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2020 Volume 40 Issue 2
2020, 40(2): 255-275
doi: 10.6023/cjoc201910009
Abstract:
Chiral aryl alcohols are prevalent in a broad range of biologically active compounds, pharmaceutical agents and natural products. They also constitute a broad class of optically active building blocks for the synthesis of important chiral compounds. In recent years, organoboron reagents are widely used in organic synthesis as they possess advantages of ready availability, low toxicity, good air and moisture stability as well as high functional group compatibility. Since the first report of rhodium-catalyzed asymmetric addition of aryl boronic acids to aryl aldehydes in 1998 by Miyaura, the use of organoboron reagents in asymmetric addition to various carbonyl compounds under various transition-metal catalyses has been intensively investigated. Over the past two decades, transition metal-catalyzed asymmetric addition of organoboron reagents to aldehydes and ketones has proved as one of the most direct and powerful methods for accessing versatile optically active alcohols. The development and progress of a wide range of chiral ligands for Rh, Ru, Pd, Ir, Cu, Ni and Co catalysis for asymmetric addition of organoboron reagents to aldehydes and ketones are summarized, and the achievements in enantioselective synthesis of chiral aryl alcohols and their applications in the synthesis of related biocative products are described. Among them, rhodium and ruthenium-catalyzed enantioselective additions have received considerable attention. In the cases of activated carbonyl compounds such as α-aryl ketoesters and α-diaryl diketones, excellent results can be attained in terms of both yield and enantioselectivity. However, it remains a daunting challenge for highly enantioselective addition to simple unactivated aldehydes and ketones owing to the difficulty in overcoming stereo differentiation. Future efforts in the community would focus on developing new effective transition-metal catalysts in addressing these issues by promoting efficient transformation and controlling excellent enantioselectivity.
Chiral aryl alcohols are prevalent in a broad range of biologically active compounds, pharmaceutical agents and natural products. They also constitute a broad class of optically active building blocks for the synthesis of important chiral compounds. In recent years, organoboron reagents are widely used in organic synthesis as they possess advantages of ready availability, low toxicity, good air and moisture stability as well as high functional group compatibility. Since the first report of rhodium-catalyzed asymmetric addition of aryl boronic acids to aryl aldehydes in 1998 by Miyaura, the use of organoboron reagents in asymmetric addition to various carbonyl compounds under various transition-metal catalyses has been intensively investigated. Over the past two decades, transition metal-catalyzed asymmetric addition of organoboron reagents to aldehydes and ketones has proved as one of the most direct and powerful methods for accessing versatile optically active alcohols. The development and progress of a wide range of chiral ligands for Rh, Ru, Pd, Ir, Cu, Ni and Co catalysis for asymmetric addition of organoboron reagents to aldehydes and ketones are summarized, and the achievements in enantioselective synthesis of chiral aryl alcohols and their applications in the synthesis of related biocative products are described. Among them, rhodium and ruthenium-catalyzed enantioselective additions have received considerable attention. In the cases of activated carbonyl compounds such as α-aryl ketoesters and α-diaryl diketones, excellent results can be attained in terms of both yield and enantioselectivity. However, it remains a daunting challenge for highly enantioselective addition to simple unactivated aldehydes and ketones owing to the difficulty in overcoming stereo differentiation. Future efforts in the community would focus on developing new effective transition-metal catalysts in addressing these issues by promoting efficient transformation and controlling excellent enantioselectivity.
2020, 40(2): 276-283
doi: 10.6023/cjoc201908039
Abstract:
The level of copper (Cu) directly affects the normal operation of the living body and the balance of the natural system. Fluorescence chemosensors with high sensitivity and selectivity are more widely used, although there are various methods for detecting copper ions. The research progress of fluorescence chemosensors for sequential recognition of anions S2-, CN-, H2PO4-, PPi and I-, neutral molecules ATP, ADP and biological thiols by "substitution" method based on Cu2+ is reviewed.
The level of copper (Cu) directly affects the normal operation of the living body and the balance of the natural system. Fluorescence chemosensors with high sensitivity and selectivity are more widely used, although there are various methods for detecting copper ions. The research progress of fluorescence chemosensors for sequential recognition of anions S2-, CN-, H2PO4-, PPi and I-, neutral molecules ATP, ADP and biological thiols by "substitution" method based on Cu2+ is reviewed.
2020, 40(2): 284-299
doi: 10.6023/cjoc201909028
Abstract:
Nitroolefin is an important class of organic synthons. The synthetic method of multicomponent asymmetric cascade reactions involving nitroolefin catalyzed by diarlyprolinol derivatives is quite important for the construction of complex chiral compounds. It is widely used in organic synthesis and new drugs development. In this paper, the multi-component asymmetric cascade synthesis involving nitroalkenes catalyzed by diarlyprolinol derivatives is comprehensively summarized based on the type of target compounds. In detail, the catalyst systems, reaction mechanisms, experimental results, reaction advantages, existing problems and limitations for this synthetic method are introduced respectively. The future development for this synthetic period is further evaluated as well.
Nitroolefin is an important class of organic synthons. The synthetic method of multicomponent asymmetric cascade reactions involving nitroolefin catalyzed by diarlyprolinol derivatives is quite important for the construction of complex chiral compounds. It is widely used in organic synthesis and new drugs development. In this paper, the multi-component asymmetric cascade synthesis involving nitroalkenes catalyzed by diarlyprolinol derivatives is comprehensively summarized based on the type of target compounds. In detail, the catalyst systems, reaction mechanisms, experimental results, reaction advantages, existing problems and limitations for this synthetic method are introduced respectively. The future development for this synthetic period is further evaluated as well.
2020, 40(2): 300-326
doi: 10.6023/cjoc201907055
Abstract:
Aspirin (ASP), the first synthetic drug, is widely used as a non steroidal anti-inflammatory drug. It displays a variety of biological activities, such as anti-thrombosis, anti-inflammatory, anti-tumor, etc. A lot of works about the synthesis and related activity evaluation of its derivatives were reported. There are four kinds of derivatization methods:skeleton derivatization, prodrug derivatization, twin derivatization and metal coordination derivatization. According to the different modification sites, skeleton derivatization could be further divided into C(1)-COOH site modification, C(1)-COOH site and C(2)-OAc site simultaneous modification, C(2)-OAc site modification and benzene ring modification. NO-ASP is the main method to prepare antithrombotic derivatives, and metal coordination modification is the main synthesis scheme of anticancer derivatives. The structure modification and bioactivity research of aspirin in recent twenty years and the synthetic routes of 353 aspirin derivatives and the pharmacological activities of some derivatives are described, which provides a reference for the further development of aspirin derivatives.
Aspirin (ASP), the first synthetic drug, is widely used as a non steroidal anti-inflammatory drug. It displays a variety of biological activities, such as anti-thrombosis, anti-inflammatory, anti-tumor, etc. A lot of works about the synthesis and related activity evaluation of its derivatives were reported. There are four kinds of derivatization methods:skeleton derivatization, prodrug derivatization, twin derivatization and metal coordination derivatization. According to the different modification sites, skeleton derivatization could be further divided into C(1)-COOH site modification, C(1)-COOH site and C(2)-OAc site simultaneous modification, C(2)-OAc site modification and benzene ring modification. NO-ASP is the main method to prepare antithrombotic derivatives, and metal coordination modification is the main synthesis scheme of anticancer derivatives. The structure modification and bioactivity research of aspirin in recent twenty years and the synthetic routes of 353 aspirin derivatives and the pharmacological activities of some derivatives are described, which provides a reference for the further development of aspirin derivatives.
2020, 40(2): 327-338
doi: 10.6023/cjoc201907047
Abstract:
3-(5-Oxazolyl)indole-type natural products such as pimprinine and streptochlorin, widely exist in marine microorganism, because of their diverse biological activity, 3-(5-oxazolyl)indoles show good research and development potential in the field of medicine and pesticide. Numerous studies have been performed to synthesize 3-(5-oxazolyl)indole-type natural products, in which the construction of indole ring and oxazole ring is the most important part. In this paper, the reported natural products with 3-(5-oxazolyl)indole skeleton structure and their biological activities are summarized, and the synthetic methods for 3-(5-oxazolyl)indole skeleton and some of their mechanism are also reviewed. The application prospect of 3-(5-oxazol-yl)indole as a dominant active structure in the future was discussed.
3-(5-Oxazolyl)indole-type natural products such as pimprinine and streptochlorin, widely exist in marine microorganism, because of their diverse biological activity, 3-(5-oxazolyl)indoles show good research and development potential in the field of medicine and pesticide. Numerous studies have been performed to synthesize 3-(5-oxazolyl)indole-type natural products, in which the construction of indole ring and oxazole ring is the most important part. In this paper, the reported natural products with 3-(5-oxazolyl)indole skeleton structure and their biological activities are summarized, and the synthetic methods for 3-(5-oxazolyl)indole skeleton and some of their mechanism are also reviewed. The application prospect of 3-(5-oxazol-yl)indole as a dominant active structure in the future was discussed.
2020, 40(2): 339-350
doi: 10.6023/cjoc201909024
Abstract:
The photocatalytic redox reactions have been widely concerned in organic chemistry due to their green, efficiency and safety. In this review, the cross-coupling/aromatization reactions are described based on photocatalytic organic hydrogen-evolution, which can be used to build organic carbon-carbon and carbon-heteroatom bonds by using a photocatalyst/catalyst dual catalytic system. Hydrogen is the only by-product in these reactions. The system and catalytic mechanisms of organic photocatalytic redox reaction are highlighted.
The photocatalytic redox reactions have been widely concerned in organic chemistry due to their green, efficiency and safety. In this review, the cross-coupling/aromatization reactions are described based on photocatalytic organic hydrogen-evolution, which can be used to build organic carbon-carbon and carbon-heteroatom bonds by using a photocatalyst/catalyst dual catalytic system. Hydrogen is the only by-product in these reactions. The system and catalytic mechanisms of organic photocatalytic redox reaction are highlighted.
2020, 40(2): 351-363
doi: 10.6023/cjoc201909022
Abstract:
Quinoidal heterocyclic (thiophene, pyrrole, furan, etc.) molecules have the characteristics of rigid backbone, low highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) level, narrow band gap and high molar extinction coefficient, and so on. Because of their planar structures, quinoidal molecules usually have strong intermolecular charge transfer ability due to the strong intermolecular interaction. Up to now, quinoidal heterocyclic molecules have become a research hotspot in the field of organic semiconductor materials, especially in the field of organic field effect transistors. According to the structural features of quinoidal heterocyclic molecules and the classification basis of terminal groups, the research progress of quinoidal heterocyclic compounds in molecular design, synthesis and application in recent years is reviewed, and the development of quinoidal heterocyclic molecules is prospected.
Quinoidal heterocyclic (thiophene, pyrrole, furan, etc.) molecules have the characteristics of rigid backbone, low highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) level, narrow band gap and high molar extinction coefficient, and so on. Because of their planar structures, quinoidal molecules usually have strong intermolecular charge transfer ability due to the strong intermolecular interaction. Up to now, quinoidal heterocyclic molecules have become a research hotspot in the field of organic semiconductor materials, especially in the field of organic field effect transistors. According to the structural features of quinoidal heterocyclic molecules and the classification basis of terminal groups, the research progress of quinoidal heterocyclic compounds in molecular design, synthesis and application in recent years is reviewed, and the development of quinoidal heterocyclic molecules is prospected.
2020, 40(2): 364-375
doi: 10.6023/cjoc201908009
Abstract:
Discrete metallacycle complexes have attracted considerable attention because of their widely used in host-guest chemistry, gas adsorption, molecular recognition and catalysis. Thus exploring new framework complexes, studying their physical and chemical properties and applications have become one of the most active and exciting areas of inorganic chemistry, organic chemistry and supramolecular chemistry. Half-sandwich organometallic units based on ruthenium, iridium and rhodium are often utilized to prepare diverse metallacylce complexes due to the following advantages:the solubility of these metal complexes can be enhanced, the hemisphere of the metal center is perfectly shielded, minimizing the complexity of reactions, and the products with different structures are easily synthesized. In this paper, the synthesis and application of discrete type metal framework complexes with half-sandwich structures of ruthenium, iridium and rhodium are reviewed.
Discrete metallacycle complexes have attracted considerable attention because of their widely used in host-guest chemistry, gas adsorption, molecular recognition and catalysis. Thus exploring new framework complexes, studying their physical and chemical properties and applications have become one of the most active and exciting areas of inorganic chemistry, organic chemistry and supramolecular chemistry. Half-sandwich organometallic units based on ruthenium, iridium and rhodium are often utilized to prepare diverse metallacylce complexes due to the following advantages:the solubility of these metal complexes can be enhanced, the hemisphere of the metal center is perfectly shielded, minimizing the complexity of reactions, and the products with different structures are easily synthesized. In this paper, the synthesis and application of discrete type metal framework complexes with half-sandwich structures of ruthenium, iridium and rhodium are reviewed.
2020, 40(2): 376-383
doi: 10.6023/cjoc201907053
Abstract:
N3-Purine nucleoside can be employed as a potent dual inhibitor to inhibit viruses more effectively because it could be possibly recognized by both purine-and pyrimidine-metabolizing enzymes. Herein, an asymmetric transfer hydrogenation via dynamic kinetic resolution of rac-α-(purin-3-yl)cyclopentones has been developed to produce a wide range of carbocyclic N3-purine nucleosides in high yields and excellent stereoselectivities. Moreover, the catalytic system was suitable for rac-α-pyrimidinyl cyclopentones. With additional transformations, several 2'-F-, AcS-, N3-modified carbocyclic nucleosides could be obtained with good to excellent yields and excellent enantioselectivities.
N3-Purine nucleoside can be employed as a potent dual inhibitor to inhibit viruses more effectively because it could be possibly recognized by both purine-and pyrimidine-metabolizing enzymes. Herein, an asymmetric transfer hydrogenation via dynamic kinetic resolution of rac-α-(purin-3-yl)cyclopentones has been developed to produce a wide range of carbocyclic N3-purine nucleosides in high yields and excellent stereoselectivities. Moreover, the catalytic system was suitable for rac-α-pyrimidinyl cyclopentones. With additional transformations, several 2'-F-, AcS-, N3-modified carbocyclic nucleosides could be obtained with good to excellent yields and excellent enantioselectivities.
2020, 40(2): 417-422
doi: 10.6023/cjoc201907016
Abstract:
In order to find high-efficiency antitumor drugs, a series of 2, 4, 6-trisubstituted pyrimidine derivatives containing benzothiazole moiety were designed, synthesized and evaluated for antitumor activities against four cancer cells (EC-109, human esophageal cancer cells; MGC-803, human gastric cancer cells; PC-3, human prostate cancer cells; HepG-2, human liver cancer cells), GES-1 (human normal gastric mucosal epithelial cells), and HEEC (human normal esophagus) using thiazolyl blue (MTT) method. The results showed that some compounds exhibited moderate to strong antitumor activities against MGC-803 and PC-3 cells. Among them, 2-(((4-(4-(pyridin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)-thio)methyl)benzo[d]thiazole (13h) and 2-(((4-(4-(pyrimidin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-methyl)benzo[d]thiazole (13i) showed the most potent antitumor activities against PC-3 cells with IC50 values of 3.82 and 2.29 μmol/L, respectively. The toxicities of compounds 13h and 13i to GES-1 cells were significantly lower than the positive control 5-fluorouracil.
In order to find high-efficiency antitumor drugs, a series of 2, 4, 6-trisubstituted pyrimidine derivatives containing benzothiazole moiety were designed, synthesized and evaluated for antitumor activities against four cancer cells (EC-109, human esophageal cancer cells; MGC-803, human gastric cancer cells; PC-3, human prostate cancer cells; HepG-2, human liver cancer cells), GES-1 (human normal gastric mucosal epithelial cells), and HEEC (human normal esophagus) using thiazolyl blue (MTT) method. The results showed that some compounds exhibited moderate to strong antitumor activities against MGC-803 and PC-3 cells. Among them, 2-(((4-(4-(pyridin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)-thio)methyl)benzo[d]thiazole (13h) and 2-(((4-(4-(pyrimidin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-methyl)benzo[d]thiazole (13i) showed the most potent antitumor activities against PC-3 cells with IC50 values of 3.82 and 2.29 μmol/L, respectively. The toxicities of compounds 13h and 13i to GES-1 cells were significantly lower than the positive control 5-fluorouracil.
2020, 40(2): 423-431
doi: 10.6023/cjoc201909007
Abstract:
A silver-mediated alkynylphosphonation of 1, 4-enynes with diarylphosphine oxides has been developed, by which a wide range of γ-ketophosphine oxides with moderate to good yields were synthesized through radical 1, 2-alkynyl migration. The transformation proceeded with sequential P-centered radical addition to vinyl unit, 3-exo-dig cyclization and 1, 2-alkynyl migration, resulting in the bond-forming events including C-P and C-C bonds to realize difunctionalization of unactivated olefins.
A silver-mediated alkynylphosphonation of 1, 4-enynes with diarylphosphine oxides has been developed, by which a wide range of γ-ketophosphine oxides with moderate to good yields were synthesized through radical 1, 2-alkynyl migration. The transformation proceeded with sequential P-centered radical addition to vinyl unit, 3-exo-dig cyclization and 1, 2-alkynyl migration, resulting in the bond-forming events including C-P and C-C bonds to realize difunctionalization of unactivated olefins.
2020, 40(2): 440-446
doi: 10.6023/cjoc201907012
Abstract:
Two series of novel chrysin derivatives were synthesized, and their antiproliferative activity was evaluated against six human cancer cell lines (MGC-803, BEL-7402, HepG2, HeLa, A549, and SGC-7901) using methyl thiazolyl tetrazolium (MTT) assay. Preliminary bioassay results indicated that 7-((1-(3-fluorophenyl)-1H-1, 2, 3-triazol-4-yl)methoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one (1c) and 7-((1-(2-chlorophenyl)-1H-1, 2, 3-triazol-4-yl)methoxy)-5-hydroxy-2-phenyl-4H-chro-men-4-one (1g) exhibited significantly improved antiproliferative activities against the MGC-803 cell line when compared with the parent compound chrysin and the positive control drug 5-fluorouracil. It demonstrates that compounds 1c and 1g are potential agents for cancer therapy.
Two series of novel chrysin derivatives were synthesized, and their antiproliferative activity was evaluated against six human cancer cell lines (MGC-803, BEL-7402, HepG2, HeLa, A549, and SGC-7901) using methyl thiazolyl tetrazolium (MTT) assay. Preliminary bioassay results indicated that 7-((1-(3-fluorophenyl)-1H-1, 2, 3-triazol-4-yl)methoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one (1c) and 7-((1-(2-chlorophenyl)-1H-1, 2, 3-triazol-4-yl)methoxy)-5-hydroxy-2-phenyl-4H-chro-men-4-one (1g) exhibited significantly improved antiproliferative activities against the MGC-803 cell line when compared with the parent compound chrysin and the positive control drug 5-fluorouracil. It demonstrates that compounds 1c and 1g are potential agents for cancer therapy.
2020, 40(2): 384-390
doi: 10.6023/cjoc201909041
Abstract:
A new PhI(OAc)2-mediated dediazodioxygenation of α-diazo carbonyls was reported. By using the characteristics of the in-situ-generated O-centered radicals from the interaction of PhI(OAc)2 and N-hydroxy phthalimide (or N-hydroxy succinimide), O-centered radical-triggered dioxygenation of α-diazo carbonyls was achieved in this transformation, which led to the synthesis of a series of α, α-dioxoarylketones and α, α-dioxoesters with moderate to good yields. Based on the experimental results and literature reports, the possible reaction mechanism was proposed, which involved O-centered radical addition, C-N bond homolysis and radical cross coupling. In addition, the reaction featured mild conditions and simple operation without any catalyst.
A new PhI(OAc)2-mediated dediazodioxygenation of α-diazo carbonyls was reported. By using the characteristics of the in-situ-generated O-centered radicals from the interaction of PhI(OAc)2 and N-hydroxy phthalimide (or N-hydroxy succinimide), O-centered radical-triggered dioxygenation of α-diazo carbonyls was achieved in this transformation, which led to the synthesis of a series of α, α-dioxoarylketones and α, α-dioxoesters with moderate to good yields. Based on the experimental results and literature reports, the possible reaction mechanism was proposed, which involved O-centered radical addition, C-N bond homolysis and radical cross coupling. In addition, the reaction featured mild conditions and simple operation without any catalyst.
2020, 40(2): 391-397
doi: 10.6023/cjoc201907006
Abstract:
Based on the combination principle in drug design, thirteen pyrazolo[3, 4-d]pyrimidine derivatives containing indole moiety were designed and synthesized. The target compounds were confirmed by 1H NMR, 13C NMR and HRMS. Their in vitro cytotoxicity against four human cancer cell lines (HeLa、MGC-803、MCF-7、BEL-7404) has been investigated and most of the tested compounds displayed moderate antiproliferative activity. Especially, compound 5m exhibited the highest level of antiproliferative activity with an IC50 value < 30 μmol·L-1 for HeLa, MGC-803 and MCF-7. IC50 value of methyl 3-((4-oxo-1-phenyl-4, 5-dihydro-1H-pyrazolo[3, 4-d]pyrimidin-6-yl)thio)-1H-indole-6-carboxylate (5m) to MCF-7 was (4.02±0.92) μmol·L-1, which was better than etoposide (10.1±0.62 μmol·L-1) and camptothecin (5.93±0.56 μmol·L-1). Further biological evaluation of these compounds suggested that these compounds showed selective inhibitory activity against Topo Ⅱ as a possible intracellular target, and all compounds didn't show inhibitory activity against Topo Ⅰ.
Based on the combination principle in drug design, thirteen pyrazolo[3, 4-d]pyrimidine derivatives containing indole moiety were designed and synthesized. The target compounds were confirmed by 1H NMR, 13C NMR and HRMS. Their in vitro cytotoxicity against four human cancer cell lines (HeLa、MGC-803、MCF-7、BEL-7404) has been investigated and most of the tested compounds displayed moderate antiproliferative activity. Especially, compound 5m exhibited the highest level of antiproliferative activity with an IC50 value < 30 μmol·L-1 for HeLa, MGC-803 and MCF-7. IC50 value of methyl 3-((4-oxo-1-phenyl-4, 5-dihydro-1H-pyrazolo[3, 4-d]pyrimidin-6-yl)thio)-1H-indole-6-carboxylate (5m) to MCF-7 was (4.02±0.92) μmol·L-1, which was better than etoposide (10.1±0.62 μmol·L-1) and camptothecin (5.93±0.56 μmol·L-1). Further biological evaluation of these compounds suggested that these compounds showed selective inhibitory activity against Topo Ⅱ as a possible intracellular target, and all compounds didn't show inhibitory activity against Topo Ⅰ.
2020, 40(2): 398-407
doi: 10.6023/cjoc201907056
Abstract:
Three kinds of 1, 5-benzothiazepines containing 1, 2, 3-triazole, 3-(1H-1, 2, 3-triazolyl)-4-aryl-2, 5-dihydro-1, 5-benzo-thiazepines (5a~5f), 3-(2H-1, 2, 3-triazolyl)-4-aryl-2, 3-dihydro-1, 5-benzothiazepines (6a~6f) and 3-(1H-1, 2, 3-triazolyl)-4-aryl-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepines (7a~7f), were designed and synthesized. The synthesis conditions of intermediates and target products were studied. Two by-products were separated and their structures were determined. The antifungal activity test of the target products showed that compounds 5a~5f exhibited high inhibitory effects against fungi especially for Cryptococcus neoformans. The preliminary study on the structure-activity relationship of antifungal activity reveled that 1H-1, 2, 3-triazolyl and C=C double bond were the key function groups in the antifungal activity of 5a~5f.
Three kinds of 1, 5-benzothiazepines containing 1, 2, 3-triazole, 3-(1H-1, 2, 3-triazolyl)-4-aryl-2, 5-dihydro-1, 5-benzo-thiazepines (5a~5f), 3-(2H-1, 2, 3-triazolyl)-4-aryl-2, 3-dihydro-1, 5-benzothiazepines (6a~6f) and 3-(1H-1, 2, 3-triazolyl)-4-aryl-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepines (7a~7f), were designed and synthesized. The synthesis conditions of intermediates and target products were studied. Two by-products were separated and their structures were determined. The antifungal activity test of the target products showed that compounds 5a~5f exhibited high inhibitory effects against fungi especially for Cryptococcus neoformans. The preliminary study on the structure-activity relationship of antifungal activity reveled that 1H-1, 2, 3-triazolyl and C=C double bond were the key function groups in the antifungal activity of 5a~5f.
2020, 40(2): 408-416
doi: 10.6023/cjoc201907026
Abstract:
Coumarin and pyrazolo[3, 4-b]pyridine are structurally essential elements in biologically active natural compounds and are extremely important in medicinal chemistry by serving as key pharmacophores in drug discovery. In this article, the efficient synthesis of coumarin-fused pyrazolo[3, 4-b]pyridine via three-component domino reaction of aldehydes, coumarin derivative and 5-aminopyrazole in one step catalyzed by niobic acid modified with phosphoric acid under microwave irradiation has been achieved. The one-pot procedure, eco-friendly catalyst and solvent as well as simple operation are the key features of this method. The structures of the products were identified by IR, NMR, and HRMS spectra.
Coumarin and pyrazolo[3, 4-b]pyridine are structurally essential elements in biologically active natural compounds and are extremely important in medicinal chemistry by serving as key pharmacophores in drug discovery. In this article, the efficient synthesis of coumarin-fused pyrazolo[3, 4-b]pyridine via three-component domino reaction of aldehydes, coumarin derivative and 5-aminopyrazole in one step catalyzed by niobic acid modified with phosphoric acid under microwave irradiation has been achieved. The one-pot procedure, eco-friendly catalyst and solvent as well as simple operation are the key features of this method. The structures of the products were identified by IR, NMR, and HRMS spectra.
2020, 40(2): 432-439
doi: 10.6023/cjoc201907020
Abstract:
The cell division cycle 25 phosphatase B (Cdc25B) is involved in carcinogenic transformation and is a potential drug target for anticancer therapy. In order to screen Cdc25B inhibitors, 1, 3-selenazole was selected as the core block, and 1, 2, 4-triazole Schiff base was bridged into 2-(1, 2, 4-triazol-3-yl)thio-N-(4-phenyl-1, 3-selenazolyl-2-yl)acetamide (TATS) by the amide thioether bond. The molecular docking simulation of TATS1 with Cdc25B was first performed to identify the rationality of the core function of 1, 3-selenazole. The results show that 1, 3-selenazole can be tightly embedded in the Cdc25B structure and perform N-H…PI non-bond weak interaction with the important catalytic site Arg492, which indicates that 1, 3-selenazole plays a central role. The amide carbonyl oxygen atom forms a hydrogen bond with Arg492 and Arg488, indicating that the introduction of the amide thioether bond is reasonable. Based on the theoretical docking study, thirteen new target compounds TATS1~TATS13 were designed and synthesized through modification in two regions of 1, 2, 4-triazole Schiff base. The inhibition against Cdc25B of target molecules and important intermediates was tested respectively. As a result, the inhibitory activities of the intermediates are not good, 12 target compounds have better biological activity than the positive reference substance Na3VO4, the modifications of two regions of 1, 2, 4-triazole also have a significant effect, which suggests that these compounds are expected to be a potential inhibitor of Cdc25B.
The cell division cycle 25 phosphatase B (Cdc25B) is involved in carcinogenic transformation and is a potential drug target for anticancer therapy. In order to screen Cdc25B inhibitors, 1, 3-selenazole was selected as the core block, and 1, 2, 4-triazole Schiff base was bridged into 2-(1, 2, 4-triazol-3-yl)thio-N-(4-phenyl-1, 3-selenazolyl-2-yl)acetamide (TATS) by the amide thioether bond. The molecular docking simulation of TATS1 with Cdc25B was first performed to identify the rationality of the core function of 1, 3-selenazole. The results show that 1, 3-selenazole can be tightly embedded in the Cdc25B structure and perform N-H…PI non-bond weak interaction with the important catalytic site Arg492, which indicates that 1, 3-selenazole plays a central role. The amide carbonyl oxygen atom forms a hydrogen bond with Arg492 and Arg488, indicating that the introduction of the amide thioether bond is reasonable. Based on the theoretical docking study, thirteen new target compounds TATS1~TATS13 were designed and synthesized through modification in two regions of 1, 2, 4-triazole Schiff base. The inhibition against Cdc25B of target molecules and important intermediates was tested respectively. As a result, the inhibitory activities of the intermediates are not good, 12 target compounds have better biological activity than the positive reference substance Na3VO4, the modifications of two regions of 1, 2, 4-triazole also have a significant effect, which suggests that these compounds are expected to be a potential inhibitor of Cdc25B.
2020, 40(2): 447-453
doi: 10.6023/cjoc201907037
Abstract:
A highly method for intramolecular oxidative coupling reaction of thiosemicarbazone promoted by hypervalent iodine reagent was reported. 2-Amino-1, 3, 4-thiadiazole derivatives could be synthesized effectively. Hypervalent iodine could be used as a mild reagent with low toxicity, low cost, easy circulation and operation. The reaction had the advantages of easy preparation of raw materials, simple operation and better performance. The applicability of substrates and the reaction mechanism were also preliminarily studied.
A highly method for intramolecular oxidative coupling reaction of thiosemicarbazone promoted by hypervalent iodine reagent was reported. 2-Amino-1, 3, 4-thiadiazole derivatives could be synthesized effectively. Hypervalent iodine could be used as a mild reagent with low toxicity, low cost, easy circulation and operation. The reaction had the advantages of easy preparation of raw materials, simple operation and better performance. The applicability of substrates and the reaction mechanism were also preliminarily studied.
2020, 40(2): 454-461
doi: 10.6023/cjoc201907046
Abstract:
The C(5) C-H fluorination of 8-aminoqunolines has attracted much attention recently. However, transition-metal catalyst and electrophilic fluorination reagents were required in most of these reactions. Transition-metal catalyst free C(5) C-H nucleophilic fluorination of 8-aminoqunolines was reviewed. This reaction was mediated by a hypervalent iodine reagent and employed cheap, safe and stable silver fluoride as the nucleophilic fluorination reagent. The reaction proceeded without inert gas protection. It possess the merits of simple and mild reaction conditions, easy operation, high regioselectivity and wide substrate scope and provides a novel method for fluorination of quinolines with potential application value.
The C(5) C-H fluorination of 8-aminoqunolines has attracted much attention recently. However, transition-metal catalyst and electrophilic fluorination reagents were required in most of these reactions. Transition-metal catalyst free C(5) C-H nucleophilic fluorination of 8-aminoqunolines was reviewed. This reaction was mediated by a hypervalent iodine reagent and employed cheap, safe and stable silver fluoride as the nucleophilic fluorination reagent. The reaction proceeded without inert gas protection. It possess the merits of simple and mild reaction conditions, easy operation, high regioselectivity and wide substrate scope and provides a novel method for fluorination of quinolines with potential application value.
2020, 40(2): 462-469
doi: 10.6023/cjoc201909005
Abstract:
A synthetic method to prepare 2-benzoylaminobenzoic acids via Pd-catalyzed one-pot oxidation/hydrolysis from 2-alkynyl arylazides is described. The reaction was accomplished in good to excellent yields under mild reaction conditions.
A synthetic method to prepare 2-benzoylaminobenzoic acids via Pd-catalyzed one-pot oxidation/hydrolysis from 2-alkynyl arylazides is described. The reaction was accomplished in good to excellent yields under mild reaction conditions.
2020, 40(2): 470-477
doi: 10.6023/cjoc201905034
Abstract:
An efficient N-heterocyclic carbene (NHC)-catalyzed "Michael-Michael-Lactonization" cascade process involving chalcone derivatives and α-bromoenals for the syntheses of functionalized naphthopyranones was disclosed. This approach was qualified with good yields, readily available starting materials and mild reaction conditions.
An efficient N-heterocyclic carbene (NHC)-catalyzed "Michael-Michael-Lactonization" cascade process involving chalcone derivatives and α-bromoenals for the syntheses of functionalized naphthopyranones was disclosed. This approach was qualified with good yields, readily available starting materials and mild reaction conditions.
2020, 40(2): 478-488
doi: 10.6023/cjoc201907043
Abstract:
A series of novel carbazole-based mono-/bis-carbohydrazone derivatives 3 and 4 were synthesized. Their structures were characterized by 1H NMR, 13C NMR, IR spectra and elemental analysis. The inhibitory activities of all synthesized compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated, and the structure-activity relationship was discussed. The results indicated that most of the compounds had good inhibitory activity against PTP1B, and 1, 5-bis[(9-butyl-3-carba-zolyl)methylene]carbohydrazone (4c) showed the highest inhibitory activity against PTP1B with IC50=(4.81±0.41) μmol/L and the activity was higher than that of the control drug oleanolic acid. Molecular docking and density functional theory (DFT) calculations of 3f and 4c were carried out. The results of molecular docking indicated that 1-[(9-heptyl-3-carbazolyl)meth-ylene]carbohydrazone (3f) and 4c bind to an active site of PTP1B enzyme formed by the helices α3 and α6, and formed a stable complex respectively with PTP1B enzyme by hydrogen bonds, polar, hydrophobic and π-π interactions.
A series of novel carbazole-based mono-/bis-carbohydrazone derivatives 3 and 4 were synthesized. Their structures were characterized by 1H NMR, 13C NMR, IR spectra and elemental analysis. The inhibitory activities of all synthesized compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated, and the structure-activity relationship was discussed. The results indicated that most of the compounds had good inhibitory activity against PTP1B, and 1, 5-bis[(9-butyl-3-carba-zolyl)methylene]carbohydrazone (4c) showed the highest inhibitory activity against PTP1B with IC50=(4.81±0.41) μmol/L and the activity was higher than that of the control drug oleanolic acid. Molecular docking and density functional theory (DFT) calculations of 3f and 4c were carried out. The results of molecular docking indicated that 1-[(9-heptyl-3-carbazolyl)meth-ylene]carbohydrazone (3f) and 4c bind to an active site of PTP1B enzyme formed by the helices α3 and α6, and formed a stable complex respectively with PTP1B enzyme by hydrogen bonds, polar, hydrophobic and π-π interactions.
2020, 40(2): 489-500
doi: 10.6023/cjoc201907035
Abstract:
A new type of pincer palladium complexes C1~C6 based on the strong donor strength of carbazoles skeleton were synthesized. The air-and moisture-stable complexes C1~C6 act as efficient catalysts for the direct arylation of azoles with (hetero)aryl bromides in good to excellent yields with broad substrate scope used KOAc as sole base under aerobic conditions. It was demonstrated that this developed protocol was the most catalytic system for the direct C-H bond arylation for thiazoles under relatively mild reaction conditions at a low catalyst loading of 0.5 mol%.
A new type of pincer palladium complexes C1~C6 based on the strong donor strength of carbazoles skeleton were synthesized. The air-and moisture-stable complexes C1~C6 act as efficient catalysts for the direct arylation of azoles with (hetero)aryl bromides in good to excellent yields with broad substrate scope used KOAc as sole base under aerobic conditions. It was demonstrated that this developed protocol was the most catalytic system for the direct C-H bond arylation for thiazoles under relatively mild reaction conditions at a low catalyst loading of 0.5 mol%.
2020, 40(2): 501-510
doi: 10.6023/cjoc201907033
Abstract:
A series of novel spiro[chromo(2, 3-c)pyrazole-4, 1'-isobenzofuran]-3'-one compounds were synthesized via Knoevenagel condensation and dehydration reaction of 2-(4-dibutylamino-2-hydroxybenzoyl)benzoic acid or 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid with pyrazolones using acid as catalysts and dehydrants. The effects of the ratio of the substrates, catalyst, temperature and reaction time were examined. Their optical properties in different pH and solvent were investigated. It shows that 1-(4-chlorophenyl)-7-(diethylamino)-3-methyl-1H, 3'H-spiro[chromene[2, 3-c]pyrazole-4, 1'-isobenzofuran]-3'-one (1e) and 1-(4-chlorophenyl)-7-(dibutylamino)-3-methyl-1H, 3'H-spiro[chromene[2, 3-c]pyrazole-4, 1'-isobenzofuran]-3'-one (1j) have potential as pH indicators for strong acids and bases.
A series of novel spiro[chromo(2, 3-c)pyrazole-4, 1'-isobenzofuran]-3'-one compounds were synthesized via Knoevenagel condensation and dehydration reaction of 2-(4-dibutylamino-2-hydroxybenzoyl)benzoic acid or 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid with pyrazolones using acid as catalysts and dehydrants. The effects of the ratio of the substrates, catalyst, temperature and reaction time were examined. Their optical properties in different pH and solvent were investigated. It shows that 1-(4-chlorophenyl)-7-(diethylamino)-3-methyl-1H, 3'H-spiro[chromene[2, 3-c]pyrazole-4, 1'-isobenzofuran]-3'-one (1e) and 1-(4-chlorophenyl)-7-(dibutylamino)-3-methyl-1H, 3'H-spiro[chromene[2, 3-c]pyrazole-4, 1'-isobenzofuran]-3'-one (1j) have potential as pH indicators for strong acids and bases.
2020, 40(2): 511-515
doi: 10.6023/cjoc201907048
Abstract:
Peroxynitrite (ONOO-) is an important reactive oxygen species in living organisms, and is associated with various biological process in human body. Using dicyanomethylene-4H-pyran coumarin system, a near-infrared ratiometric fluorescent probe (E)-7-(diethylamino)-3-(2-(dicyanomethylene-4H-pyran)vinyl)-coumarin (DCCM) was developed for ONOO- detec-tion. This probe exhibited a strong response in the presence of ONOO-, with a significant color change from purple to light pink, along with 217 nm fluorescence blue shift. The emission color changed from heliotrope to blue, which enables the monitoring of ONOO- by naked eyes. DCCM was used to sensitively measure ONOO- with low detection limit of 6.0×10-7 mol·L-1. The use of DCCM for imaging ONOO- in HeLa cells was also demonstrated.
Peroxynitrite (ONOO-) is an important reactive oxygen species in living organisms, and is associated with various biological process in human body. Using dicyanomethylene-4H-pyran coumarin system, a near-infrared ratiometric fluorescent probe (E)-7-(diethylamino)-3-(2-(dicyanomethylene-4H-pyran)vinyl)-coumarin (DCCM) was developed for ONOO- detec-tion. This probe exhibited a strong response in the presence of ONOO-, with a significant color change from purple to light pink, along with 217 nm fluorescence blue shift. The emission color changed from heliotrope to blue, which enables the monitoring of ONOO- by naked eyes. DCCM was used to sensitively measure ONOO- with low detection limit of 6.0×10-7 mol·L-1. The use of DCCM for imaging ONOO- in HeLa cells was also demonstrated.
2020, 40(2): 521-527
doi: 10.6023/cjoc201908025
Abstract:
Negamycin is a potent gram-negative antibiotic. By using commercial available ethyl 4-chlorobutyrate as starting material, the formal synthesis of negamycin was achieved within 8 steps and 29% overall yield. This modified synthetic route features in-situ enzymatic promoted asmmetric reduction reaction to introduce chiral hydroxy group at C-5, a late-stage azidination at C-6 to avoid the introduction of explosive azide group in the early stage in previous syntheses. The C-3 aza-chiral center was constructed via Ellman reagent-based asymmetric Mannich reaction. This efficient route is scalable and suitable to establish a library of negamycin analogues for future high-throughput screening.
Negamycin is a potent gram-negative antibiotic. By using commercial available ethyl 4-chlorobutyrate as starting material, the formal synthesis of negamycin was achieved within 8 steps and 29% overall yield. This modified synthetic route features in-situ enzymatic promoted asmmetric reduction reaction to introduce chiral hydroxy group at C-5, a late-stage azidination at C-6 to avoid the introduction of explosive azide group in the early stage in previous syntheses. The C-3 aza-chiral center was constructed via Ellman reagent-based asymmetric Mannich reaction. This efficient route is scalable and suitable to establish a library of negamycin analogues for future high-throughput screening.
2020, 40(2): 528-535
doi: 10.6023/cjoc201907034
Abstract:
In order to find a novel biologically active compound containing aromatic thiazole piperidine structure, 15 novel aryl thiazole piperidine amide derivatives were designed and synthesized. The structures of the target compounds were fully characterized by 1H NMR, 13C NMR and HRMS spectra. The bioactivity test showed that some target compounds had good fungicidal and insecticidal activity. For example, the inhibition rate of 5-(3-bromophenyl)-4-methyl-2-(1-((4-nitrophenyl)-sulfonyl)piperidin-4-yl)thiazole (6b) against Pseudoperonospora cubensis was 100% better than azoxystrobin, and the inhibition rate of 5-(4-bromophenyl)-2-(1-((4-chlorophenyl)sulfonyl)piperidin-4-yl)-4-methylthiazole (6c) against Rhizoctonia solani was 58.86% comparable to azoxystrobin at 200 μg/mL. The lethal rate of (4-(5-(3-bromophenyl)-4-methylthiazol-2-yl) piperidin-1-yl) (m-tolyl)methanone (6h) against Mythimna separata was 100% at 500 μg/mL.
In order to find a novel biologically active compound containing aromatic thiazole piperidine structure, 15 novel aryl thiazole piperidine amide derivatives were designed and synthesized. The structures of the target compounds were fully characterized by 1H NMR, 13C NMR and HRMS spectra. The bioactivity test showed that some target compounds had good fungicidal and insecticidal activity. For example, the inhibition rate of 5-(3-bromophenyl)-4-methyl-2-(1-((4-nitrophenyl)-sulfonyl)piperidin-4-yl)thiazole (6b) against Pseudoperonospora cubensis was 100% better than azoxystrobin, and the inhibition rate of 5-(4-bromophenyl)-2-(1-((4-chlorophenyl)sulfonyl)piperidin-4-yl)-4-methylthiazole (6c) against Rhizoctonia solani was 58.86% comparable to azoxystrobin at 200 μg/mL. The lethal rate of (4-(5-(3-bromophenyl)-4-methylthiazol-2-yl) piperidin-1-yl) (m-tolyl)methanone (6h) against Mythimna separata was 100% at 500 μg/mL.
2020, 40(2): 536-540
doi: 10.6023/cjoc201908015
Abstract:
Anti-cancer drug N-(N'-carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) has been designed based on targeting strategy and a 3-step method has been developed for the synthesis of procarbazine (Pcb). Firstly, 4-methylbenaldehyde, as starting material, was transformed into N-isopropyl-4-methylbenzamide using dibromoisocyanuric acid (DBI). This compound was then directly oxidized to N-isopropyl-4-formylbenzamide by 2-iodoxybenzoic acid (IBX). A reductive amination reaction was then followed leading to Pcb. At last, Pcb was condensed with N-carbobenzoxyglycylproline resulting in Z-GP-Pcb. The overall yield was 49.9%. Furthermore, an in vitro blood-brain barrier (BBB) permeation assay (PAMPA-BBB) was set up to evaluate the permeation activity of Z-GP-Pcb. It was found that the permeation constant (Pe) was (19.22±4.25)×10-6 cm·s-1, which was more than that of the parent drug Pcb[(11.14±1.34))×10-6 cm·s-1]. This evidence suggests that Z-GP-Pcb possesses high activity to penetrate BBB.
Anti-cancer drug N-(N'-carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) has been designed based on targeting strategy and a 3-step method has been developed for the synthesis of procarbazine (Pcb). Firstly, 4-methylbenaldehyde, as starting material, was transformed into N-isopropyl-4-methylbenzamide using dibromoisocyanuric acid (DBI). This compound was then directly oxidized to N-isopropyl-4-formylbenzamide by 2-iodoxybenzoic acid (IBX). A reductive amination reaction was then followed leading to Pcb. At last, Pcb was condensed with N-carbobenzoxyglycylproline resulting in Z-GP-Pcb. The overall yield was 49.9%. Furthermore, an in vitro blood-brain barrier (BBB) permeation assay (PAMPA-BBB) was set up to evaluate the permeation activity of Z-GP-Pcb. It was found that the permeation constant (Pe) was (19.22±4.25)×10-6 cm·s-1, which was more than that of the parent drug Pcb[(11.14±1.34))×10-6 cm·s-1]. This evidence suggests that Z-GP-Pcb possesses high activity to penetrate BBB.
2020, 40(2): 516-520
doi: 10.6023/cjoc201909012
Abstract:
A new kind of organic luminescent materials containing halogen-substituted phthalimide group and carbazole subunit have been conveniently synthesized. They not only showed strong aggregation-induced emission (AIE) effect, but also exhibited thermally activated delayed fluorescence (TADF) in films and crystallization-induced room-temperature phosphorescence (RTP) properties. Especially, RTP with marked afterglow for Br-AI-Cz was observed by naked eye, which could be used as the promising smart materials for the encryption application.
A new kind of organic luminescent materials containing halogen-substituted phthalimide group and carbazole subunit have been conveniently synthesized. They not only showed strong aggregation-induced emission (AIE) effect, but also exhibited thermally activated delayed fluorescence (TADF) in films and crystallization-induced room-temperature phosphorescence (RTP) properties. Especially, RTP with marked afterglow for Br-AI-Cz was observed by naked eye, which could be used as the promising smart materials for the encryption application.
2020, 40(2): 541-542
doi: 10.6023/cjoc202000006
Abstract:
Constructions of Spirocycles Based on Metal-Catalyzed C-H Functionalization/Dearomatization Reaction
2020, 40(2): 543-544
doi: 10.6023/cjoc202000007
Abstract:
2020, 40(2): 545-546
doi: 10.6023/cjoc202000008
Abstract:
2020, 40(2): 547-548
doi: 10.6023/cjoc202000009
Abstract:
2020, 40(2): 549-550
doi: 10.6023/cjoc202000010
Abstract:
