to the active site of Mtb LeuRS. Moreover, the antitubercular assay against M. smegmatis also revealed that the nitro-substituted 5j has the best anti-tubercular activity with the minimum inhibitory concentration (MIC) value 15.6 μg/mL, being comparable with the reference rifampicin.
In the present work, a simple and facile synthesis of a new series of 3-arylvinylquinoxaline-2-carboxylic acids has been achieved using the newly-synthesized ethyl 3-bromomethylquinoxaline-2-carboxylate as substrate through one-pot sequential Arbuzov/Horner-Wadsworth-Emmons (HWE)/ester hydrolysis reaction procedure. A primary in vitro evaluation for their inhibitory activity against Mycobacterium smegmatis (M. smegmatis) Leucyl-tRNA synthetase (Mtb LeuRS) revealed that (E)-3-(3-nitrostyryl)quinoxaline-2-carboxylic acid (5j) represented the most active compound in this round of effort with the IC50 value of 14.7 μmol·L-1, which was much superior to the reference drug AN2679, indicating the potential medicinal value for the exploration of novel Mtb LeuRS inhibitor. The results of molecular docking analyses using CDOCKER module of Discovery Studio (DS) software suggested that it could bind well to the active site of Mtb LeuRS. Moreover, the antitubercular assay against M. smegmatis also revealed that the nitro-substituted 5j has the best anti-tubercular activity with the minimum inhibitory concentration (MIC) value 15.6 μg/mL, being comparable with the reference rifampicin.
2020, 40(9): 2827-2835
doi: 10.6023/cjoc202006006
Abstract:
Pepsin from porcine gastric mucosa has a non-natural ability to catalyze the cyclocondensation of aromatic amines and 2-aminobenzaldehyde. The corresponding tetrahydroquinazolines were obtained in good yields (41%~95%) in aqueous methanol solution. The catalytic activity of pepsin was evaluated by investigating solvent, temperature, enzyme loading, and substrate ratio in the enzyme-catalyzed reaction. Herein, a potential biocatalytic approach as an alternative to chemical synthesis for tetrahydroquinazoline derivatives was proposed.
Pepsin from porcine gastric mucosa has a non-natural ability to catalyze the cyclocondensation of aromatic amines and 2-aminobenzaldehyde. The corresponding tetrahydroquinazolines were obtained in good yields (41%~95%) in aqueous methanol solution. The catalytic activity of pepsin was evaluated by investigating solvent, temperature, enzyme loading, and substrate ratio in the enzyme-catalyzed reaction. Herein, a potential biocatalytic approach as an alternative to chemical synthesis for tetrahydroquinazoline derivatives was proposed.
2020, 40(9): 2845-2854
doi: 10.6023/cjoc202003062
Abstract:
In order to find more effective antitumor agents, a series of novel dehydroabietic acid derivatives bearing nitrate moiety were designed and synthesized. Their cytotoxicities were evaluated against human cancer cell lines of CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical) and BEL-7402 (liver), and human normal liver cell (HL-7702) and nasopharyngeal epithelial cell (NP69) using methyl thiazolyl tetrazolium (MTT) assay. Biological screening results demonstrated that most of the hybrids exhibited more potent cytotoxicity superior to parent compound dehydroabietic acid. Among them, 12-bromodehydroabietic acid-3'-nitrooxypropyl ester (5j) displayed better antiproliferative activity with IC50value of (8.36±0.14) μmol/L toward CNE-2 cells compared with cisplatin, and 2, 14-dinitrodehydroabietic acid-3'-nitrooxypropyl ester (5n) showed remarkable cytotoxicity with IC50 value of (11.23±0.21) μmol/L against BEL-7402 cells. Moreover, they exhibited lower cytotoxicity against human normal liver cell line HL-7702 and nasopharyngeal epithelial cell NP69. Besides, NO released amounts detection of all nitrates suggested that in most cases, the cytotoxicities were positively correlated with the levels of intracellular NO release in CNE-2 cells.
In order to find more effective antitumor agents, a series of novel dehydroabietic acid derivatives bearing nitrate moiety were designed and synthesized. Their cytotoxicities were evaluated against human cancer cell lines of CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical) and BEL-7402 (liver), and human normal liver cell (HL-7702) and nasopharyngeal epithelial cell (NP69) using methyl thiazolyl tetrazolium (MTT) assay. Biological screening results demonstrated that most of the hybrids exhibited more potent cytotoxicity superior to parent compound dehydroabietic acid. Among them, 12-bromodehydroabietic acid-3'-nitrooxypropyl ester (5j) displayed better antiproliferative activity with IC50value of (8.36±0.14) μmol/L toward CNE-2 cells compared with cisplatin, and 2, 14-dinitrodehydroabietic acid-3'-nitrooxypropyl ester (5n) showed remarkable cytotoxicity with IC50 value of (11.23±0.21) μmol/L against BEL-7402 cells. Moreover, they exhibited lower cytotoxicity against human normal liver cell line HL-7702 and nasopharyngeal epithelial cell NP69. Besides, NO released amounts detection of all nitrates suggested that in most cases, the cytotoxicities were positively correlated with the levels of intracellular NO release in CNE-2 cells.
2020, 40(9): 2855-2862
doi: 10.6023/cjoc202004051
Abstract:
An electrochemical selenylation/cyclization of N-allylthioamides has been developed for the synthesis of selenium-containing 2-thiazolines. This protocol provides an efficient approach to produce 2-thiazolines with broad substrate scope under mild reaction conditions. Preliminary mechanistic study indicates that selenium radical may be involved. The reaction is easy operated under catalyst- and oxidant-free conditions.
An electrochemical selenylation/cyclization of N-allylthioamides has been developed for the synthesis of selenium-containing 2-thiazolines. This protocol provides an efficient approach to produce 2-thiazolines with broad substrate scope under mild reaction conditions. Preliminary mechanistic study indicates that selenium radical may be involved. The reaction is easy operated under catalyst- and oxidant-free conditions.
2020, 40(9): 2863-2870
doi: 10.6023/cjoc202004048
Abstract:
An efficient and powerful approach for the construction of vinyl-substituted dihydroisoquinolone derivatives through ruthenium-catalyzed tandem C—H functionalization/annulation of imidates has been demonstrated. Various substituted functional groups of imidates could be well tolerated in this new transformation, delivering the corresponding products in moderate to good yields. This method represents the first successful example of Ru(Ⅱ)-catalyzed C—H functionalization/an-nulation of imidates with 4-vinyl-1, 3-dioxolan-2-one to the efficient synthesis of 3-vinyl-3, 4-dihydroisoquinolin-1(2H)-ones.
An efficient and powerful approach for the construction of vinyl-substituted dihydroisoquinolone derivatives through ruthenium-catalyzed tandem C—H functionalization/annulation of imidates has been demonstrated. Various substituted functional groups of imidates could be well tolerated in this new transformation, delivering the corresponding products in moderate to good yields. This method represents the first successful example of Ru(Ⅱ)-catalyzed C—H functionalization/an-nulation of imidates with 4-vinyl-1, 3-dioxolan-2-one to the efficient synthesis of 3-vinyl-3, 4-dihydroisoquinolin-1(2H)-ones.
2020, 40(9): 2895-2903
doi: 10.6023/cjoc202004054
Abstract:
Pyropheophorbide-a methyl ester was used as a starting material, and the chemical modification was carried out making use of its active groups attached to the chlorin periphery to establish the formyl group, ketene and α-diketone moieties around the N21-N23 axis. The nitrations or nitroalkylations at 3-, 12-, 20-position and on the exocyclic ring were performed by the electrophilic substitution on the aromatic macrocyclic chromophore, Henry reaction at the active carbonyl groups, and Michael addition to the β-keto ester and the ketene structures on the exocyclic ring as different donor-acceptor. A series of unreported nitro(nitroalkyl) substituted chlorins related to chlorophyll were synthesized and their chemical structures were characterized by elemental analysis, UV-Vis, IR and 1H NMR spectra.
Pyropheophorbide-a methyl ester was used as a starting material, and the chemical modification was carried out making use of its active groups attached to the chlorin periphery to establish the formyl group, ketene and α-diketone moieties around the N21-N23 axis. The nitrations or nitroalkylations at 3-, 12-, 20-position and on the exocyclic ring were performed by the electrophilic substitution on the aromatic macrocyclic chromophore, Henry reaction at the active carbonyl groups, and Michael addition to the β-keto ester and the ketene structures on the exocyclic ring as different donor-acceptor. A series of unreported nitro(nitroalkyl) substituted chlorins related to chlorophyll were synthesized and their chemical structures were characterized by elemental analysis, UV-Vis, IR and 1H NMR spectra.
2020, 40(9): 2904-2911
doi: 10.6023/cjoc202005037
Abstract:
An effective chemo- and enantioselective transfer hydrogenation of β, γ-alkynyl α-imino esters to prepare optically pure β, γ-alkynyl α-amino esters has been described. The excellent chemoselectivity was achieved by using chiral phosphoric acid catalyzed asymmetric reduction with benzothiazoline as hydride donor. The reaction exhibited good functional group tolerance, providing a range of optically active non-natural amino esters with excellent enantioselectivity.
An effective chemo- and enantioselective transfer hydrogenation of β, γ-alkynyl α-imino esters to prepare optically pure β, γ-alkynyl α-amino esters has been described. The excellent chemoselectivity was achieved by using chiral phosphoric acid catalyzed asymmetric reduction with benzothiazoline as hydride donor. The reaction exhibited good functional group tolerance, providing a range of optically active non-natural amino esters with excellent enantioselectivity.
2020, 40(9): 2938-2948
doi: 10.6023/cjoc202005010
Abstract:
A new zirconium(Ⅳ) metal-organic framework (Zr-MOF) based on tricarboxylate ligands, namely ZrL▪2H2O (L=2, 2', 2''-([1, 3, 5]-triazine-2, 4, 6-triimino)tribenzoic acid)) has been designed and synthesized. It can be served as a platform of multi-responsive fluorescence sensor for Fe3+ and Cr2O72- in water. The Stern-Volmer constants (KSV) are 9.54×104, 1.75×104 L·mol-1, and the limits of detection are 3.78×10-8, 9.12×10-7 mol/L, respectively. Meanwhile, it can also be used as a multi-response fluorescence probe to detect acetone, CCl4 and xylene in N, N-dimethylformamide (DMF) solution. The Stern-Volmer constants (KSV) are 6534.3, 4325.7, 4025.1 mL-1, and the limits of detection are 1.09×10-6, 2.73×10-5, 3.17×10-5 mL, respectively. The Zr-MOF was characterized by FTIR, 1H NMR, powder X-ray diffraction (PXRD), thermo gravimetric analysis (TGA) and elemental analysis. Interestingly, the Zr-MOF has the high water stability and pH stability, but its fluorescence intensity will show certain change law in the range of pH 0~14. Water and urine sample application test showed that Zr-MOF had high sensitive detection for Fe3+, and simulated organic solvents test showed that Zr-MOF has high sensitivity and selectivity to acetone, CCl4 and xylene.
A new zirconium(Ⅳ) metal-organic framework (Zr-MOF) based on tricarboxylate ligands, namely ZrL▪2H2O (L=2, 2', 2''-([1, 3, 5]-triazine-2, 4, 6-triimino)tribenzoic acid)) has been designed and synthesized. It can be served as a platform of multi-responsive fluorescence sensor for Fe3+ and Cr2O72- in water. The Stern-Volmer constants (KSV) are 9.54×104, 1.75×104 L·mol-1, and the limits of detection are 3.78×10-8, 9.12×10-7 mol/L, respectively. Meanwhile, it can also be used as a multi-response fluorescence probe to detect acetone, CCl4 and xylene in N, N-dimethylformamide (DMF) solution. The Stern-Volmer constants (KSV) are 6534.3, 4325.7, 4025.1 mL-1, and the limits of detection are 1.09×10-6, 2.73×10-5, 3.17×10-5 mL, respectively. The Zr-MOF was characterized by FTIR, 1H NMR, powder X-ray diffraction (PXRD), thermo gravimetric analysis (TGA) and elemental analysis. Interestingly, the Zr-MOF has the high water stability and pH stability, but its fluorescence intensity will show certain change law in the range of pH 0~14. Water and urine sample application test showed that Zr-MOF had high sensitive detection for Fe3+, and simulated organic solvents test showed that Zr-MOF has high sensitivity and selectivity to acetone, CCl4 and xylene.
2020, 40(9): 2764-2771
doi: 10.6023/cjoc202004033
Abstract:
Hydnocarpins are a rare type of flavonoligan compounds occurring in nature. Because of their rarity, only a few research has been devoted on their structural modification and activity. In this work, 23-iodo hydnocarpin D was synthesized from silibinin, which is cheap and commericially available. After azidation, reduction and amidation, 15 amido-derivatives of hydnocarpin D were obtained. These compounds with regard to their anticancer activities were evaluated on three kinds of human cancer cells, and the results showed that some compounds are active on A549 with IC50 values less than 10 μmol·L-1. 23-(3, 4-Dimethoxybenzamido)hydnocarpin D (6b) and 23-(2-chloro-4-fluorobenzamido)hydnocarpin D (6f) can strongly inhibit the growth of HeLa cells. 23-(4-Fluorobenzamido)hydnocarpin D (6g) and 23-[3, 5-bis(trifluoromethyl)benzamido]-hydnocarpin D (6m) showed potent activity against MCF-7 cells. These preliminary results testified that the synthsis of amido-derivative of hydnocarpin D could be an option for the development of new anti-cancer drug candidates.
Hydnocarpins are a rare type of flavonoligan compounds occurring in nature. Because of their rarity, only a few research has been devoted on their structural modification and activity. In this work, 23-iodo hydnocarpin D was synthesized from silibinin, which is cheap and commericially available. After azidation, reduction and amidation, 15 amido-derivatives of hydnocarpin D were obtained. These compounds with regard to their anticancer activities were evaluated on three kinds of human cancer cells, and the results showed that some compounds are active on A549 with IC50 values less than 10 μmol·L-1. 23-(3, 4-Dimethoxybenzamido)hydnocarpin D (6b) and 23-(2-chloro-4-fluorobenzamido)hydnocarpin D (6f) can strongly inhibit the growth of HeLa cells. 23-(4-Fluorobenzamido)hydnocarpin D (6g) and 23-[3, 5-bis(trifluoromethyl)benzamido]-hydnocarpin D (6m) showed potent activity against MCF-7 cells. These preliminary results testified that the synthsis of amido-derivative of hydnocarpin D could be an option for the development of new anti-cancer drug candidates.
2020, 40(9): 2772-2777
doi: 10.6023/cjoc202005073
Abstract:
A protocol for the synthesis of bibenzyls via nickel acetylacetonate-catalyzed coupling of arenes was devloped using di-tert-butylperoxide as the oxidant with the asistance of 1, 4-diazabicyclo[2.2.2]octane (DABCO). The process tolerated to different substrates, among of which, isopropylbenzene provided the most satisfactory yield of bibenzyls in 73% yield. The cross-coupling of arenes with cycloalkanes was also realized under the optimal reaction conditions but accompanied with the self-coupling of substrates. The method could effectively restrain the formation of alcohol, aldehyde, acid.
A protocol for the synthesis of bibenzyls via nickel acetylacetonate-catalyzed coupling of arenes was devloped using di-tert-butylperoxide as the oxidant with the asistance of 1, 4-diazabicyclo[2.2.2]octane (DABCO). The process tolerated to different substrates, among of which, isopropylbenzene provided the most satisfactory yield of bibenzyls in 73% yield. The cross-coupling of arenes with cycloalkanes was also realized under the optimal reaction conditions but accompanied with the self-coupling of substrates. The method could effectively restrain the formation of alcohol, aldehyde, acid.
2020, 40(9): 2778-2787
doi: 10.6023/cjoc202005051
Abstract:
Tryptophol derivatives are very important compounds with wide spectrum of pharmaceutical and physiological activity. Herein, the esterification reaction of trypthol and its derivatives with β, γ-unsaturated α-keto acids was reported by the use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBt) as conden-sation reagents. A series of β, γ-unsaturated α-keto trypanol ester derivatives were prepared in moderate to high yields. This method has advantages of riched functional group tolerance, readily available starting materials and easy operation.
Tryptophol derivatives are very important compounds with wide spectrum of pharmaceutical and physiological activity. Herein, the esterification reaction of trypthol and its derivatives with β, γ-unsaturated α-keto acids was reported by the use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBt) as conden-sation reagents. A series of β, γ-unsaturated α-keto trypanol ester derivatives were prepared in moderate to high yields. This method has advantages of riched functional group tolerance, readily available starting materials and easy operation.
2020, 40(9): 2836-2844
doi: 10.6023/cjoc202004013
Abstract:
Succinate dehydrogenase inhibitor is a low-toxic and high active fungicide. In order to develop novel and broad-spectrum succinate dehydrogenase inhibitor (SDHI) fungicides, thiophene was introduced into the structure of pyrazole carboxamide fungicides. Twenty four pyrazole-thiophene carboxamides were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS. The crystal structure of N-(4-methoxyphenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7i) was determined by X-ray diffraction. The antifungal activity of all the synthesized compounds was determined against six plant pathogenic fungi, and preliminary bioassays suggested that some compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium graminearum and Botrytis cinerea. Among them, N-(4-fluorophenethyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7c) exhibited the best antifungal activities against R. solani in vitro with EC50 value of 11.6 μmol/L, and N-(2-fluorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7j) against F. graminearum with EC50 value of 28.9 μmol/L. And N-(4-chlorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7h) showed similar inhibition abilities with thifluzamide against B. cinerea with EC50 value of 21.3 μmol/L. The molecular docking results showed that the high antifungal activitie compounds form stronger interactions with important amino acid residues of succinate dehydrogenase.
Succinate dehydrogenase inhibitor is a low-toxic and high active fungicide. In order to develop novel and broad-spectrum succinate dehydrogenase inhibitor (SDHI) fungicides, thiophene was introduced into the structure of pyrazole carboxamide fungicides. Twenty four pyrazole-thiophene carboxamides were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS. The crystal structure of N-(4-methoxyphenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7i) was determined by X-ray diffraction. The antifungal activity of all the synthesized compounds was determined against six plant pathogenic fungi, and preliminary bioassays suggested that some compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium graminearum and Botrytis cinerea. Among them, N-(4-fluorophenethyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7c) exhibited the best antifungal activities against R. solani in vitro with EC50 value of 11.6 μmol/L, and N-(2-fluorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7j) against F. graminearum with EC50 value of 28.9 μmol/L. And N-(4-chlorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7h) showed similar inhibition abilities with thifluzamide against B. cinerea with EC50 value of 21.3 μmol/L. The molecular docking results showed that the high antifungal activitie compounds form stronger interactions with important amino acid residues of succinate dehydrogenase.
2020, 40(9): 2871-2878
doi: 10.6023/cjoc202003047
Abstract:
Cyano compounds are a class of organic compounds with great value. Two different kinds of reactions have been reported using acetone cyanohydrin as reagent and substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole as substrate. The reaction pathway depends on the basic catalysts used when aromatic substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole was used as the substrate. Michael addition reaction occurred in the presence of MgBu2 with the product yield up to 95%, while alcoholysis reaction of amide occurred in the presence of 1, 1, 3, 3-tetramethylguanidine (TMG), producing β-substituted phenyl cyanoacrylates with 84% yield. However, fatty substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole and acetone cyanohydrin underwent Michael addition reaction in the presence of MgBu2 or TMG, the product yield was up to 99%. The possible reaction mechanism when using different basic catalysts was discussed.
Cyano compounds are a class of organic compounds with great value. Two different kinds of reactions have been reported using acetone cyanohydrin as reagent and substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole as substrate. The reaction pathway depends on the basic catalysts used when aromatic substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole was used as the substrate. Michael addition reaction occurred in the presence of MgBu2 with the product yield up to 95%, while alcoholysis reaction of amide occurred in the presence of 1, 1, 3, 3-tetramethylguanidine (TMG), producing β-substituted phenyl cyanoacrylates with 84% yield. However, fatty substituted 3, 5-dimethyl-N-α, β-unsaturated acyl pyrazole and acetone cyanohydrin underwent Michael addition reaction in the presence of MgBu2 or TMG, the product yield was up to 99%. The possible reaction mechanism when using different basic catalysts was discussed.
2020, 40(9): 2879-2887
doi: 10.6023/cjoc202005005
Abstract:
Repalcement of C=C bond with an isoeletronic and isosturctural B—N bond is an effective way to tune the photophyscial properties of polycylic aromatic hydrocarbons (PAHs), which have become the hot topic in the filed of optoelectronics. There are relatively smalll number of the non-planar BN-PAHs exsited, compared to the large number of planar BN-PAHs being synthesized. In this paper, the synthesis and properties of two series of non-planar BN[4]helicenes are discribed. The synthesis is quite straightforward by sequence of Suzuki cross coupling reaction, electrophilic borylation and nuleophilic substitution reactions. All of the target BN-[4]helicenes were characterized by 1H NMR, 13C NMR and 11B NMR. One of the BN-[4]helicene was also unmbigiously confired by X-ray crystal analysis, which showed the typical helically twisted geometries. Futhermore, the BC4N ring in the BN[4]helicene exhibited weak aromaticites, wihch were quantitified by experimental and theorectical calculations. Furthermore, both of the two series of BN[4]helicene showed significant redshift of their absorption spectra and slightly blueshift emission spectra comparing to the all-carbon [4]helicene analogue. Also, good fluorescence quantum yields range from 0.42 to 0.70 were obtained for the two series of BN[4]helicenes.
Repalcement of C=C bond with an isoeletronic and isosturctural B—N bond is an effective way to tune the photophyscial properties of polycylic aromatic hydrocarbons (PAHs), which have become the hot topic in the filed of optoelectronics. There are relatively smalll number of the non-planar BN-PAHs exsited, compared to the large number of planar BN-PAHs being synthesized. In this paper, the synthesis and properties of two series of non-planar BN[4]helicenes are discribed. The synthesis is quite straightforward by sequence of Suzuki cross coupling reaction, electrophilic borylation and nuleophilic substitution reactions. All of the target BN-[4]helicenes were characterized by 1H NMR, 13C NMR and 11B NMR. One of the BN-[4]helicene was also unmbigiously confired by X-ray crystal analysis, which showed the typical helically twisted geometries. Futhermore, the BC4N ring in the BN[4]helicene exhibited weak aromaticites, wihch were quantitified by experimental and theorectical calculations. Furthermore, both of the two series of BN[4]helicene showed significant redshift of their absorption spectra and slightly blueshift emission spectra comparing to the all-carbon [4]helicene analogue. Also, good fluorescence quantum yields range from 0.42 to 0.70 were obtained for the two series of BN[4]helicenes.
2020, 40(9): 2888-2894
doi: 10.6023/cjoc202002030
Abstract:
Hydrogen peroxide (H2O2) plays an important role in various physiological and pathological processes in the form of molecular signals. Thus, it is of great significance to detect hydrogen peroxide in living cells or organisms quickly, efficiently and sensitively. In this study, a novel ratiometric fluorescent probe was designed to show the ratiometric fluorescence response to hydrogen peroxide. The probe showed the advantages of good selectivity, high sensitivity, low cytotoxicity and fast reaction rate in hydrogen peroxide detection. The probe also provided excellent performance in detecting both exogenous and endogenous hydrogen peroxide in living cells.
Hydrogen peroxide (H2O2) plays an important role in various physiological and pathological processes in the form of molecular signals. Thus, it is of great significance to detect hydrogen peroxide in living cells or organisms quickly, efficiently and sensitively. In this study, a novel ratiometric fluorescent probe was designed to show the ratiometric fluorescence response to hydrogen peroxide. The probe showed the advantages of good selectivity, high sensitivity, low cytotoxicity and fast reaction rate in hydrogen peroxide detection. The probe also provided excellent performance in detecting both exogenous and endogenous hydrogen peroxide in living cells.
2020, 40(9): 2912-2918
doi: 10.6023/cjoc202005004
Abstract:
A novel visible-light-introduced reaction for the construction of phenols via hydroxylation of aryl halides has been developed. The reaction has been achieved in high yield under mild conditions by using iodine as photocatalyst, which is cheap, easy to handle and environmentally friendly. A variety of phenols were obtained in up to 92% yields. Moreover, aryl chlorides were also successfully employed as substrates, affording the target phenols in good isolated yields. It might provide promising protocol for the synthesis of phenol derivatives. Its application was performed by the synthesis of 5-acetyl-4-hy-droxy-2-methoxybenzyl diisopropylcarbamodithioate, which displayed significant anti-proliferation effect.
A novel visible-light-introduced reaction for the construction of phenols via hydroxylation of aryl halides has been developed. The reaction has been achieved in high yield under mild conditions by using iodine as photocatalyst, which is cheap, easy to handle and environmentally friendly. A variety of phenols were obtained in up to 92% yields. Moreover, aryl chlorides were also successfully employed as substrates, affording the target phenols in good isolated yields. It might provide promising protocol for the synthesis of phenol derivatives. Its application was performed by the synthesis of 5-acetyl-4-hy-droxy-2-methoxybenzyl diisopropylcarbamodithioate, which displayed significant anti-proliferation effect.
2020, 40(9): 2919-2928
doi: 10.6023/cjoc202005035
Abstract:
Two highly electron-deficient, novel isoindigo (IID) derivative acceptor units, including isatin-fused acenaphthenequinone imide (A1) and nitrogen-doped isatin-fused acenaphthenequinone imide (A2), were designed and synthesized via Knoevenagel consendation reaction. In comparison with the well-known IID unit, both A1 and A2 acceptor units exhibit reduced LUMO energy levels (ca. -4.0 eV) and extended π-conjugation backbone owing to the incorporation of strongly electron-withdrawing acenaphthenequinone imide. The properties observed here for both A1 and A2 are thus indicative of promising potential in the development of n-type organic semiconductors. On the basis of both A1 and A2 acceptor units, two A-A type organic π-conjugated molecules (BA1 and BA2) were further designed and synthesized by self-coupling of two identical A1 or A2 acceptor units. The effect of pyridal nitrogen on the backbone structure, optical absorption, energy level, and carrier mobility of the as-prepared π-conjugated molecules is studied systematically. The comparative investigation reveals that self-coupling of dual acceptor units into BA1 and BA2 not only endows them with extended conjugation backbone and enhanced molecular symmetry, but also improves their light-capturing abilities in the whole ultraviolet-visible region as relative to their parent acceptor units (A1 and A2). Moreover, the pyridal N-containing BA1 and BA2 possess enhanced backbone coplanarity and electron affinity as compared to their parent units (A1 and A2), thereby leading to reduced HOMO and LUMO energy levels. Finally, n-type thin-film transistors are further fabricated by adopting both BA1 and BA2 as the active layers, affording the electron motilities of 1.64×10-3 and 2.52×10-3 cm2·V-1·s-1, respectively.
Two highly electron-deficient, novel isoindigo (IID) derivative acceptor units, including isatin-fused acenaphthenequinone imide (A1) and nitrogen-doped isatin-fused acenaphthenequinone imide (A2), were designed and synthesized via Knoevenagel consendation reaction. In comparison with the well-known IID unit, both A1 and A2 acceptor units exhibit reduced LUMO energy levels (ca. -4.0 eV) and extended π-conjugation backbone owing to the incorporation of strongly electron-withdrawing acenaphthenequinone imide. The properties observed here for both A1 and A2 are thus indicative of promising potential in the development of n-type organic semiconductors. On the basis of both A1 and A2 acceptor units, two A-A type organic π-conjugated molecules (BA1 and BA2) were further designed and synthesized by self-coupling of two identical A1 or A2 acceptor units. The effect of pyridal nitrogen on the backbone structure, optical absorption, energy level, and carrier mobility of the as-prepared π-conjugated molecules is studied systematically. The comparative investigation reveals that self-coupling of dual acceptor units into BA1 and BA2 not only endows them with extended conjugation backbone and enhanced molecular symmetry, but also improves their light-capturing abilities in the whole ultraviolet-visible region as relative to their parent acceptor units (A1 and A2). Moreover, the pyridal N-containing BA1 and BA2 possess enhanced backbone coplanarity and electron affinity as compared to their parent units (A1 and A2), thereby leading to reduced HOMO and LUMO energy levels. Finally, n-type thin-film transistors are further fabricated by adopting both BA1 and BA2 as the active layers, affording the electron motilities of 1.64×10-3 and 2.52×10-3 cm2·V-1·s-1, respectively.
2020, 40(9): 2929-2937
doi: 10.6023/cjoc202002027
Abstract:
Four squaraine derivatives SQ, DISQ, MeSQ and DIMeSQ with different substitution indole modifications were synthesized through condensation reaction. Squaraine derivative is one kind of D-A-D configuration dyes, which is formed by connecting squaraine with two electron-rich groups through conjugation. The squaraine derivatives were characterized by 1H NMR, 13C NMR and high resolution mass spectrometry. The photophysical properties of these squaraine derivatives were studied, such as UV-visible absorption, fluorescence emission, fluorescence quantum yield, fluorescence lifetimes, singlet oxygen quantum yields, and so on. The results showed that, SQ, DISQ, MeSQ and DIMeSQ showed stronger absorption band at 600~700 nm and emission band at 620~800 nm in dichloromethane, which were in near-infrared filed. These four squaraine derivatives were used for singlet oxygen generation, and the highest singlet oxygen quantum yield (6%) was observed for DISQ, which is twice as high as that of DIMeSQ (3%). It is proposed that iodine-substituted and N-hydrogen-substituted molecules are more conducive to intersystem crossing than N-methyl substituted molecules. In addition, It is confirmed that the intramolecular N—H…O force is beneficial to the intersystem crossing of molecules by combining single crystal structure and theoretical calculations. It showed that DISQ could be used as a potential drug for photodynamic therapy.
Four squaraine derivatives SQ, DISQ, MeSQ and DIMeSQ with different substitution indole modifications were synthesized through condensation reaction. Squaraine derivative is one kind of D-A-D configuration dyes, which is formed by connecting squaraine with two electron-rich groups through conjugation. The squaraine derivatives were characterized by 1H NMR, 13C NMR and high resolution mass spectrometry. The photophysical properties of these squaraine derivatives were studied, such as UV-visible absorption, fluorescence emission, fluorescence quantum yield, fluorescence lifetimes, singlet oxygen quantum yields, and so on. The results showed that, SQ, DISQ, MeSQ and DIMeSQ showed stronger absorption band at 600~700 nm and emission band at 620~800 nm in dichloromethane, which were in near-infrared filed. These four squaraine derivatives were used for singlet oxygen generation, and the highest singlet oxygen quantum yield (6%) was observed for DISQ, which is twice as high as that of DIMeSQ (3%). It is proposed that iodine-substituted and N-hydrogen-substituted molecules are more conducive to intersystem crossing than N-methyl substituted molecules. In addition, It is confirmed that the intramolecular N—H…O force is beneficial to the intersystem crossing of molecules by combining single crystal structure and theoretical calculations. It showed that DISQ could be used as a potential drug for photodynamic therapy.
2020, 40(9): 2949-2955
doi: 10.6023/cjoc202004007
Abstract:
A near-infrared fluorescent probe (6) was designed and synthesized by using 2-(6-(dimethylamino)naphthalen-2-yl)-7-hydroxy-4H-chromen-4-one as report group and 2-picolinate as recognition group. The probe was identified by 1H NMR, 13C NMR, MS and elemental analysis. The probe could react specifically with Cu2+ and its fluorescence intensity increased obviously at 655 nm, at the meantime, the color change of the solution can be seen by naked eyes. A linear relationship was obtained between the fluorescence intensity and concentration of Cu2+ in the range of 0~2.0×10-5 mol/L, and the detection limit was 3.2×10-8 mol/L. The mechanism study showed that Cu2+ catalyzed the cleavage of the ester bond and strongly fluorescent 2-[6-(N, N-dimethylamino)naphthyl]-7-hydroxy-4H-chromen-4-one (5) was generated. In addition, the probe 6 could be used for fluorescence imaging of Cu2+ in living cells.
A near-infrared fluorescent probe (6) was designed and synthesized by using 2-(6-(dimethylamino)naphthalen-2-yl)-7-hydroxy-4H-chromen-4-one as report group and 2-picolinate as recognition group. The probe was identified by 1H NMR, 13C NMR, MS and elemental analysis. The probe could react specifically with Cu2+ and its fluorescence intensity increased obviously at 655 nm, at the meantime, the color change of the solution can be seen by naked eyes. A linear relationship was obtained between the fluorescence intensity and concentration of Cu2+ in the range of 0~2.0×10-5 mol/L, and the detection limit was 3.2×10-8 mol/L. The mechanism study showed that Cu2+ catalyzed the cleavage of the ester bond and strongly fluorescent 2-[6-(N, N-dimethylamino)naphthyl]-7-hydroxy-4H-chromen-4-one (5) was generated. In addition, the probe 6 could be used for fluorescence imaging of Cu2+ in living cells.
2020, 40(9): 2963-2970
doi: 10.6023/cjoc202003025
Abstract:
To discover novel insecticide with improved activity, a series of meta-diamide compounds containing cyclopropyl moiety were synthesized on the principle of biologically active factor splicing. The structures of synthetic derivatives were characterized by 1H NMR, 13C NMR and HRMS. Preliminary bioassay data showed that some of the title compounds exhibited good insecticidal activities against Plutella xylostella and Chilo suppressalis. Among them, the mortality of N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-3-(N-(cyclopropylmethyl)benzamido)-2-fluorobenzamide (6d) and 3-(N-(cyclopropylmethyl)benzamido)-N-(2, 6-dibromo-4-(perfluoropropan-2-yl)phenyl)-2-fluorobenzamide (6e) was 100% against Plute-lla xylostella at 1 mg/L, and the mortality of compound 6d was 100% against Chilo suppressalis at 5 mg/L.
To discover novel insecticide with improved activity, a series of meta-diamide compounds containing cyclopropyl moiety were synthesized on the principle of biologically active factor splicing. The structures of synthetic derivatives were characterized by 1H NMR, 13C NMR and HRMS. Preliminary bioassay data showed that some of the title compounds exhibited good insecticidal activities against Plutella xylostella and Chilo suppressalis. Among them, the mortality of N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-3-(N-(cyclopropylmethyl)benzamido)-2-fluorobenzamide (6d) and 3-(N-(cyclopropylmethyl)benzamido)-N-(2, 6-dibromo-4-(perfluoropropan-2-yl)phenyl)-2-fluorobenzamide (6e) was 100% against Plute-lla xylostella at 1 mg/L, and the mortality of compound 6d was 100% against Chilo suppressalis at 5 mg/L.
2020, 40(9): 2971-2979
doi: 10.6023/cjoc202005075
Abstract:
In order to discover novel compounds with high-activity to control aphid, aphid alarm pheromone (E)-β-farnesene (EBF) was chosen as lead compound and 15 EBF analogues were designed and synthesized by replacing unstable conjugated double bond of EBF with 1, 2, 3-thiadiazole. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis. Repellent activity results indicated that analogues displayed better repellent activity against Myzus persicae (Sulzer). Among which compounds N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(2-naphthyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8d), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(4-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8l) and N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(5-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8m) exhibited excellent repellent activity of 63.1%, 61.3% and 63.4% respectively. The aphicidal bioassay results showed that most analogues exhibited considerable aphicidal activity against Myzus persicae. Especially, analogues N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(4-CN-phenyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8b), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(6-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8g), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(2-pyridyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8j), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(3-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8k), 8l, 8m and N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(5-methyl-1, 3, 4-thiadiazole-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8o) exhibited high activity with LC50 values of 10.2, 9.0, 25.1, 31.7, 8.4, 12.8 and 9.6 μg/mL, respectively, which were higher than the lead compound (E)-β-farnesene, but lower than commercial insecticide pymetrozine with LC50 of 7.1 μg/mL.
In order to discover novel compounds with high-activity to control aphid, aphid alarm pheromone (E)-β-farnesene (EBF) was chosen as lead compound and 15 EBF analogues were designed and synthesized by replacing unstable conjugated double bond of EBF with 1, 2, 3-thiadiazole. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis. Repellent activity results indicated that analogues displayed better repellent activity against Myzus persicae (Sulzer). Among which compounds N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(2-naphthyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8d), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(4-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8l) and N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(5-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8m) exhibited excellent repellent activity of 63.1%, 61.3% and 63.4% respectively. The aphicidal bioassay results showed that most analogues exhibited considerable aphicidal activity against Myzus persicae. Especially, analogues N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(4-CN-phenyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8b), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(6-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8g), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(2-pyridyl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8j), N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(3-methyl-pyridine-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8k), 8l, 8m and N-((E)-3, 7-dimethyl-2, 6-octadien-1-yl)-N-(5-methyl-1, 3, 4-thiadiazole-2-yl)-4-methyl-1, 2, 3-thiadiazole-5-carboxamide (8o) exhibited high activity with LC50 values of 10.2, 9.0, 25.1, 31.7, 8.4, 12.8 and 9.6 μg/mL, respectively, which were higher than the lead compound (E)-β-farnesene, but lower than commercial insecticide pymetrozine with LC50 of 7.1 μg/mL.
2020, 40(9): 2980-2987
doi: 10.6023/cjoc202005006
Abstract:
In medicinal chemistry, the structural modification of natural product and skeleton hybridization strategies is important way to improve the biological activity of template compound and find highly active lead compounds. In this work, two series of cinnamic acid-coumarin ester analogs were synthesized by using cinnamic acid and hydroxycoumarin as raw materials. And the tyrosinase inhibitory activity of the synthesized compounds was evaluated. The results indicated that the cinnamic acid-coumarin analogs had favourable tyrosinase inhibitory activity, especially 2-oxo-2H-benzopyran-4-yl(E)-3-(4-hydroxyphenyl)propenyl ester (C8), 2-oxo-2H-benzopyran-7-yl(E)-3-(4-hydroxyphenyl)propenyl ester and (D8) with IC50 of (10.7±0.7) and (2.2±0.2) μmol·L-1, respectively, which are 3 and 13 times that of kojic acid (IC50 (28.5±1.1) μmol·L-1). The structure-activity relationship analysis results showed that the introduction of substituents like F, Cl, and OH could efficiently enhance the tyrosinase inhibitory activity, and the inhibitory activity of condensation product of substituted cinnamic acid with 7-hydroxycoumarin was higher than that of substituted cinnamic acid with 4-hydroxycoumarin. Kinetic studies showed that the inhibitions of tyrosinase by compounds C8 and D8 are reversible mixed-type inhibitory effects. KI values of C8 and D8 were 1.07 and 20.61 μmol·L-1, respectively, and KIS values were 3.72 and 27.09 μmol·L-1, respectively. Finally, molecular docking was carried out to simulate the docking between compounds C8 and D8 with tyrosinase.
In medicinal chemistry, the structural modification of natural product and skeleton hybridization strategies is important way to improve the biological activity of template compound and find highly active lead compounds. In this work, two series of cinnamic acid-coumarin ester analogs were synthesized by using cinnamic acid and hydroxycoumarin as raw materials. And the tyrosinase inhibitory activity of the synthesized compounds was evaluated. The results indicated that the cinnamic acid-coumarin analogs had favourable tyrosinase inhibitory activity, especially 2-oxo-2H-benzopyran-4-yl(E)-3-(4-hydroxyphenyl)propenyl ester (C8), 2-oxo-2H-benzopyran-7-yl(E)-3-(4-hydroxyphenyl)propenyl ester and (D8) with IC50 of (10.7±0.7) and (2.2±0.2) μmol·L-1, respectively, which are 3 and 13 times that of kojic acid (IC50 (28.5±1.1) μmol·L-1). The structure-activity relationship analysis results showed that the introduction of substituents like F, Cl, and OH could efficiently enhance the tyrosinase inhibitory activity, and the inhibitory activity of condensation product of substituted cinnamic acid with 7-hydroxycoumarin was higher than that of substituted cinnamic acid with 4-hydroxycoumarin. Kinetic studies showed that the inhibitions of tyrosinase by compounds C8 and D8 are reversible mixed-type inhibitory effects. KI values of C8 and D8 were 1.07 and 20.61 μmol·L-1, respectively, and KIS values were 3.72 and 27.09 μmol·L-1, respectively. Finally, molecular docking was carried out to simulate the docking between compounds C8 and D8 with tyrosinase.
2020, 40(9): 2988-2993
doi: 10.6023/cjoc202003043
Abstract:
In the deep eutectic solvents (DES) consisted of choline chloride/zinc chloride(ChCl/ZnCl2), a series of N-substi-tuted decahydroacridine-1, 8-diones and decahydroacridine-1, 8-diones were synthesized from diketones, aromatic aldehydes, ammonium acetates or aromatic amines with 75%~92% yields at 80~90 ℃ in 1~2 h. The advantages of the method are wild reaction condition, simple operation, short reaction time, high yield and friendly to environment.
In the deep eutectic solvents (DES) consisted of choline chloride/zinc chloride(ChCl/ZnCl2), a series of N-substi-tuted decahydroacridine-1, 8-diones and decahydroacridine-1, 8-diones were synthesized from diketones, aromatic aldehydes, ammonium acetates or aromatic amines with 75%~92% yields at 80~90 ℃ in 1~2 h. The advantages of the method are wild reaction condition, simple operation, short reaction time, high yield and friendly to environment.
2020, 40(9): 2956-2962
doi: 10.6023/cjoc202006001
Abstract:
A novel colorimetric and long-wavelength fluorescent probe (SR) based on seminaphthorhodafluor dye was designed and synthesized, which was used to detect H2S through the thiolysis reaction of dinitrophenyl ether and unique OFF-ON mechanism based on the spiro-ring of probe SR. The fluorescent intensity (635 nm) and absorbance (590 nm) changes exhibited an excellent linear relationship with the H2S concentration ranging from 2.00 to 10.00 μmol/L and the detection limits were 0.50 and 1.00 μmol/L, respectively. Ions interference experiments showed that probe SR had an excellent anti-interference ability and could be used to detect H2S in complex systems. The probe SR was further exploited for filter paper, hydrogel and Hela cells for the rapid and convenient detection of H2S, which extended the applications of fluorescent probes for the detection of H2S in chemistry and the environment.
A novel colorimetric and long-wavelength fluorescent probe (SR) based on seminaphthorhodafluor dye was designed and synthesized, which was used to detect H2S through the thiolysis reaction of dinitrophenyl ether and unique OFF-ON mechanism based on the spiro-ring of probe SR. The fluorescent intensity (635 nm) and absorbance (590 nm) changes exhibited an excellent linear relationship with the H2S concentration ranging from 2.00 to 10.00 μmol/L and the detection limits were 0.50 and 1.00 μmol/L, respectively. Ions interference experiments showed that probe SR had an excellent anti-interference ability and could be used to detect H2S in complex systems. The probe SR was further exploited for filter paper, hydrogel and Hela cells for the rapid and convenient detection of H2S, which extended the applications of fluorescent probes for the detection of H2S in chemistry and the environment.
2020, 40(9): 2994-2996
doi: 10.6023/cjoc202000055
Abstract:
2020, 40(9): 2999-3000
doi: 10.6023/cjoc202000057
Abstract:
2020, 40(9): 3001-3003
doi: 10.6023/cjoc202000058
Abstract:
2020, 40(9): 3004-3006
doi: 10.6023/cjoc202000059
Abstract:
2020, 40(9): 3007-3008
doi: 10.6023/cjoc202000060
Abstract:
2020, 40(9): 3009-3011
doi: 10.6023/cjoc202000061
Abstract:
2020, 40(9): 3012-3013
doi: 10.6023/cjoc202000062
Abstract:
2020, 40(9): 3014-3016
doi: 10.6023/cjoc202000063
Abstract:
