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2019 Volume 39 Issue 9
2019, 39(9): 2345-2364
doi: 10.6023/cjoc201903006
Abstract:
α-Amino acids are the units of proteins, which not only widely occur in many biological important compounds and natural products, but also are useful as organic catalysts or ligands for asymmetric synthesis. Among them, glycines are particularly useful building blocks in organic synthesis. Direct C(sp3)-H bond functionalization of glycine derivatives provided an attractive synthesis strategy for the construction of a variety of α-substituted α-amino acids. The recent progress in the α-C(sp3)-H bond activation of glycine derivatives, with various reagents to form carbon-carbon and carbon-heteroatom bond, and oxidative coupling/cyclization reaction involving glycine derivatives is reviewed.
α-Amino acids are the units of proteins, which not only widely occur in many biological important compounds and natural products, but also are useful as organic catalysts or ligands for asymmetric synthesis. Among them, glycines are particularly useful building blocks in organic synthesis. Direct C(sp3)-H bond functionalization of glycine derivatives provided an attractive synthesis strategy for the construction of a variety of α-substituted α-amino acids. The recent progress in the α-C(sp3)-H bond activation of glycine derivatives, with various reagents to form carbon-carbon and carbon-heteroatom bond, and oxidative coupling/cyclization reaction involving glycine derivatives is reviewed.
2019, 39(9): 2365-2378
doi: 10.6023/cjoc201903041
Abstract:
The development of highly efficient and selective synthetic methodologies is an important research task in organic chemistry. In recent years, the Huisgen zwitterions, a type of intermediates derived from nucleophilic addition of tertiary phosphine to azodicarboxylates, have shown unique superiority and efficiency in synthesis of azacyclic compounds, and therefore have attracted broad interest from organic chemists. A large number of annulation reactions based on Huisgen zwitterions have been reported. According to the types of electrophiles, the annulation reactions of Husigen zwitterions with carbonyl compounds, electron-deficient alkenes, imines, and other electrophiles are summarized, respectively.
The development of highly efficient and selective synthetic methodologies is an important research task in organic chemistry. In recent years, the Huisgen zwitterions, a type of intermediates derived from nucleophilic addition of tertiary phosphine to azodicarboxylates, have shown unique superiority and efficiency in synthesis of azacyclic compounds, and therefore have attracted broad interest from organic chemists. A large number of annulation reactions based on Huisgen zwitterions have been reported. According to the types of electrophiles, the annulation reactions of Husigen zwitterions with carbonyl compounds, electron-deficient alkenes, imines, and other electrophiles are summarized, respectively.
2019, 39(9): 2379-2391
doi: 10.6023/cjoc201903038
Abstract:
Synthetic glycopolypeptides, as analogues of natural glycoproteins, are an emerging class of bioinspired polymers with excellent biocompatibility. They can mimic the structure and functions of natural glycoproteins, and show great potential for biological applications, such as biomolecular recognition, drug/gene delivery, cell adhesion and targeting, as well as cell culture and tissue engineering. Nevertheless, the efficient and lab/pilot scale preparation of well-defined and tunable glycopolypeptides with complex polymer structures, has been a challenging field until now. The fast development of "Click" chemistry/reaction offers versatile and powerful tools for the synthesis of glycopolypeptides. The state of arts for the development of new "Click" synthetic strategies and methods in the preparation of glycopolypeptides, mainly including post-polymerization glycosylation of synthetic polypeptides and ring-opening polymerization of glycosylated N-carboxyanhydride (glyco-NCA) is reviewed. The pros and cons of current developments for the synthesis of glycopolypeptide analogues and their future perspectives are also stated and discussed.
Synthetic glycopolypeptides, as analogues of natural glycoproteins, are an emerging class of bioinspired polymers with excellent biocompatibility. They can mimic the structure and functions of natural glycoproteins, and show great potential for biological applications, such as biomolecular recognition, drug/gene delivery, cell adhesion and targeting, as well as cell culture and tissue engineering. Nevertheless, the efficient and lab/pilot scale preparation of well-defined and tunable glycopolypeptides with complex polymer structures, has been a challenging field until now. The fast development of "Click" chemistry/reaction offers versatile and powerful tools for the synthesis of glycopolypeptides. The state of arts for the development of new "Click" synthetic strategies and methods in the preparation of glycopolypeptides, mainly including post-polymerization glycosylation of synthetic polypeptides and ring-opening polymerization of glycosylated N-carboxyanhydride (glyco-NCA) is reviewed. The pros and cons of current developments for the synthesis of glycopolypeptide analogues and their future perspectives are also stated and discussed.
2019, 39(9): 2392-2402
doi: 10.6023/cjoc201903025
Abstract:
2, 3-Dihydroquinazolin-4(1H)-one compounds are an important class of nitrogen-containing fused heterocycles, which possess a wide range of pharmacological and biological activities and have important applications in the fields of synthesis and research & development of drugs. Therefore, its synthetic methods have also attracted considerable attention. In this paper, the main advances in the synthesis of 2, 3-dihydroquinazolin-4(1H)-ones and their proposed reaction mechanisms from the raw materials such as o-aminobenzamides, isatoic anhydrides, o-nitrobenzamides, o-azidobenzamide, o-bromo-benzamide, o-bromobenzonitrile, o-aminobenzoic acids, o-aminobenzonitrile, o-amino-N-(propa-1, 2-dienyl)benzamides, and N-alkyl anilines were introduced and reviewed, respectively. Finally, the synthesis of these compounds was summarized and the prospect of their development was prospected.
2, 3-Dihydroquinazolin-4(1H)-one compounds are an important class of nitrogen-containing fused heterocycles, which possess a wide range of pharmacological and biological activities and have important applications in the fields of synthesis and research & development of drugs. Therefore, its synthetic methods have also attracted considerable attention. In this paper, the main advances in the synthesis of 2, 3-dihydroquinazolin-4(1H)-ones and their proposed reaction mechanisms from the raw materials such as o-aminobenzamides, isatoic anhydrides, o-nitrobenzamides, o-azidobenzamide, o-bromo-benzamide, o-bromobenzonitrile, o-aminobenzoic acids, o-aminobenzonitrile, o-amino-N-(propa-1, 2-dienyl)benzamides, and N-alkyl anilines were introduced and reviewed, respectively. Finally, the synthesis of these compounds was summarized and the prospect of their development was prospected.
2019, 39(9): 2403-2411
doi: 10.6023/cjoc201901027
Abstract:
β-Ketophosphine oxides are extremely important phosphorus-containing compounds and widely utilitied in the field of organic synthesis chemistry. Developing simple, green and efficient protocol to synthesize β-ketophosphine oxides has attracted great attention of chemists in recent years. The recent advances on the synthesis of β-ketophosphine oxides via phosphorus-centered radical addition reaction or hydration reaction are summarized.
β-Ketophosphine oxides are extremely important phosphorus-containing compounds and widely utilitied in the field of organic synthesis chemistry. Developing simple, green and efficient protocol to synthesize β-ketophosphine oxides has attracted great attention of chemists in recent years. The recent advances on the synthesis of β-ketophosphine oxides via phosphorus-centered radical addition reaction or hydration reaction are summarized.
2019, 39(9): 2412-2427
doi: 10.6023/cjoc201902012
Abstract:
Maleimide, a common motif in a variety of natural alkaloids, has been extensively investigated due to its noteworthy biological activities and optical properties. Additionally, it can be transformed into many important heterocyclic frameworks such as succinimides, pyrrolidines, and 2-pyrrolidones. Thus, a great deal of attention has been focused on the development of new synthetic routes to access polyfunctionalized maleimides. In this article, the recent research progress in functionalization of double bond is reviewed based on maleimides according to Michael addition, oxidative coupling and cycloaddition reaction.
Maleimide, a common motif in a variety of natural alkaloids, has been extensively investigated due to its noteworthy biological activities and optical properties. Additionally, it can be transformed into many important heterocyclic frameworks such as succinimides, pyrrolidines, and 2-pyrrolidones. Thus, a great deal of attention has been focused on the development of new synthetic routes to access polyfunctionalized maleimides. In this article, the recent research progress in functionalization of double bond is reviewed based on maleimides according to Michael addition, oxidative coupling and cycloaddition reaction.
2019, 39(9): 2428-2442
doi: 10.6023/cjoc201901031
Abstract:
N-Benzyl is a common protecting group for organic amines, owing to its convenient and efficient removal. It plays an important role in organic synthesis, especially in the research of drugs and natural products. In recent years, a large number of researchers have conducted extensive studies on N-benzyl deprotection, but the related work is scattered and lacks systematic review. Therefore, the progress of N-benzyl removal is systematically and comprehensively summarized from the aspects of reductive, oxidative and acid-base debenzylation.
N-Benzyl is a common protecting group for organic amines, owing to its convenient and efficient removal. It plays an important role in organic synthesis, especially in the research of drugs and natural products. In recent years, a large number of researchers have conducted extensive studies on N-benzyl deprotection, but the related work is scattered and lacks systematic review. Therefore, the progress of N-benzyl removal is systematically and comprehensively summarized from the aspects of reductive, oxidative and acid-base debenzylation.
2019, 39(9): 2443-2457
doi: 10.6023/cjoc201901028
Abstract:
As one of the most important transformations in organic synthesis, deoxygenation reduction of sulfoxides to thioethers has attracted wide attention in researches and applications. With the development of organicmetallic chemistry, many mild and practical methods have been developed to reduce sulfoxides. In this review, based on the types of the reducing agents, the research progress on the deoxygenation reduction of sulfoxides to thiothers in recent 20 years is summarized. In addition, the advantages and disadvantages of these reduction systems, some reaction mechanisms and the prospects of research in this field are discussed.
As one of the most important transformations in organic synthesis, deoxygenation reduction of sulfoxides to thioethers has attracted wide attention in researches and applications. With the development of organicmetallic chemistry, many mild and practical methods have been developed to reduce sulfoxides. In this review, based on the types of the reducing agents, the research progress on the deoxygenation reduction of sulfoxides to thiothers in recent 20 years is summarized. In addition, the advantages and disadvantages of these reduction systems, some reaction mechanisms and the prospects of research in this field are discussed.
2019, 39(9): 2458-2466
doi: 10.6023/cjoc201902032
Abstract:
It is extremely urgent to develop green energy and find alternatives to fossil fuels since the energy shortage and environmental pollution become the worldwide concern. Methanol has emerged as a promising carrier for hydrogen storage owing to its high hydrogen density, simple structure and environmental friendly substance. The methanol reforming has triggered great efforts on the development of homogeneous catalysts, and the aim is to decrease methanol dehydrogenation reaction temperature and improve the selectivity. This review summarizes the recent research progresses in the homogeneously transition-metal catalyzed thermal dehydrogenation of methanol and aqueous methanol reforming. It mainly focuses on the structural characteristics of Ru, Rh, Ir, Fe and Mn-based complexes, catalytic reaction conditions, the reaction yield, and the catalytic reaction mechanism. The differences in the reactivities of these catalysts are analyzed and compared. Not only a summary is given, but also some perspectives and inspiration for improving the performance of aqueous methanol reforming catalysts for future research are discussed.
It is extremely urgent to develop green energy and find alternatives to fossil fuels since the energy shortage and environmental pollution become the worldwide concern. Methanol has emerged as a promising carrier for hydrogen storage owing to its high hydrogen density, simple structure and environmental friendly substance. The methanol reforming has triggered great efforts on the development of homogeneous catalysts, and the aim is to decrease methanol dehydrogenation reaction temperature and improve the selectivity. This review summarizes the recent research progresses in the homogeneously transition-metal catalyzed thermal dehydrogenation of methanol and aqueous methanol reforming. It mainly focuses on the structural characteristics of Ru, Rh, Ir, Fe and Mn-based complexes, catalytic reaction conditions, the reaction yield, and the catalytic reaction mechanism. The differences in the reactivities of these catalysts are analyzed and compared. Not only a summary is given, but also some perspectives and inspiration for improving the performance of aqueous methanol reforming catalysts for future research are discussed.
2019, 39(9): 2467-2484
doi: 10.6023/cjoc201901024
Abstract:
Small molecules (biological small molecules) in vivo are not only in a large number, involving inorganic small molecules, such as SO2, H2S, NO and CO, and more organic small molecules, such as monosaccharides, oligosaccharides, hormones, coenzymes, glycerol, stimulating factors, regulatory factors, Vitamins, etc., moreover, play an important role in pathology, physiology, and so on. Therefore, it is necessary to observe and monitor small molecules in vivo in real time, and the two-photon fluorescence probe is a necessary tool to achieve this goal. The advantages of two-photon fluorescence probe, such as fixed target (very small dot) excitation, high horizontal and vertical resolution, no photobleaching, no phototoxicity and deep imaging in tissues, and so on, demonstrate its unparalleled superiority. It can be used for dynamic 3D observation and monitoring of biological small molecules in cells or tissues. In this paper, CO, monosaccharide (glucose, β-galactosidase), SO2, H2S, NO, peroxy (sulfur) compounds, mercaptan/thiophenol, 1O2, formaldehyde, HNO, HclO, O2·- and ONOO- two-photon fluorescence probes which have been developed in recent 5 years were reviewed. The sensing mechanisms of these two-photon fluorescence probes were systematically analyzed, and the development and prospect of two-photon fluorescence probes for small biomolecules are prospected.
Small molecules (biological small molecules) in vivo are not only in a large number, involving inorganic small molecules, such as SO2, H2S, NO and CO, and more organic small molecules, such as monosaccharides, oligosaccharides, hormones, coenzymes, glycerol, stimulating factors, regulatory factors, Vitamins, etc., moreover, play an important role in pathology, physiology, and so on. Therefore, it is necessary to observe and monitor small molecules in vivo in real time, and the two-photon fluorescence probe is a necessary tool to achieve this goal. The advantages of two-photon fluorescence probe, such as fixed target (very small dot) excitation, high horizontal and vertical resolution, no photobleaching, no phototoxicity and deep imaging in tissues, and so on, demonstrate its unparalleled superiority. It can be used for dynamic 3D observation and monitoring of biological small molecules in cells or tissues. In this paper, CO, monosaccharide (glucose, β-galactosidase), SO2, H2S, NO, peroxy (sulfur) compounds, mercaptan/thiophenol, 1O2, formaldehyde, HNO, HclO, O2·- and ONOO- two-photon fluorescence probes which have been developed in recent 5 years were reviewed. The sensing mechanisms of these two-photon fluorescence probes were systematically analyzed, and the development and prospect of two-photon fluorescence probes for small biomolecules are prospected.
2019, 39(9): 2485-2491
doi: 10.6023/cjoc201903010
Abstract:
A novel fluorescent sensor L based on 8-hydroxyquinoline (8-HQ) has been designed and synthesized. The sensor L displayed excellent sensitivity specific toward Cd2+ and pyrophosphate anion (PPi), respectively. The fluorescence emission peak at 537 nm was quenched when Cd2+ was added to the DMSO/H2O (V/V=1/1, 0.01 mol/L, Hepes-HCl buffer, pH=7.20) solution of sensor L and the detection limit was as low as 5.87×10-8 mol/L. The 1:1 stoichiometry was verified by Job's plot and mass spectrum, and the association constant was obtained to be 4.37×104 L/mol. The further study found that the L-Cd2+ system has high selectivity for detection of PPi by ligand replacement method and L could be used as a logic gate fluorescence sensor. In addition, the sensor L was employed for imaging the Cd2+ and PPi in living cells.
A novel fluorescent sensor L based on 8-hydroxyquinoline (8-HQ) has been designed and synthesized. The sensor L displayed excellent sensitivity specific toward Cd2+ and pyrophosphate anion (PPi), respectively. The fluorescence emission peak at 537 nm was quenched when Cd2+ was added to the DMSO/H2O (V/V=1/1, 0.01 mol/L, Hepes-HCl buffer, pH=7.20) solution of sensor L and the detection limit was as low as 5.87×10-8 mol/L. The 1:1 stoichiometry was verified by Job's plot and mass spectrum, and the association constant was obtained to be 4.37×104 L/mol. The further study found that the L-Cd2+ system has high selectivity for detection of PPi by ligand replacement method and L could be used as a logic gate fluorescence sensor. In addition, the sensor L was employed for imaging the Cd2+ and PPi in living cells.
2019, 39(9): 2499-2506
doi: 10.6023/cjoc201903052
Abstract:
The electro-oxidation cyanation of p-methoxybenzyl alcohol (p-MeOC6H4CH2OH) to prepare aryl nitriles was studied by using cyclic voltammetry (CV) and constant current electrolysis (CCE). The effects of the volume ratio of H2O, concentration of H2SO4, temperature, electrode materials, current density and solvents on the electro-chemical reaction were studied. The results showed that the yield of p-methoxylbenzonitrile (p-MeOBN) was 90% in 0.15 mol·L-1 H2SO4 and 30% H2O-DMSO solution at 60℃ and 10 mA/cm2 of current density when tetrabutylammonium perchlorate (Bu4NClO4) was used as electrolyte. The CCE of aromatic benzyl alcohols with different p-and o-substituted analogs was investigated under the optimized reaction conditions, and the yields toward formation of the corresponding aryl nitriles were 61%~92%. A plausible mechanism for the electro-oxidation cyanation procedure was proposed. A novel paired electrochemical method for the synthesis of aryl nitriles from aromatic benzyl alcohols with hydroxylamine (HAM) as "N" source and aldehyde in situ in undivided electrochemical cell was successfully developed.
The electro-oxidation cyanation of p-methoxybenzyl alcohol (p-MeOC6H4CH2OH) to prepare aryl nitriles was studied by using cyclic voltammetry (CV) and constant current electrolysis (CCE). The effects of the volume ratio of H2O, concentration of H2SO4, temperature, electrode materials, current density and solvents on the electro-chemical reaction were studied. The results showed that the yield of p-methoxylbenzonitrile (p-MeOBN) was 90% in 0.15 mol·L-1 H2SO4 and 30% H2O-DMSO solution at 60℃ and 10 mA/cm2 of current density when tetrabutylammonium perchlorate (Bu4NClO4) was used as electrolyte. The CCE of aromatic benzyl alcohols with different p-and o-substituted analogs was investigated under the optimized reaction conditions, and the yields toward formation of the corresponding aryl nitriles were 61%~92%. A plausible mechanism for the electro-oxidation cyanation procedure was proposed. A novel paired electrochemical method for the synthesis of aryl nitriles from aromatic benzyl alcohols with hydroxylamine (HAM) as "N" source and aldehyde in situ in undivided electrochemical cell was successfully developed.
2019, 39(9): 2525-2533
doi: 10.6023/cjoc201903034
Abstract:
Two heterocyclic compounds 12H-chromeno[2, 3-b]quinolin-12-one and 6H-chromeno[4, 3-b]quinolin-6-one could be synthesized by the reaction of anthranil with 4-hydroxycoumarin under high temperature conditions. The reaction is a thermo-promoted transformation, without the assistance of catalysts or additives, and without the generation of toxic wastes. This one-step reaction is superior to other reported methods for the preparation of such heterocycles.
Two heterocyclic compounds 12H-chromeno[2, 3-b]quinolin-12-one and 6H-chromeno[4, 3-b]quinolin-6-one could be synthesized by the reaction of anthranil with 4-hydroxycoumarin under high temperature conditions. The reaction is a thermo-promoted transformation, without the assistance of catalysts or additives, and without the generation of toxic wastes. This one-step reaction is superior to other reported methods for the preparation of such heterocycles.
2019, 39(9): 2534-2540
doi: 10.6023/cjoc201902035
Abstract:
Two thiazolo[5, 4-b]carbazole based blue fluorescent materials, namely TCz-PCz and TCz-TPA, were synthesized by palladium catalyzed C-C and C-N coupling reactions, and their structures were confirmed by 1H NMR, 13C NMR, mass spectrometry and elemental analysis. The thermal, photophysical, and electrochemical properties of these materials were fully investigated. The results indicate that these compounds possess thermal and amorphous stabilities with decomposition temperature up to 400℃ and glass transition temperatures of 119℃. Both TCz-PCz and TCz-TPA show strong blue emission in solution with high fluorescent quantum yields of 71% and 73%, respectively. These molecules show high HOMO energy levels of -5.41 and -5.21 eV that are favorable for hole injection and transportation from hole-transporting layer to the emitting layer in devices. The non-doped blue OLED using TCz-PCz as emitter through vacuum evaporation was fabricated for purpose of investigating its electroluminescence properties. The device exhibited stable blue electroluminescence, a low turn-on voltage of 3.1 V, a maximum luminance of 2190 cd·m-2, and a maximum current efficiency of 2.88 cd·A-1 were achieved, respectively.
Two thiazolo[5, 4-b]carbazole based blue fluorescent materials, namely TCz-PCz and TCz-TPA, were synthesized by palladium catalyzed C-C and C-N coupling reactions, and their structures were confirmed by 1H NMR, 13C NMR, mass spectrometry and elemental analysis. The thermal, photophysical, and electrochemical properties of these materials were fully investigated. The results indicate that these compounds possess thermal and amorphous stabilities with decomposition temperature up to 400℃ and glass transition temperatures of 119℃. Both TCz-PCz and TCz-TPA show strong blue emission in solution with high fluorescent quantum yields of 71% and 73%, respectively. These molecules show high HOMO energy levels of -5.41 and -5.21 eV that are favorable for hole injection and transportation from hole-transporting layer to the emitting layer in devices. The non-doped blue OLED using TCz-PCz as emitter through vacuum evaporation was fabricated for purpose of investigating its electroluminescence properties. The device exhibited stable blue electroluminescence, a low turn-on voltage of 3.1 V, a maximum luminance of 2190 cd·m-2, and a maximum current efficiency of 2.88 cd·A-1 were achieved, respectively.
2019, 39(9): 2549-2559
doi: 10.6023/cjoc201902003
Abstract:
Thiazolones underwent formal[2+1] annulation with stable sulfur ylide to construct cyclopropane-fused spiro-thiazolone derivatives in 30%~99% yields with good diastereoselectivity.
Thiazolones underwent formal[2+1] annulation with stable sulfur ylide to construct cyclopropane-fused spiro-thiazolone derivatives in 30%~99% yields with good diastereoselectivity.
2019, 39(9): 2567-2573
doi: 10.6023/cjoc201903071
Abstract:
Camptothecin derivatives exist mainly as inactive open ring carboxylates in physiological media. Tumor microenvironment is generally weakly acidic, whereas supramolecular organic frameworks can adsorb and deliver anionic antitumor drugs into tumor cells. In principle, supramolecular organic frameworks (SOFs) can adsorb and deliver camptothecin open ring carboxylates to tumor microenvironment and the delivered carboxylates can undergo lactonization to afford active molecules due to the weak acid character of the tumor microenvironment, which may lead to efficient utilization of the carboxylates as predrugs. To explore this potential, dialysis experiments for the open ring carboxylates of camptothecin, SN-38 and 10-hydroxycamptothecin in the presence of two SOFs were conducted, which revealed important adsorption and retaining capacity of the SOFs for the carboxylates. Absorption spectroscopy was also utilized to evaluate the lactonization kinetics of the three carboxylates in weakly acidic saline solution. The result reveals that at pH=6.5, the half lives of the conversion are 120, 22 and 31 h, respectively, which are considerably shorter than the time gap for repeated administrations of clinically used irinotican (14 d) or topotecan (21 d), which provides the experimental basis for further study.
Camptothecin derivatives exist mainly as inactive open ring carboxylates in physiological media. Tumor microenvironment is generally weakly acidic, whereas supramolecular organic frameworks can adsorb and deliver anionic antitumor drugs into tumor cells. In principle, supramolecular organic frameworks (SOFs) can adsorb and deliver camptothecin open ring carboxylates to tumor microenvironment and the delivered carboxylates can undergo lactonization to afford active molecules due to the weak acid character of the tumor microenvironment, which may lead to efficient utilization of the carboxylates as predrugs. To explore this potential, dialysis experiments for the open ring carboxylates of camptothecin, SN-38 and 10-hydroxycamptothecin in the presence of two SOFs were conducted, which revealed important adsorption and retaining capacity of the SOFs for the carboxylates. Absorption spectroscopy was also utilized to evaluate the lactonization kinetics of the three carboxylates in weakly acidic saline solution. The result reveals that at pH=6.5, the half lives of the conversion are 120, 22 and 31 h, respectively, which are considerably shorter than the time gap for repeated administrations of clinically used irinotican (14 d) or topotecan (21 d), which provides the experimental basis for further study.
2019, 39(9): 2574-2580
doi: 10.6023/cjoc201901016
Abstract:
In this paper, 18 novel chrysin derivatives were designed and synthesized. All target compounds were tested for anti-Toxoplasma activity by methyl thiazolyl tetrazolium (MTT) colorimetric method. The chemical structures were characterized by 1H NMR, 13C NMR and HRMS spectra. The selectivity index of 5-hydroxy-7-methoxy-4-oxo-N, 2-diphenyl-4H-chro-mene-8-sulfonamide (D2) was 1.76, indicating that the anti-toxoplasma activity of compound D2 was significantly higher than that of the lead compound chrysin and the positive control drug sulfadiazine.
In this paper, 18 novel chrysin derivatives were designed and synthesized. All target compounds were tested for anti-Toxoplasma activity by methyl thiazolyl tetrazolium (MTT) colorimetric method. The chemical structures were characterized by 1H NMR, 13C NMR and HRMS spectra. The selectivity index of 5-hydroxy-7-methoxy-4-oxo-N, 2-diphenyl-4H-chro-mene-8-sulfonamide (D2) was 1.76, indicating that the anti-toxoplasma activity of compound D2 was significantly higher than that of the lead compound chrysin and the positive control drug sulfadiazine.
2019, 39(9): 2589-2598
doi: 10.6023/cjoc201902023
Abstract:
Three organic dyes with dendritic and 3D triphenylamine derivatives as the donor unit, benzoic acid as the acceptor unit and benzothiadiazole (BT) or difluorobenzothiadiazole (DFBT) as the second acceptor were designed and synthesized. The influences of different donors and second acceptors on the photophysical, electrochemical and photovoltaic properties of dye-sensitizers were systematically investigated. The organic dye with dendritic triphenylamine derivative as a donor unit possesses a higher molar absorption coefficient, and the organic dye with 3D triphenylamine derivative (IDTTPA) as a donor unit has a broader absorption spectrum. The dye-sensitized solar cells based on three organic dyes achieved power conversion efficiencies of 5.27%, 4.22% and 5.50%, respectively. After optimizing the battery with 1 mmol·L-1 co-adsorbent chenodeoxycholic acid (CDCA), the power conversion efficiencies of the organic dyes were increased to 5.46%, 4.98% and 6.26%, respectively.
Three organic dyes with dendritic and 3D triphenylamine derivatives as the donor unit, benzoic acid as the acceptor unit and benzothiadiazole (BT) or difluorobenzothiadiazole (DFBT) as the second acceptor were designed and synthesized. The influences of different donors and second acceptors on the photophysical, electrochemical and photovoltaic properties of dye-sensitizers were systematically investigated. The organic dye with dendritic triphenylamine derivative as a donor unit possesses a higher molar absorption coefficient, and the organic dye with 3D triphenylamine derivative (IDTTPA) as a donor unit has a broader absorption spectrum. The dye-sensitized solar cells based on three organic dyes achieved power conversion efficiencies of 5.27%, 4.22% and 5.50%, respectively. After optimizing the battery with 1 mmol·L-1 co-adsorbent chenodeoxycholic acid (CDCA), the power conversion efficiencies of the organic dyes were increased to 5.46%, 4.98% and 6.26%, respectively.
2019, 39(9): 2599-2608
doi: 10.6023/cjoc201901013
Abstract:
A series of novel 2, 5-disubstituted-1, 3, 4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP). The structure-activity relationship was discussed. The results showed that most of compounds had good inhibitory activity against PTP1B over the highly homologous TCPTP, and 2-(9-carbazolylmethylene)-5-(3-chlorobenzoylamino)-1, 3, 4-thiadiazole (5c) displayed the highest inhibitory activity against PTP1B[IC50=(2.43±0.43) μg/mL]. The inhibitory activities of 2-(9-carbazolylmethylene)-5-(4-methylbenzoylamino)-1, 3, 4-thiadiazole (5b) and 5c against PTP1B were higher than that of positive control oleanolic acid. Molecular docking and density functional theory (DFT) calculations of the target compound 5c were performed. The docking result showed that compound 5c and PTP1B enzyme formed a stable complex by hydrogen bonds, hydrophobic and π-π interactions.
A series of novel 2, 5-disubstituted-1, 3, 4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP). The structure-activity relationship was discussed. The results showed that most of compounds had good inhibitory activity against PTP1B over the highly homologous TCPTP, and 2-(9-carbazolylmethylene)-5-(3-chlorobenzoylamino)-1, 3, 4-thiadiazole (5c) displayed the highest inhibitory activity against PTP1B[IC50=(2.43±0.43) μg/mL]. The inhibitory activities of 2-(9-carbazolylmethylene)-5-(4-methylbenzoylamino)-1, 3, 4-thiadiazole (5b) and 5c against PTP1B were higher than that of positive control oleanolic acid. Molecular docking and density functional theory (DFT) calculations of the target compound 5c were performed. The docking result showed that compound 5c and PTP1B enzyme formed a stable complex by hydrogen bonds, hydrophobic and π-π interactions.
2019, 39(9): 2609-2615
doi: 10.6023/cjoc201901045
Abstract:
An improved route for the total synthesis of iso-L-guanosine was developed. Using L-ribose as the starting material, 3, 5-O-dibenzyl-1-deoxy-L-ribose was firstly synthesized. Then, Mitsunobu reaction between N2, N2-bis(tert-butyloxycarbonyl)-6-chloro-guanine and 3, 5-O-dibenzyl-1-deoxy-L-ribose afforded isonucleoside 6. Finally, iso-L-guanosine was synthesized in 9 steps with 37.3% overall yield. Adopting Mitsunobu reaction as the key step, it has the merits of high steroseletivity and regioselectivity, mild reaction condition, and high yield. Currently developed approach could be used as a general synthetic strategy for the synthesis other related guanine isonucleosides.
An improved route for the total synthesis of iso-L-guanosine was developed. Using L-ribose as the starting material, 3, 5-O-dibenzyl-1-deoxy-L-ribose was firstly synthesized. Then, Mitsunobu reaction between N2, N2-bis(tert-butyloxycarbonyl)-6-chloro-guanine and 3, 5-O-dibenzyl-1-deoxy-L-ribose afforded isonucleoside 6. Finally, iso-L-guanosine was synthesized in 9 steps with 37.3% overall yield. Adopting Mitsunobu reaction as the key step, it has the merits of high steroseletivity and regioselectivity, mild reaction condition, and high yield. Currently developed approach could be used as a general synthetic strategy for the synthesis other related guanine isonucleosides.
Design, Synthesis and Antioxidant Application of Camphorsulfonic Acid Thiazolylhydrazone Derivatives
2019, 39(9): 2616-2624
doi: 10.6023/cjoc201901053
Abstract:
A series of camphorsulfonic acid thiazolylhydrazone derivatives were synthesized by using camphorsulfonic acid derivated from natural camphor as the starting material in three steps, including condensation with aminothiourea and cyclization with bromoacetophenone. Their structures were characterized by 1H NMR, 13C NMR and HR-MS, and their antioxidant activities were also investigated. The results showed that these compounds had good antioxidant activities compared with the positive control trolox. Among of them, (2-(2-(4-(4-cyanophenyl)thiazol-2-yl)indenyl)-7, 7-dimethylbicyclo-[2.2.1]hept-1-yl)methanesulfonic acid (Q19) exhibited the relatively strong 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with IC50 value of 176 μmol/L, (2-(2-(4-(4-fluorophenyl)thiazol-2-yl)hydrazino)-7, 7-dimethylbicyclo-[2.2.1]hept-1-yl)methanesulfonic acid (Q3) exhibited the relatively strong diammonium 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging activity with IC50 value of 20.6 μmol/L, (E)-(7, 7-dimethyl-2-(2-(4-(3-methyl)-thiazol-2-yl)indenyl)bicyclo[2.2.1]hept-1-yl)-sulfonic acid (Q8) exhibited the strong hydroxyl radical scavenging activity with scavenge rate 66.2%, (2-(2-(4-(4-biphenyl)thiazol-2-yl)indenyl)-7, 7-dimethylbicyclo[2.2.1]hept-1-yl)methane-sulfonic acid (Q20) exhibited the relatively strong superoxide radical scavenging activity with IC50 value of 20.7 μmol/L. Compared with the positive control kojic acid, (2-(2-(4-(2-hydroxyphenyl)thiazol-2-yl)arylene)-7, 7-dimethylbicyclo[2.2.1]hept-1-yl)methanesulfonic acid (Q16) exhibited remarkable tyrosinase inhibitory activity with IC50 value of 154.9 μmol/L. It was known from the structure-activity relationship that the structure of R gave great influence on the activities of thiazolylhydrazone derivatives.
A series of camphorsulfonic acid thiazolylhydrazone derivatives were synthesized by using camphorsulfonic acid derivated from natural camphor as the starting material in three steps, including condensation with aminothiourea and cyclization with bromoacetophenone. Their structures were characterized by 1H NMR, 13C NMR and HR-MS, and their antioxidant activities were also investigated. The results showed that these compounds had good antioxidant activities compared with the positive control trolox. Among of them, (2-(2-(4-(4-cyanophenyl)thiazol-2-yl)indenyl)-7, 7-dimethylbicyclo-[2.2.1]hept-1-yl)methanesulfonic acid (Q19) exhibited the relatively strong 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with IC50 value of 176 μmol/L, (2-(2-(4-(4-fluorophenyl)thiazol-2-yl)hydrazino)-7, 7-dimethylbicyclo-[2.2.1]hept-1-yl)methanesulfonic acid (Q3) exhibited the relatively strong diammonium 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging activity with IC50 value of 20.6 μmol/L, (E)-(7, 7-dimethyl-2-(2-(4-(3-methyl)-thiazol-2-yl)indenyl)bicyclo[2.2.1]hept-1-yl)-sulfonic acid (Q8) exhibited the strong hydroxyl radical scavenging activity with scavenge rate 66.2%, (2-(2-(4-(4-biphenyl)thiazol-2-yl)indenyl)-7, 7-dimethylbicyclo[2.2.1]hept-1-yl)methane-sulfonic acid (Q20) exhibited the relatively strong superoxide radical scavenging activity with IC50 value of 20.7 μmol/L. Compared with the positive control kojic acid, (2-(2-(4-(2-hydroxyphenyl)thiazol-2-yl)arylene)-7, 7-dimethylbicyclo[2.2.1]hept-1-yl)methanesulfonic acid (Q16) exhibited remarkable tyrosinase inhibitory activity with IC50 value of 154.9 μmol/L. It was known from the structure-activity relationship that the structure of R gave great influence on the activities of thiazolylhydrazone derivatives.
2019, 39(9): 2625-2631
doi: 10.6023/cjoc201901039
Abstract:
Alzheimer's Disease (AD) is one of the major health crises in the 21st century, and due to the complexity of its pathogenesis, there has no good solution to cure this disease. In order to find more economical and effective drugs for the treatment of neurodegenerative diseases, a series of novel 2-dehydroepiandrosterone benzathine derivatives were synthesized and their activity on the NO release of microglia cell line BV-2 activated by lipopolysaccharide (LPS), as well as their effect on cell viability were studied. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and HRMS. The results showed that all compounds had inhibitory effects on the NO release of LPS-activated mouse microglial cell line BV2 after 24 h of treatment, and it was dose-dependent. In particular, the IC50 values of 2-(3-chloro)benzylidene-15β, 16β-methylene-androstane-4, 6-diene-3, 17-dione (5a) and 2-(3, 4, 5-trimethoxy)benzylidene-15β, 16β-methylene-androstane-4, 6-die-ne-3, 17-dione (5j) were 2.69 and 3.28 μmol·L-1, respectively, which were better than the positive control Minocycline. The results showed that these compounds may be effective in the development of neurodegenerative diseases involving activation of microglia, and the mechanism deserved further study.
Alzheimer's Disease (AD) is one of the major health crises in the 21st century, and due to the complexity of its pathogenesis, there has no good solution to cure this disease. In order to find more economical and effective drugs for the treatment of neurodegenerative diseases, a series of novel 2-dehydroepiandrosterone benzathine derivatives were synthesized and their activity on the NO release of microglia cell line BV-2 activated by lipopolysaccharide (LPS), as well as their effect on cell viability were studied. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and HRMS. The results showed that all compounds had inhibitory effects on the NO release of LPS-activated mouse microglial cell line BV2 after 24 h of treatment, and it was dose-dependent. In particular, the IC50 values of 2-(3-chloro)benzylidene-15β, 16β-methylene-androstane-4, 6-diene-3, 17-dione (5a) and 2-(3, 4, 5-trimethoxy)benzylidene-15β, 16β-methylene-androstane-4, 6-die-ne-3, 17-dione (5j) were 2.69 and 3.28 μmol·L-1, respectively, which were better than the positive control Minocycline. The results showed that these compounds may be effective in the development of neurodegenerative diseases involving activation of microglia, and the mechanism deserved further study.
2019, 39(9): 2639-2644
doi: 10.6023/cjoc201812048
Abstract:
A novel hydrophobic polycarbonate containing perfluorocyclobutyl (PFCB) aryl ether was synthesized from commercially available p-methoxyphenol. The polymer exhibited excellent thermal stability and hydrophobicity without reducing the transparency of the material. The thermal decomposition temperature was 351℃ and the contact angle between the film and water was 110°. In order to further explore the effect of PFCB aryl ether structure on the properties of polycarbonate, a series of polycarbonates with different PFCB aryl ether group contents were synthesized from PFCB aryl ether monomer and bisphenol A monomer. By comparing their properties, the introduction of PFCB aryl ether structure into polycarbonate can reduce its dispersion and improve its thermal stability and hydrophobicity.
A novel hydrophobic polycarbonate containing perfluorocyclobutyl (PFCB) aryl ether was synthesized from commercially available p-methoxyphenol. The polymer exhibited excellent thermal stability and hydrophobicity without reducing the transparency of the material. The thermal decomposition temperature was 351℃ and the contact angle between the film and water was 110°. In order to further explore the effect of PFCB aryl ether structure on the properties of polycarbonate, a series of polycarbonates with different PFCB aryl ether group contents were synthesized from PFCB aryl ether monomer and bisphenol A monomer. By comparing their properties, the introduction of PFCB aryl ether structure into polycarbonate can reduce its dispersion and improve its thermal stability and hydrophobicity.
2019, 39(9): 2645-2649
doi: 10.6023/cjoc201812029
Abstract:
The cyclopropene compound contains an intra carbon-carbon double bond structure, which leads to distinctive active chemical reactivity due to the large ring tension. In this paper, the N-bromosuccinimide-promoted regioselective ring-opening of cyclopropene dicarboxylates to give functionalized α, β-unsaturated carboxylic acid ester compounds was studied. The reaction conditions are mild and the operation is simple.
The cyclopropene compound contains an intra carbon-carbon double bond structure, which leads to distinctive active chemical reactivity due to the large ring tension. In this paper, the N-bromosuccinimide-promoted regioselective ring-opening of cyclopropene dicarboxylates to give functionalized α, β-unsaturated carboxylic acid ester compounds was studied. The reaction conditions are mild and the operation is simple.
2019, 39(9): 2492-2498
doi: 10.6023/cjoc201903033
Abstract:
Recently, fluorescent labeling techniques have been greatly developed with the aid of highly optimized small-molecule fluorescent dyes, fluorescent proteins and advanced tagging techniques. Many reasonable strategies have been used to design fluorescent diarylethene, mainly focusing on the introduction of luminophores by conjugated junction and the modification of aryl cores in the diarylethene. Compared to thiophene, furan has superior properties such as solubility, biodegradable ability and rigidity fluorescence. Therefore, difurylethene is a better candidate for fluorescent labeling techniques. Herein, a new fluorescent photoswitch based on dicyano-vinyl modified difurylethenes was designed and prepared. This compound demonstrates typical reversible photochromism in solution and outstanding performance for the fluorescent detection of cyanide ions with excellent selectivity, sensitivity and high contrast. Furthermore, the mechanism of sensing toward cyanide ions was explained by 1H NMR titrations experiments. Owing to the strong fluorescence from a superior derivation with furan instead of thiophene, it is successfully applied as the fluorescent dyes and probe for detecting cyanide ions in vivo application.
Recently, fluorescent labeling techniques have been greatly developed with the aid of highly optimized small-molecule fluorescent dyes, fluorescent proteins and advanced tagging techniques. Many reasonable strategies have been used to design fluorescent diarylethene, mainly focusing on the introduction of luminophores by conjugated junction and the modification of aryl cores in the diarylethene. Compared to thiophene, furan has superior properties such as solubility, biodegradable ability and rigidity fluorescence. Therefore, difurylethene is a better candidate for fluorescent labeling techniques. Herein, a new fluorescent photoswitch based on dicyano-vinyl modified difurylethenes was designed and prepared. This compound demonstrates typical reversible photochromism in solution and outstanding performance for the fluorescent detection of cyanide ions with excellent selectivity, sensitivity and high contrast. Furthermore, the mechanism of sensing toward cyanide ions was explained by 1H NMR titrations experiments. Owing to the strong fluorescence from a superior derivation with furan instead of thiophene, it is successfully applied as the fluorescent dyes and probe for detecting cyanide ions in vivo application.
2019, 39(9): 2507-2514
doi: 10.6023/cjoc201902033
Abstract:
A series of 4-substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) semicarbazides were synthesized via molecular hybridization strategy. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by methyl thiazolyl tetrazolium (MTT) assay. 1-(2-Methyl-6-(pyridin-3-yl)nicotinoyl)-4-(2, 4, 6-trichlorophenyl)semicarbazide (4n) showed significant anticancer activity in these cancer cell lines with a range of IC50 values from 8.89 μmol/L to 11.45 μmol/L. Further biology studies showed that 4n treatment obviously increased the level of cleaved PARP and induced the apoptosis in QGY-7703 cells.
A series of 4-substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) semicarbazides were synthesized via molecular hybridization strategy. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by methyl thiazolyl tetrazolium (MTT) assay. 1-(2-Methyl-6-(pyridin-3-yl)nicotinoyl)-4-(2, 4, 6-trichlorophenyl)semicarbazide (4n) showed significant anticancer activity in these cancer cell lines with a range of IC50 values from 8.89 μmol/L to 11.45 μmol/L. Further biology studies showed that 4n treatment obviously increased the level of cleaved PARP and induced the apoptosis in QGY-7703 cells.
2019, 39(9): 2515-2524
doi: 10.6023/cjoc201901042
Abstract:
The rearrangement activity of benzyl aryl ether catalyzed by polyphosphoric acid (PPA) was systematically investigated. Optimal structural tuning of substitutions of electron withdrawing group (EWG) and electron donating group (EDG) at phenolic moiety or benzyl moiety benefits the rearrangement and the regio-selectivity of the rearrangement obeyed the substitution directing rule at the aromatic ring. This readily available rearrangement method is of practical interest for the benzylation of diverse aromatic phenols.
The rearrangement activity of benzyl aryl ether catalyzed by polyphosphoric acid (PPA) was systematically investigated. Optimal structural tuning of substitutions of electron withdrawing group (EWG) and electron donating group (EDG) at phenolic moiety or benzyl moiety benefits the rearrangement and the regio-selectivity of the rearrangement obeyed the substitution directing rule at the aromatic ring. This readily available rearrangement method is of practical interest for the benzylation of diverse aromatic phenols.
2019, 39(9): 2541-2548
doi: 10.6023/cjoc201903022
Abstract:
In order to find more effective antitumor drugs, a series of novel 2, 4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1-methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitu-mor activity against PC-3 with IC50 value of 1.76 μmol·L-1, and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.
In order to find more effective antitumor drugs, a series of novel 2, 4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1-methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitu-mor activity against PC-3 with IC50 value of 1.76 μmol·L-1, and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.
2019, 39(9): 2560-2566
doi: 10.6023/cjoc201901023
Abstract:
One-pot three-component reactions catalyzed by 1, 4-diazabicyclo[2.2.2]octane (DABCO) for the synthesis of bicyclic ortho-aminocarbonitrile derivatives (21 examples, 68%~96%) have been developed. The reactions proceeded smoothly at room temperature and generated the corresponding products in short reaction time with high to excellent yields. Importantly, the desired products could be easily collected through simple filtration and washing with ethanol.
One-pot three-component reactions catalyzed by 1, 4-diazabicyclo[2.2.2]octane (DABCO) for the synthesis of bicyclic ortho-aminocarbonitrile derivatives (21 examples, 68%~96%) have been developed. The reactions proceeded smoothly at room temperature and generated the corresponding products in short reaction time with high to excellent yields. Importantly, the desired products could be easily collected through simple filtration and washing with ethanol.
2019, 39(9): 2581-2588
doi: 10.6023/cjoc201903004
Abstract:
A series of amide derivatives containing aromatic sulfide and sulfone groups synthesized in our previous work displayed excellent nematocidal activity at 200 μg/mL. In order to explore the effect of structural modification of the amide bridge on biological activity in a more delicate way, two series of novel target compounds were designed and synthesized by adopting amide group flipping and introducing N-sulfonyl substituted amide bonds. The bioassays indicated that the structural modification of the amide bridge had important effects on their nematocidal and fungicidal activities, which the introduction of the N-sulfonyl substituent on the amide group was favorable to improving the nematocidal activity in comparison with compounds Ⅰ. The molecular docking revealed that directly attaching the carbonyl or sulfonyl groups in the amide bridge to the aromatic rings was advantageous to the nematocidal activity.
A series of amide derivatives containing aromatic sulfide and sulfone groups synthesized in our previous work displayed excellent nematocidal activity at 200 μg/mL. In order to explore the effect of structural modification of the amide bridge on biological activity in a more delicate way, two series of novel target compounds were designed and synthesized by adopting amide group flipping and introducing N-sulfonyl substituted amide bonds. The bioassays indicated that the structural modification of the amide bridge had important effects on their nematocidal and fungicidal activities, which the introduction of the N-sulfonyl substituent on the amide group was favorable to improving the nematocidal activity in comparison with compounds Ⅰ. The molecular docking revealed that directly attaching the carbonyl or sulfonyl groups in the amide bridge to the aromatic rings was advantageous to the nematocidal activity.
2019, 39(9): 2632-2638
doi: 10.6023/cjoc201901037
Abstract:
Alkaline protease-catalyzed synthesis of quinazolinone derivatives was developed between β-keotester and o-aminobenzamide. Because ethanol is one kind of eco-friendly solvents, this method can reduce the impact of solvents on the environment. Alkaline protease as a biocatalyst has many advantages, e.g. high catalytic activity, environmentally friendly, wide variety of sources and simple operation. In addition, a variety of quinazolinone derivatives was obtained with good to excellent yields just using 2000 U alkaline protease as catalyst.
Alkaline protease-catalyzed synthesis of quinazolinone derivatives was developed between β-keotester and o-aminobenzamide. Because ethanol is one kind of eco-friendly solvents, this method can reduce the impact of solvents on the environment. Alkaline protease as a biocatalyst has many advantages, e.g. high catalytic activity, environmentally friendly, wide variety of sources and simple operation. In addition, a variety of quinazolinone derivatives was obtained with good to excellent yields just using 2000 U alkaline protease as catalyst.
2019, 39(9): 2650-2654
doi: 10.6023/cjoc201906001
Abstract:
A new method for the synthesis of 8-hydroxyisocoumarin is reported. 8-Hydroxyisocoumarin was synthesized from Meldrum's acid by Friedel-Crafts acylation, carbonyl protection, ester reduction and deprotection. The key intermediate 3-ethynyl-2-(hydroxymethyl)cyclohex-2-en-1-one was synthesized by acidic cycloaddition, aromatization of cyclohexanone ring and 2, 3-dicyano-5, 6-dichlorobenzoquinone (DDQ) oxidation. The structures were characterized by 1H NMR, 13C NMR, IR, and HRMS.
A new method for the synthesis of 8-hydroxyisocoumarin is reported. 8-Hydroxyisocoumarin was synthesized from Meldrum's acid by Friedel-Crafts acylation, carbonyl protection, ester reduction and deprotection. The key intermediate 3-ethynyl-2-(hydroxymethyl)cyclohex-2-en-1-one was synthesized by acidic cycloaddition, aromatization of cyclohexanone ring and 2, 3-dicyano-5, 6-dichlorobenzoquinone (DDQ) oxidation. The structures were characterized by 1H NMR, 13C NMR, IR, and HRMS.
2019, 39(9): 2655-2662
doi: 10.6023/cjoc201903056
Abstract:
A series of 3-arylisoxazoline-pyrazole-5-carboxamide derivatives derived from ethyl 5, 5-dimethoxy-2, 4-dioxopentanoate were designed, synthesized, and characterized by 1H NMR, 13C NMR and HRMS. The preliminary bioassay indicated that most title compounds exhibited positive potency against Mythimna separate (Walker) at 500 mg/L. At the concentration of 100 mg/L, three compounds were still moderately active against Mythimna separate (Walker) (lethal rate≈60%). At 500 mg/L, four compounds were also active against Aphis craccivora. The results indicated that the potential of these 3-arylisoxazoline-pyrazole-5-carboxamide derivatives can be utilized in insecticide research with further optimization.
A series of 3-arylisoxazoline-pyrazole-5-carboxamide derivatives derived from ethyl 5, 5-dimethoxy-2, 4-dioxopentanoate were designed, synthesized, and characterized by 1H NMR, 13C NMR and HRMS. The preliminary bioassay indicated that most title compounds exhibited positive potency against Mythimna separate (Walker) at 500 mg/L. At the concentration of 100 mg/L, three compounds were still moderately active against Mythimna separate (Walker) (lethal rate≈60%). At 500 mg/L, four compounds were also active against Aphis craccivora. The results indicated that the potential of these 3-arylisoxazoline-pyrazole-5-carboxamide derivatives can be utilized in insecticide research with further optimization.
2019, 39(9): 2663-2670
doi: 10.6023/cjoc201901041
Abstract:
Three kinds of C(3)-1, 2, 4-triazolyl-1, 5-benzothiazepines, 2, 3-dihydro/2, 5-dihydro/2, 3, 4, 5-tetrahydro-3-(1, 2, 4-tria-zolyl)-4-aryl-1, 5-benzothiazepines, were designed and synthesized. The synthesis conditions of intermediates and target products were studied, and the structures of two by-products were determined. The antimicrobial activity test of the target products showed that 2, 3-dihydro/2, 5-dihydro-3-(1, 2, 4-triazolyl)-4-aryl-1, 5-benzothiazepines exhibited high inhibitory effects on C. neoformans and C. albicans. At concentration of 200 μg/disc, the inhibitory effects of four compounds on C. neoformans were stronger than that of fluconazol, and the inhibitory effects of three compounds on C. albicans were stronger than that of fluconazol. The preliminary study on the structure-activity relationship of antifungal revealed that 1, 2, 4-triazolyl and C=N double bond were the key function groups in the antifungal activity of 2, 3-dihydro-3-(1, 2, 4-triazolyl)-4-aryl-1, 5-benzothiazepines.
Three kinds of C(3)-1, 2, 4-triazolyl-1, 5-benzothiazepines, 2, 3-dihydro/2, 5-dihydro/2, 3, 4, 5-tetrahydro-3-(1, 2, 4-tria-zolyl)-4-aryl-1, 5-benzothiazepines, were designed and synthesized. The synthesis conditions of intermediates and target products were studied, and the structures of two by-products were determined. The antimicrobial activity test of the target products showed that 2, 3-dihydro/2, 5-dihydro-3-(1, 2, 4-triazolyl)-4-aryl-1, 5-benzothiazepines exhibited high inhibitory effects on C. neoformans and C. albicans. At concentration of 200 μg/disc, the inhibitory effects of four compounds on C. neoformans were stronger than that of fluconazol, and the inhibitory effects of three compounds on C. albicans were stronger than that of fluconazol. The preliminary study on the structure-activity relationship of antifungal revealed that 1, 2, 4-triazolyl and C=N double bond were the key function groups in the antifungal activity of 2, 3-dihydro-3-(1, 2, 4-triazolyl)-4-aryl-1, 5-benzothiazepines.
2019, 39(9): 2676-2680
doi: 10.6023/cjoc201902020
Abstract:
Puquitinib mesylate is a novel phosphatidylinositol 3-kinases (PI3K) inhibitor, which has been shown to be effective in the treatment of cancer. A convenient protocol for the synthesis of the compound at kilogram scale is described, using 2, 6-dichloropurine as starting material through amino-protection, SN2 reaction with high regioselectivity, Buchwald-Hartwig coupling reaction, amino-deprotection and salt-forming reaction. The process is easy to operate and provides an effective way at kilogram scale produce with 48% yield in total.
Puquitinib mesylate is a novel phosphatidylinositol 3-kinases (PI3K) inhibitor, which has been shown to be effective in the treatment of cancer. A convenient protocol for the synthesis of the compound at kilogram scale is described, using 2, 6-dichloropurine as starting material through amino-protection, SN2 reaction with high regioselectivity, Buchwald-Hartwig coupling reaction, amino-deprotection and salt-forming reaction. The process is easy to operate and provides an effective way at kilogram scale produce with 48% yield in total.
2019, 39(9): 2671-2675
doi: 10.6023/cjoc201903014
Abstract:
A concise synthesis of 3-dehydroxyphomonol has been accomplished in six steps from commercially available (R)-4-chloro-3-hydroxy-butyric acid ethyl ester or (S)-2-propyl-oxirane. The key steps involved Grignard reaction, Prins cyclization and palladium-catalyzed intramolecular alkoxycarbonylation to install the tetrahydropyran ring. The synthesis demonstrated an application of protecting-group-free strategy.
A concise synthesis of 3-dehydroxyphomonol has been accomplished in six steps from commercially available (R)-4-chloro-3-hydroxy-butyric acid ethyl ester or (S)-2-propyl-oxirane. The key steps involved Grignard reaction, Prins cyclization and palladium-catalyzed intramolecular alkoxycarbonylation to install the tetrahydropyran ring. The synthesis demonstrated an application of protecting-group-free strategy.
