Login In
2019 Volume 39 Issue 7
2019, 39(7): 1811-1830
doi: 10.6023/cjoc201902019
Abstract:
The C-H bond activation has become one of the hot fields of organic chemistry in recent years due to its atom economy and step simplicity. In the conventional C-H bond activations, an equivalent amount of oxidants is usually added to regenerate the catalyst and allow the catalytic cycle proceed smoothly. N-Phenoxyacetamide, as a novel reaction substrate containing an oxidizing directing group, can effectively avoid the use of an equivalent external oxidants. Thus, the C-H activation could be conducted under redox neutral conditions. In this paper, the latest research progress of N-phenoxyacetamides in the field of organic synthesis, especially C-H bond activations is reviewed, and the mechanism of the reaction is discussed.
The C-H bond activation has become one of the hot fields of organic chemistry in recent years due to its atom economy and step simplicity. In the conventional C-H bond activations, an equivalent amount of oxidants is usually added to regenerate the catalyst and allow the catalytic cycle proceed smoothly. N-Phenoxyacetamide, as a novel reaction substrate containing an oxidizing directing group, can effectively avoid the use of an equivalent external oxidants. Thus, the C-H activation could be conducted under redox neutral conditions. In this paper, the latest research progress of N-phenoxyacetamides in the field of organic synthesis, especially C-H bond activations is reviewed, and the mechanism of the reaction is discussed.
2019, 39(7): 1831-1836
doi: 10.6023/cjoc201903001
Abstract:
Arylmethyl azides (ArCH2N3) as one of the significant nitrogen sources with stable properties, simple synthesis, have been widely used in a wide range of organic synthesis reactions. The recent progress (2014~2018) on reactions of arylmethyl azides with alkenes is summarized. In addition, the organic reactions of arylmethyl azides with types of alkenes are described respectively, with their scope of substrates and reaction mechanism. It is hoped that this review can be referred to the future application in organic synthesis of arylmethyl azides with alkenes.
Arylmethyl azides (ArCH2N3) as one of the significant nitrogen sources with stable properties, simple synthesis, have been widely used in a wide range of organic synthesis reactions. The recent progress (2014~2018) on reactions of arylmethyl azides with alkenes is summarized. In addition, the organic reactions of arylmethyl azides with types of alkenes are described respectively, with their scope of substrates and reaction mechanism. It is hoped that this review can be referred to the future application in organic synthesis of arylmethyl azides with alkenes.
2019, 39(7): 1837-1845
doi: 10.6023/cjoc201902006
Abstract:
Anodic oxidation of aryl iodine compouds is a green and efficient method for the synthesis of hypervalent iodine reagents. This method replaces chemical reagents with electric current, avoiding the use of expensive and handle difficult oxidants such as m-CPBA, H2O2, oxone, selectfluor etc. Electrochemically generated hypervalent iodine reagents can not only promote fluorination, oxidative cyclization, but also be successfully applied in the total synthesis of natural products. In addition, recyclable aryl iodine mediator can be used to indirect anodic fluorination and easily separated from products. The organic electrochemical synthesis of hypervalent iodine reagents and their applications in various chemical transformations are reviewed.
Anodic oxidation of aryl iodine compouds is a green and efficient method for the synthesis of hypervalent iodine reagents. This method replaces chemical reagents with electric current, avoiding the use of expensive and handle difficult oxidants such as m-CPBA, H2O2, oxone, selectfluor etc. Electrochemically generated hypervalent iodine reagents can not only promote fluorination, oxidative cyclization, but also be successfully applied in the total synthesis of natural products. In addition, recyclable aryl iodine mediator can be used to indirect anodic fluorination and easily separated from products. The organic electrochemical synthesis of hypervalent iodine reagents and their applications in various chemical transformations are reviewed.
2019, 39(7): 1846-1857
doi: 10.6023/cjoc201901033
Abstract:
The multifunctional fluorescent probes can detect a plurality of anions and cations or other small molecules. These probes can greatly improve the detection efficiency and reduce the analysis cost with respect to the mono-analyte fluorescent probes. Thus, they have attracted much attention in recent years. According to their molecular structural characteristics, the reported multifunctional fluorescent probes are divided into three types as organic small molecules, polymers and metal-organic complexes. The new progress on their molecular design, synthesis and detecting application is reviewed on the viewpoint of sensing objects and performances. The developing potential of multifunctional fluorescent probes is envisioned also, and the probes capable of simultaneously identifying multiple analytes in the same system should be highlighted in the future
The multifunctional fluorescent probes can detect a plurality of anions and cations or other small molecules. These probes can greatly improve the detection efficiency and reduce the analysis cost with respect to the mono-analyte fluorescent probes. Thus, they have attracted much attention in recent years. According to their molecular structural characteristics, the reported multifunctional fluorescent probes are divided into three types as organic small molecules, polymers and metal-organic complexes. The new progress on their molecular design, synthesis and detecting application is reviewed on the viewpoint of sensing objects and performances. The developing potential of multifunctional fluorescent probes is envisioned also, and the probes capable of simultaneously identifying multiple analytes in the same system should be highlighted in the future
2019, 39(7): 1858-1866
doi: 10.6023/cjoc201901001
Abstract:
Compared with traditional material removal-cutting method, 3D printing is a "bottom-up" material accumulation manufacturing technology. This novel technology is not only simple to operate, but also has a lower manufacturing cost and can be quickly generated. What's more, 3D printing technology can fabricate the be-spoke objects with intricate internal structures. Therefore, 3D printing has been a representative technology of the third industrial revolution. In recent years, chemists have combined 3D printing technology with organic synthesis and made many good achievements in the development of new multichannel heterogeneous catalysts and reaction devices, which has made this technology more and more widely used in the field of organic synthesis. In this review, the progress of the organic synthesis based on 3D printing technology from 2012 to 2018 are summarized, such as 3D-printed heterogeneous catalysts, 3D-printed devices and 3D-printed continuous flow microreactors. Furthermore, the development trends of this field in the future are also prospected.
Compared with traditional material removal-cutting method, 3D printing is a "bottom-up" material accumulation manufacturing technology. This novel technology is not only simple to operate, but also has a lower manufacturing cost and can be quickly generated. What's more, 3D printing technology can fabricate the be-spoke objects with intricate internal structures. Therefore, 3D printing has been a representative technology of the third industrial revolution. In recent years, chemists have combined 3D printing technology with organic synthesis and made many good achievements in the development of new multichannel heterogeneous catalysts and reaction devices, which has made this technology more and more widely used in the field of organic synthesis. In this review, the progress of the organic synthesis based on 3D printing technology from 2012 to 2018 are summarized, such as 3D-printed heterogeneous catalysts, 3D-printed devices and 3D-printed continuous flow microreactors. Furthermore, the development trends of this field in the future are also prospected.
2019, 39(7): 1867-1874
doi: 10.6023/cjoc201901029
Abstract:
Phenylalanine derivatives are widely found in a broad range of pharmaceutical molecules and exhibit significant biological activity. Direct C-H bond functionalization of phenylalanine derivatives to offer an efficient approach to construct C-I, C(sp2)-C(sp2), C(sp2)-C(sp), C(sp2)-C(sp3), C-N, C-B and C-O bonds is described. The transformation involves ortho-C-H bond iodination and the following intramolecular amination, ortho-alkylation, ortho-arylation, ortho-alkenylation, ortho-alkynylation, ortho-acylation, ortho-acetoxylation, ortho-amination, ortho-boronation, meta-arylation and meta-alky-lation.
Phenylalanine derivatives are widely found in a broad range of pharmaceutical molecules and exhibit significant biological activity. Direct C-H bond functionalization of phenylalanine derivatives to offer an efficient approach to construct C-I, C(sp2)-C(sp2), C(sp2)-C(sp), C(sp2)-C(sp3), C-N, C-B and C-O bonds is described. The transformation involves ortho-C-H bond iodination and the following intramolecular amination, ortho-alkylation, ortho-arylation, ortho-alkenylation, ortho-alkynylation, ortho-acylation, ortho-acetoxylation, ortho-amination, ortho-boronation, meta-arylation and meta-alky-lation.
2019, 39(7): 1875-1890
doi: 10.6023/cjoc201811002
Abstract:
Flavonoid glycoside is commonly found in natural plants, possesses diverse bioactivities and potential medicinal values, and its synthesis methods are worthy to be studied. The synthesis of flavonoid glycosides covering the literatures from 2014 to 2018 is reviewed. The flavonoid glycoside synthesis includes two major methods of chemosynthesis and biosynthesis. Chemosynthesis includes total synthesis and semi-synthesis. The total synthesis has two classical methods of the Baker- Venkataraman (BK-VK) reaction and the Algar-Flynn-Oyamada (AFO) reaction. The semi-synthesis is usually starting from natural flavonoid, such as rutin, quercetin, kaempferol, naringenin and so on. Moreover, the chemosynthesis of flavonoid O-glucoside has three prime methods, Koening-Knorr method, phase transfer catalysis method, and glycosyl trichloroacetimidate method. As for the chemosynthesis of flavonoid C-glycoside, its glycosidic linkage is mainly completed via the O→C rearrangement reaction. Currently, the glycosyltransferase and glycosynthase are usually employed in the enzyme-catalyzed biosynthesis of flavonoid glycosides.
Flavonoid glycoside is commonly found in natural plants, possesses diverse bioactivities and potential medicinal values, and its synthesis methods are worthy to be studied. The synthesis of flavonoid glycosides covering the literatures from 2014 to 2018 is reviewed. The flavonoid glycoside synthesis includes two major methods of chemosynthesis and biosynthesis. Chemosynthesis includes total synthesis and semi-synthesis. The total synthesis has two classical methods of the Baker- Venkataraman (BK-VK) reaction and the Algar-Flynn-Oyamada (AFO) reaction. The semi-synthesis is usually starting from natural flavonoid, such as rutin, quercetin, kaempferol, naringenin and so on. Moreover, the chemosynthesis of flavonoid O-glucoside has three prime methods, Koening-Knorr method, phase transfer catalysis method, and glycosyl trichloroacetimidate method. As for the chemosynthesis of flavonoid C-glycoside, its glycosidic linkage is mainly completed via the O→C rearrangement reaction. Currently, the glycosyltransferase and glycosynthase are usually employed in the enzyme-catalyzed biosynthesis of flavonoid glycosides.
2019, 39(7): 1891-1912
doi: 10.6023/cjoc201812016
Abstract:
Tumor is one of the diseases with the highest mortality rate in the world. In view of the high risk and high mortality of tumor, researchers around the world are committed to develop more accurate and rapid diagnostic strategies and more effective treatments to fight tumor. Gradually, integrated optical diagnosis and treatment technologies for tumors have emerged. Fluoroboron fluorescein (BODIPY) has been widely used in tumor phototherapy because of its excellent optical properties. In this paper, BODIPY and its derivatives are introduced in detail as photosensitizers, photothermal transformants, and contrast agents in the diagnosis and treatment of tumors (photodynamic therapy, photothermal therapy, photoacoustic imaging) and integration of diagnosis and treatment. The effects of different BODIPY structures and their derivatives in tumor diagnosis and treatment were evaluated systematically. This is of great significance for the rational design of near-infrared BODIPY materials with high singlet oxygen quantum yield, high photothermal conversion, and good light stability and solubility.
Tumor is one of the diseases with the highest mortality rate in the world. In view of the high risk and high mortality of tumor, researchers around the world are committed to develop more accurate and rapid diagnostic strategies and more effective treatments to fight tumor. Gradually, integrated optical diagnosis and treatment technologies for tumors have emerged. Fluoroboron fluorescein (BODIPY) has been widely used in tumor phototherapy because of its excellent optical properties. In this paper, BODIPY and its derivatives are introduced in detail as photosensitizers, photothermal transformants, and contrast agents in the diagnosis and treatment of tumors (photodynamic therapy, photothermal therapy, photoacoustic imaging) and integration of diagnosis and treatment. The effects of different BODIPY structures and their derivatives in tumor diagnosis and treatment were evaluated systematically. This is of great significance for the rational design of near-infrared BODIPY materials with high singlet oxygen quantum yield, high photothermal conversion, and good light stability and solubility.
2019, 39(7): 1913-1922
doi: 10.6023/cjoc201810037
Abstract:
Since the first tetrahydroisoquinoline alkaloid (THIQ), naphthyridinomycin, was found by Canadian scientist Kluepfel in 1974, nearly hundred members of this family have been reported. Such THIQ has attracted the research interest of many chemists and biologists due to its excellent biological activity and complex chemical structure. Especially, as an outstanding member of THIQ family, Ecteinascidin 743 (ET-743) has been commercialized in the European Union for the treatment of soft tissue tumors and ovarian cancer. Due to the extremely low content of natural products of bistetrahydroisoquinoline including ET-743 and the complexity of its chemical structure, the modification of its chemical structure has attracted more and more attention. Based on this, the recent advance in the synthesis of bistetrahydroisoquinoline analogues is reviewed.
Since the first tetrahydroisoquinoline alkaloid (THIQ), naphthyridinomycin, was found by Canadian scientist Kluepfel in 1974, nearly hundred members of this family have been reported. Such THIQ has attracted the research interest of many chemists and biologists due to its excellent biological activity and complex chemical structure. Especially, as an outstanding member of THIQ family, Ecteinascidin 743 (ET-743) has been commercialized in the European Union for the treatment of soft tissue tumors and ovarian cancer. Due to the extremely low content of natural products of bistetrahydroisoquinoline including ET-743 and the complexity of its chemical structure, the modification of its chemical structure has attracted more and more attention. Based on this, the recent advance in the synthesis of bistetrahydroisoquinoline analogues is reviewed.
2019, 39(7): 1923-1929
doi: 10.6023/cjoc201901014
Abstract:
Pyrazoles, a class of five-membered nitrogen-containing heterocyclic compounds, showed antibacterial, anticancer and antioxidative activity, and so on. They also served as important intermediates in organic synthesis. To develop the general and straightforward methods to their synthesis is of great significance. In this paper, a series of tetra-substituted pyrazoles were synthesized from aldehydes, hydrazines and fumarate esters by three-component[3+2] cycloaddition reaction in the presence of chloroamine-T with 60%~87% yields. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis.
Pyrazoles, a class of five-membered nitrogen-containing heterocyclic compounds, showed antibacterial, anticancer and antioxidative activity, and so on. They also served as important intermediates in organic synthesis. To develop the general and straightforward methods to their synthesis is of great significance. In this paper, a series of tetra-substituted pyrazoles were synthesized from aldehydes, hydrazines and fumarate esters by three-component[3+2] cycloaddition reaction in the presence of chloroamine-T with 60%~87% yields. Their structures were confirmed by 1H NMR, 13C NMR, IR and HRMS analysis.
2019, 39(7): 1939-1944
doi: 10.6023/cjoc201811016
Abstract:
In this paper, the intermediate of 4-amino-5-methyl-1, 2, 4-triazole-3-thione (M1) was synthesized with thioformyl hydrazide and acetic acid, and 4-amino-5-aryl-1, 2, 4-triazole-3-thione (M2) was got by esterification, hydrazide, salt formation and cyclization with substituted benzoic acid. Four compounds of 1, 2, 4-triazole Schiff bases containing the pyrimidine ring M1-1, M2-1, M2-2 and M2-3 were obtained with 4, 6-dichloro-5-pyrimidinecarboxaldehyde and M1/M2 according to the addition-elimination reaction. The structures of the compounds were characterized by elemental analysis, IR and 1H NMR spectra. The bioactivities and antibacterial mechanism of the title compounds were also studied by mycelial growth rate method and molecular docking. The results showed that the compounds had certain inhibitory effects on different fungi. Based on the values of EC50, compounds M1-1, M2-2 and M2-3 have better antifungal effects against the wheat gibberella than that of the standard drug (fluconazole), which is corresponding to the result of molecular docking.
In this paper, the intermediate of 4-amino-5-methyl-1, 2, 4-triazole-3-thione (M1) was synthesized with thioformyl hydrazide and acetic acid, and 4-amino-5-aryl-1, 2, 4-triazole-3-thione (M2) was got by esterification, hydrazide, salt formation and cyclization with substituted benzoic acid. Four compounds of 1, 2, 4-triazole Schiff bases containing the pyrimidine ring M1-1, M2-1, M2-2 and M2-3 were obtained with 4, 6-dichloro-5-pyrimidinecarboxaldehyde and M1/M2 according to the addition-elimination reaction. The structures of the compounds were characterized by elemental analysis, IR and 1H NMR spectra. The bioactivities and antibacterial mechanism of the title compounds were also studied by mycelial growth rate method and molecular docking. The results showed that the compounds had certain inhibitory effects on different fungi. Based on the values of EC50, compounds M1-1, M2-2 and M2-3 have better antifungal effects against the wheat gibberella than that of the standard drug (fluconazole), which is corresponding to the result of molecular docking.
2019, 39(7): 1945-1952
doi: 10.6023/cjoc201901050
Abstract:
Under the catalysis of solid acidic ion exchange resin Amberlyst-15, using ethanol as solvent, aromatic aldehyde, β-ketoester, and 3-amino-1, 2, 4-triazole or 2-aminobenzo as starting materials, a series of triazolo[1, 5-a]pyrimidine derivatives 5a~5m and dihydrobenzo[4,5]imidazo[1, 2-a]pyrimidines 6a~6g were synthesized by three-component one-pot reaction of imidazole derivatives. The method is simple and efficient, and has short reaction time, simple post-treatment and wide application range of the substrate. The catalyst can be recycled for 4 times without the significant decrease of catalytic activity. It conforms to the basic standard of green chemistry.
Under the catalysis of solid acidic ion exchange resin Amberlyst-15, using ethanol as solvent, aromatic aldehyde, β-ketoester, and 3-amino-1, 2, 4-triazole or 2-aminobenzo as starting materials, a series of triazolo[1, 5-a]pyrimidine derivatives 5a~5m and dihydrobenzo[4,5]imidazo[1, 2-a]pyrimidines 6a~6g were synthesized by three-component one-pot reaction of imidazole derivatives. The method is simple and efficient, and has short reaction time, simple post-treatment and wide application range of the substrate. The catalyst can be recycled for 4 times without the significant decrease of catalytic activity. It conforms to the basic standard of green chemistry.
2019, 39(7): 1962-1969
doi: 10.6023/cjoc201811004
Abstract:
Study on the synthesis and bioactivity of benzophenanthridine alkaloids or its analogues had been the interests of many reserach groups who dedicated to organic synthsis or medicinal chemistry, due to their broad spectrum of biological activities such as antitumor, antiviral, antiinflammatory, antibacterial and so on. In this paper, twenty three novel analogue of benzophenanthridines were synthesized starting from isochroman-3-one and aromatic amines in 3~4 steps via the cyclization reaction of aryl-enamine ester as the key transformation. The structures of the targeted compounds were characterized and comfirmed by 1H NMR, 13C NMR and HRMS. In vitro cytotoxic activity against a panel of human tumor cell lines (MGC-803, HepG2, NCI-H460, SKOV3, T-24) and nomal cell HL-7702 was also evaluated via methyl thiazolyl tetrazolium (MTT) assay. The result indicated that only a very few of the targeted compounds exhibted moderate cytotoxic activity against the tested cell lines. Among them 2, 3-dimethoxy-isochrysen[4, 3-c]quinoline (4j) and 2-chloro-isochromone[4, 3-c]quinoline (5f) displayed moderate antiproliferative activity against human tumor cell lines on T-24 and NCI-H460 with IC50 values of 15.8 and 16.7 μmol/L, respectively.
Study on the synthesis and bioactivity of benzophenanthridine alkaloids or its analogues had been the interests of many reserach groups who dedicated to organic synthsis or medicinal chemistry, due to their broad spectrum of biological activities such as antitumor, antiviral, antiinflammatory, antibacterial and so on. In this paper, twenty three novel analogue of benzophenanthridines were synthesized starting from isochroman-3-one and aromatic amines in 3~4 steps via the cyclization reaction of aryl-enamine ester as the key transformation. The structures of the targeted compounds were characterized and comfirmed by 1H NMR, 13C NMR and HRMS. In vitro cytotoxic activity against a panel of human tumor cell lines (MGC-803, HepG2, NCI-H460, SKOV3, T-24) and nomal cell HL-7702 was also evaluated via methyl thiazolyl tetrazolium (MTT) assay. The result indicated that only a very few of the targeted compounds exhibted moderate cytotoxic activity against the tested cell lines. Among them 2, 3-dimethoxy-isochrysen[4, 3-c]quinoline (4j) and 2-chloro-isochromone[4, 3-c]quinoline (5f) displayed moderate antiproliferative activity against human tumor cell lines on T-24 and NCI-H460 with IC50 values of 15.8 and 16.7 μmol/L, respectively.
2019, 39(7): 1970-1975
doi: 10.6023/cjoc201901030
Abstract:
The first[3+3] cycloaddition reaction of in situ-generated aza-oxyallyl cations with oximes was developed. This approach provides a simple and efficient method for the synthesis of 2-N-unsubstituted 1, 2, 4-oxadiazin-5-one derivatives with many merits, such as easy available regents, mild reaction conditions and high yield.
The first[3+3] cycloaddition reaction of in situ-generated aza-oxyallyl cations with oximes was developed. This approach provides a simple and efficient method for the synthesis of 2-N-unsubstituted 1, 2, 4-oxadiazin-5-one derivatives with many merits, such as easy available regents, mild reaction conditions and high yield.
2019, 39(7): 1976-1982
doi: 10.6023/cjoc201812020
Abstract:
8-Prenylflavonoids are a class natural products with significant biological activities. The total synthesis of three prenylflavonoid natural products, 8-prenylquercetin-3-methylether (1), 8-prenylquerccetin-3, 7, 3', 4'-tetramethyl ether (2) and Artochamin C (3), was achieved through methoxymethyl protection, aldol condensation, iodine catalytic cyclization, dimethyl sulfoxide (DMSO) oxidation, O-prenylation, microwave promoted Claisen rearrangement, deprotection, O-methylation and prenyl group side chain cyclization, staring from commercially available 2, 4, 6-trihydroxyacetophenone and 3, 4-dihydroxy benzaldehyde. The key step of microwave promoted Claisen rearrangement formed 8-C-prenylflavonoids from 5-O- prenylflavonoids was investigated. All the synthesized compounds were confirmed by 1H NMR、13C NMR and MS techniques.
8-Prenylflavonoids are a class natural products with significant biological activities. The total synthesis of three prenylflavonoid natural products, 8-prenylquercetin-3-methylether (1), 8-prenylquerccetin-3, 7, 3', 4'-tetramethyl ether (2) and Artochamin C (3), was achieved through methoxymethyl protection, aldol condensation, iodine catalytic cyclization, dimethyl sulfoxide (DMSO) oxidation, O-prenylation, microwave promoted Claisen rearrangement, deprotection, O-methylation and prenyl group side chain cyclization, staring from commercially available 2, 4, 6-trihydroxyacetophenone and 3, 4-dihydroxy benzaldehyde. The key step of microwave promoted Claisen rearrangement formed 8-C-prenylflavonoids from 5-O- prenylflavonoids was investigated. All the synthesized compounds were confirmed by 1H NMR、13C NMR and MS techniques.
2019, 39(7): 1990-1995
doi: 10.6023/cjoc201811003
Abstract:
One hybrid host molecule of dibenzo-24-crown-8 bridged pillar[5]arene dimer (1) was designed and synthesized. The combination of host 1 and ditopic guest 2 containing two 5-(1H-1, 2, 3-triazol-1-yl)pentanenitrile (TAPN) binding sites could afford linear AA/BB-type supramolecular polymers based on TAPN•pillar[5]arene recognition motif. Further introduction of ditopic guest 3 containing two secondary ammonium parts yields cross-linked supramolecular polymers through the host-guest inclusion between dibenzo-24-crown-8 and secondary ammonium salt. The supramolecular polymers were characterized by various techniques such as 1H NMR, viscosity, DOSY and SEM, indicating that the formation of these supramolecular polymer was concentration-dependent. The critical polymerization concentration (CPC) of the formation of linear supramolecular polymers in chloroform/acetone (V:V=4:1) solutions is 28 mmol/L. This work provides a new strategy for the fabrication of novel supramolecular aggregates based on orthogonal host-guest interactions of hybrid macrocycles.
One hybrid host molecule of dibenzo-24-crown-8 bridged pillar[5]arene dimer (1) was designed and synthesized. The combination of host 1 and ditopic guest 2 containing two 5-(1H-1, 2, 3-triazol-1-yl)pentanenitrile (TAPN) binding sites could afford linear AA/BB-type supramolecular polymers based on TAPN•pillar[5]arene recognition motif. Further introduction of ditopic guest 3 containing two secondary ammonium parts yields cross-linked supramolecular polymers through the host-guest inclusion between dibenzo-24-crown-8 and secondary ammonium salt. The supramolecular polymers were characterized by various techniques such as 1H NMR, viscosity, DOSY and SEM, indicating that the formation of these supramolecular polymer was concentration-dependent. The critical polymerization concentration (CPC) of the formation of linear supramolecular polymers in chloroform/acetone (V:V=4:1) solutions is 28 mmol/L. This work provides a new strategy for the fabrication of novel supramolecular aggregates based on orthogonal host-guest interactions of hybrid macrocycles.
2019, 39(7): 1996-2000
doi: 10.6023/cjoc201901019
Abstract:
Sodium hypochlorite has been used as a green oxidant in oxidation of alcohols. However, the oxidation of a-hydroxyl ester via sodium hypochloriteis difficult under the same conditions. Herein, an efficient method is developed for the oxidation of a-hydroxyl ester with sodium hypochlorite in the presence of hydrogenbromide. In this case, a reaction mechanism was proposed with the formation of free radicals as reactive intermediates, which was different from the mechanism of traditional Stevens oxidation. The method is also applied to the oxidation of common secondary alcohol and has good selectivity for multi-hydroxyl compounds.
Sodium hypochlorite has been used as a green oxidant in oxidation of alcohols. However, the oxidation of a-hydroxyl ester via sodium hypochloriteis difficult under the same conditions. Herein, an efficient method is developed for the oxidation of a-hydroxyl ester with sodium hypochlorite in the presence of hydrogenbromide. In this case, a reaction mechanism was proposed with the formation of free radicals as reactive intermediates, which was different from the mechanism of traditional Stevens oxidation. The method is also applied to the oxidation of common secondary alcohol and has good selectivity for multi-hydroxyl compounds.
2019, 39(7): 2009-2017
doi: 10.6023/cjoc201902015
Abstract:
Three azobenzenes 4~6 conjugated with 4, 4'-dimethoxy-triphenylamine redox center have been synthesized by palladium-catalyzed Sonogashira coupling reactions in moderate yield after column chromatographic purification. They are all stable when exposed in air and moisture in both the solid and solution state. The 1H NMR spectra of 4~6 showned that the azobenzene groups are in the trans configuration. The UV/Vis spectra of the target molecule were studied. The UV/Vis absorption bands of 4~6 are less clearly separated, which is similar to those for aminoazobenzen or pseudostilbene. The absorption bands at the π→π* band of 4 and 6 are redshifted, due to the strong electronic interaction between the azobenzene unit and the para-triphenylamine unit, which results in the formation of a longer conjugation system than the corresponding meta isomers. Electrochemical and spectroelectrochemical studies indicate excellent redox reversibility of these compounds. Significant spectra change upon the process of redox makes these compounds have potential applications of electrochemical switching. Among the derivatives, compound 4 exhibits the highest cis form (45%) in the photostationary state (PSS) upon light irradiation at 435 nm. The photoisomerization studies indicate that the photochemistry properties is strongly influenced by the substituted position of the triphenylamine moiety. Photoisomerization studies showed that these compounds have fast photoisomerization rate due to the higher photoisomerization quantum yield, which is an order of magnitude larger than that of ferrocenyl (ethynyl) azobenzenes. Both compounds 4 and 6 exhibit excellent fatigue resistance and reversibility under several repeated reversible isomerization cycles. The cis-to-trans photoisomerization of 4 can be not only achieved by irradiation at UV lignt, but also realized by a more efficient way of change the state of redox center. Our study will provide a good basis for research in design new type of multiple-response molecular switches.
Three azobenzenes 4~6 conjugated with 4, 4'-dimethoxy-triphenylamine redox center have been synthesized by palladium-catalyzed Sonogashira coupling reactions in moderate yield after column chromatographic purification. They are all stable when exposed in air and moisture in both the solid and solution state. The 1H NMR spectra of 4~6 showned that the azobenzene groups are in the trans configuration. The UV/Vis spectra of the target molecule were studied. The UV/Vis absorption bands of 4~6 are less clearly separated, which is similar to those for aminoazobenzen or pseudostilbene. The absorption bands at the π→π* band of 4 and 6 are redshifted, due to the strong electronic interaction between the azobenzene unit and the para-triphenylamine unit, which results in the formation of a longer conjugation system than the corresponding meta isomers. Electrochemical and spectroelectrochemical studies indicate excellent redox reversibility of these compounds. Significant spectra change upon the process of redox makes these compounds have potential applications of electrochemical switching. Among the derivatives, compound 4 exhibits the highest cis form (45%) in the photostationary state (PSS) upon light irradiation at 435 nm. The photoisomerization studies indicate that the photochemistry properties is strongly influenced by the substituted position of the triphenylamine moiety. Photoisomerization studies showed that these compounds have fast photoisomerization rate due to the higher photoisomerization quantum yield, which is an order of magnitude larger than that of ferrocenyl (ethynyl) azobenzenes. Both compounds 4 and 6 exhibit excellent fatigue resistance and reversibility under several repeated reversible isomerization cycles. The cis-to-trans photoisomerization of 4 can be not only achieved by irradiation at UV lignt, but also realized by a more efficient way of change the state of redox center. Our study will provide a good basis for research in design new type of multiple-response molecular switches.
2019, 39(7): 2026-2034
doi: 10.6023/cjoc201812019
Abstract:
In order to study the Strecker reaction of multi-substituted amino armorotic heterocycles and the biological activity of the target compounds, the reaction of 3, 5-disubstituted pyrazole-4-amine, TMSCN and aldehydes was realized for the first time by the catalysis of anhydrous ZnI2 with 4 molecular seive. The reaction condition was preliminarily optimized and the substrate scop of aldehydes was studied. 20 target compounds of cyano-containing multi-substituted pyrazoles were obtained with the highest yield of 93.5%, and the sturctures of the compounds were confirmed via 1H NMR, 13C NMR and HRMS methods. Priliminary bioassay of the target compounds showed that 13 target compounds possessed 100% larvicidal activity against mosquito at a concentration of 10×10-3 g/L, and four compounds possessed over 40% larvicidal activity at 5×10-3 g/L, and 10 compounds poccessed weak larvicidal activity against army worm at 500×10-3 g/L with the highest activity of 40%; five compounds were confirmed poccessed good inactivation activity against tobacco mosaic virus (TMV) in vivo with the highest inhibition rate of 31.8%, and four compounds possessed moderate host-protection activity against TMV in vivo with the highest rate of 28.3%; in addition, at a concentration of 50×10-3 g/L, three compounds showed moderate fungicidal activity against Pythium aphanidermatum, Phomopsis asparagi, Phytophora capsic and Rhizoctonia solani in vitro. 4-((1-cyanododecyl)amino)-5-ethyl-N-methyl-1H-pyrazole-3-carboxamide (3t) possessed the highest activity against Phytophora capsic of 62.3%. All the results showed that 3, 5-disubstitued pyrazole-4-amine could undergo Strecker reaction smoothly, and this study gave a useful example to explore the Strecker reaction of other multi-substituted aromatic hetreocyclic amines. Additionally, the larvicidal and anti-TMV activity of the target compounds gave some clues in design cyano-containing biological heterocycles.
In order to study the Strecker reaction of multi-substituted amino armorotic heterocycles and the biological activity of the target compounds, the reaction of 3, 5-disubstituted pyrazole-4-amine, TMSCN and aldehydes was realized for the first time by the catalysis of anhydrous ZnI2 with 4 molecular seive. The reaction condition was preliminarily optimized and the substrate scop of aldehydes was studied. 20 target compounds of cyano-containing multi-substituted pyrazoles were obtained with the highest yield of 93.5%, and the sturctures of the compounds were confirmed via 1H NMR, 13C NMR and HRMS methods. Priliminary bioassay of the target compounds showed that 13 target compounds possessed 100% larvicidal activity against mosquito at a concentration of 10×10-3 g/L, and four compounds possessed over 40% larvicidal activity at 5×10-3 g/L, and 10 compounds poccessed weak larvicidal activity against army worm at 500×10-3 g/L with the highest activity of 40%; five compounds were confirmed poccessed good inactivation activity against tobacco mosaic virus (TMV) in vivo with the highest inhibition rate of 31.8%, and four compounds possessed moderate host-protection activity against TMV in vivo with the highest rate of 28.3%; in addition, at a concentration of 50×10-3 g/L, three compounds showed moderate fungicidal activity against Pythium aphanidermatum, Phomopsis asparagi, Phytophora capsic and Rhizoctonia solani in vitro. 4-((1-cyanododecyl)amino)-5-ethyl-N-methyl-1H-pyrazole-3-carboxamide (3t) possessed the highest activity against Phytophora capsic of 62.3%. All the results showed that 3, 5-disubstitued pyrazole-4-amine could undergo Strecker reaction smoothly, and this study gave a useful example to explore the Strecker reaction of other multi-substituted aromatic hetreocyclic amines. Additionally, the larvicidal and anti-TMV activity of the target compounds gave some clues in design cyano-containing biological heterocycles.
2019, 39(7): 1930-1938
doi: 10.6023/cjoc201901038
Abstract:
A new diarylethene 1-(3, 5-dimethylisoxazole-4-yl)-2-(2-methyl-5-[(3-aminonaphthol-2-yl)phenol-yl]-thiophene-3-yl)perfluorocyclopentene (1O) dual-response chemosensor has been synthesized, and its photochromic and fluorescent switch behaviors were systematically investigated by stimulation of lights and ions. The results indicated that 1O could serve as a CN-/F- "naked-eyes" colorimetric sensor with the color change from colorless to yellow, and act as a "Turn-on" fluorescence probe for specific detecting Zn2+. Moreover, the limits of detection of CN- and Zn2+ were determined to be 1.03×10-6 and 2.98×10-8 mol·L-1, respectively.
A new diarylethene 1-(3, 5-dimethylisoxazole-4-yl)-2-(2-methyl-5-[(3-aminonaphthol-2-yl)phenol-yl]-thiophene-3-yl)perfluorocyclopentene (1O) dual-response chemosensor has been synthesized, and its photochromic and fluorescent switch behaviors were systematically investigated by stimulation of lights and ions. The results indicated that 1O could serve as a CN-/F- "naked-eyes" colorimetric sensor with the color change from colorless to yellow, and act as a "Turn-on" fluorescence probe for specific detecting Zn2+. Moreover, the limits of detection of CN- and Zn2+ were determined to be 1.03×10-6 and 2.98×10-8 mol·L-1, respectively.
2019, 39(7): 1953-1961
doi: 10.6023/cjoc201812037
Abstract:
Based on the listed drug rebamipide, a series of novel compounds of phenylpropenoyl-amino acid structures were designed and synthesized according to the pharmacophore-combination strategy. The structures of the target compounds were confirmed by NMR and MS. The inhibitory activities against IL-6 and TNF-α had been investigated. The results demonstrated that all compounds exhibited moderate IL-6 and TNF-α inhibitory activities. In particular, the activities of four compounds were significantly improved than that of rebamipide.
Based on the listed drug rebamipide, a series of novel compounds of phenylpropenoyl-amino acid structures were designed and synthesized according to the pharmacophore-combination strategy. The structures of the target compounds were confirmed by NMR and MS. The inhibitory activities against IL-6 and TNF-α had been investigated. The results demonstrated that all compounds exhibited moderate IL-6 and TNF-α inhibitory activities. In particular, the activities of four compounds were significantly improved than that of rebamipide.
2019, 39(7): 1983-1989
doi: 10.6023/cjoc201812036
Abstract:
A series of novel chidamide based histone deacetylases (HDACs) inhibitors were rationally designed and synthesized to increase the Zn2+ chelating and selectivity. Biological characterization established that most of the compounds showed moderate antiproliferative activitites in cancer cell lines. Among the tested analogs, (E)-N-(4-amino-6- fluoro-[1, 1'-biphenyl]-3-yl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7i) and (E)-N-(2-amino-4-fluoro-5-(thiophen- 2-yl)phenyl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7j) exhibit the most potent antiproliferative activity with IC50 of 3.29 and 2.59 μmol/L in Jurkat cells, respectively. Furthermore, these two compounds have a certain HDAC inhibitory activity. Collectively, the results partly encourage further development of more potential analogs based on chidamide.
A series of novel chidamide based histone deacetylases (HDACs) inhibitors were rationally designed and synthesized to increase the Zn2+ chelating and selectivity. Biological characterization established that most of the compounds showed moderate antiproliferative activitites in cancer cell lines. Among the tested analogs, (E)-N-(4-amino-6- fluoro-[1, 1'-biphenyl]-3-yl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7i) and (E)-N-(2-amino-4-fluoro-5-(thiophen- 2-yl)phenyl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide (7j) exhibit the most potent antiproliferative activity with IC50 of 3.29 and 2.59 μmol/L in Jurkat cells, respectively. Furthermore, these two compounds have a certain HDAC inhibitory activity. Collectively, the results partly encourage further development of more potential analogs based on chidamide.
2019, 39(7): 2001-2008
doi: 10.6023/cjoc201902011
Abstract:
The aromatic amine functionality occupies a very important role in organic chemistry due to its prominence in biological and naturally occurring molecules. In addition, the synthesized secondary aromatic amines with pendant boronate ester are versatile intermediates in several organic transformations. The one-pot, two-step reductive amination of boron-containing primary aromatic amines and aldehydes has been achieved in the presence of NaOH in ethanol using B2pin2 as reductant. After extensive screening of various reaction parameters, such as base, reaction temperature, solvent, reaction time and protective gas, a series of secondary aromatic amines with pendant boronate ester and various functional groups were obtained in moderate to good yields under the optimal reaction conditions. This system features generally high yields and broad functional group tolerance. The boronate ester substituent is a very good handle to be further functionalized.
The aromatic amine functionality occupies a very important role in organic chemistry due to its prominence in biological and naturally occurring molecules. In addition, the synthesized secondary aromatic amines with pendant boronate ester are versatile intermediates in several organic transformations. The one-pot, two-step reductive amination of boron-containing primary aromatic amines and aldehydes has been achieved in the presence of NaOH in ethanol using B2pin2 as reductant. After extensive screening of various reaction parameters, such as base, reaction temperature, solvent, reaction time and protective gas, a series of secondary aromatic amines with pendant boronate ester and various functional groups were obtained in moderate to good yields under the optimal reaction conditions. This system features generally high yields and broad functional group tolerance. The boronate ester substituent is a very good handle to be further functionalized.
2019, 39(7): 2018-2025
doi: 10.6023/cjoc201901026
Abstract:
A series of aldo-quinazolinones were synthesized by a one-pot iodine-induced oxidative condensation of the unprotected mono-/di-saccharides and o-aminobenzamides in the yields of 30%~80%, providing an effective protocol for the preparation of aldo-quinazolinones. The amount of iodine has an important effect on the reaction.
A series of aldo-quinazolinones were synthesized by a one-pot iodine-induced oxidative condensation of the unprotected mono-/di-saccharides and o-aminobenzamides in the yields of 30%~80%, providing an effective protocol for the preparation of aldo-quinazolinones. The amount of iodine has an important effect on the reaction.
2019, 39(7): 2035-2041
doi: 10.6023/cjoc201811009
Abstract:
The synthetic route of allyl-methyl-N-pantothenamide (1) featuring[2,3]-Wittig rearrangement and palladium catalyzed formate reduction to assemble the requisite quaternary carbon with adjacent secondary alcohol has been reported. Our strategy presents a facile synthetic route to access 1 in 10 steps, which also provide a novel inspiration to construct chiral quaternary carbon via asymmetrical[2,3]-Wittig rearrangement.
The synthetic route of allyl-methyl-N-pantothenamide (1) featuring[2,3]-Wittig rearrangement and palladium catalyzed formate reduction to assemble the requisite quaternary carbon with adjacent secondary alcohol has been reported. Our strategy presents a facile synthetic route to access 1 in 10 steps, which also provide a novel inspiration to construct chiral quaternary carbon via asymmetrical[2,3]-Wittig rearrangement.
2019, 39(7): 2042-2047
doi: 10.6023/cjoc201901012
Abstract:
O-Acylation of 1, 3-dicarbonyl compounds provides enol esters which act as precursors for the synthesis of chiral alcohols, natural products, heterocycles and functional materials. Perfluoroalkanosulfonyl fluoride (RfSO2F) is a class of excellent hydroxyl-activating reagent, and has been extensively developed and used in the formation of C-F, C-O, C-N and C-S bonds in organic synthesis. In this work one-step O-acylation of 1, 3-dicarbonyl compounds (1, 3-diketones and β-ketonic esters) with carboxylic acids activated by RfSO2F in alkaline media was disclosed, and the corresponding O-acylation products (enol esters) were generated in moderate to good yields. The optimized reaction conditions are as follows:1, 8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as base, CH2Cl2 as solvent, n-C4F9SO2F as activating reagent, room temperature for 30 min and the molar ratio of n(1, 3-dicarbonyls):n(RCOOH):n(RfSO2F):n(DBU) being 1.0:1.0:1.0:4.0. A novel reagent for one-step O-acylation of 1, 3-dicarbonyl compounds with carboxylic acids was developed. The application of RfSO2F in organic synthesis was further expanded.
O-Acylation of 1, 3-dicarbonyl compounds provides enol esters which act as precursors for the synthesis of chiral alcohols, natural products, heterocycles and functional materials. Perfluoroalkanosulfonyl fluoride (RfSO2F) is a class of excellent hydroxyl-activating reagent, and has been extensively developed and used in the formation of C-F, C-O, C-N and C-S bonds in organic synthesis. In this work one-step O-acylation of 1, 3-dicarbonyl compounds (1, 3-diketones and β-ketonic esters) with carboxylic acids activated by RfSO2F in alkaline media was disclosed, and the corresponding O-acylation products (enol esters) were generated in moderate to good yields. The optimized reaction conditions are as follows:1, 8-diazabicyclo-[5.4.0]undec-7-ene (DBU) as base, CH2Cl2 as solvent, n-C4F9SO2F as activating reagent, room temperature for 30 min and the molar ratio of n(1, 3-dicarbonyls):n(RCOOH):n(RfSO2F):n(DBU) being 1.0:1.0:1.0:4.0. A novel reagent for one-step O-acylation of 1, 3-dicarbonyl compounds with carboxylic acids was developed. The application of RfSO2F in organic synthesis was further expanded.
2019, 39(7): 2048-2052
doi: 10.6023/cjoc201812045
Abstract:
In the presence of 20 mol% K2S2O8, a variety of 3-aryltellurylindoles were obtained in high yields via the telluration of indole dervatives with diarylditellurides catalyzed by 20 mol% I2. This process tolerates a wide spectrum of different indole derivatives and diarylditellurides. Other advantages include mild reaction conditions, high yields and atom economy, and an efficient route to 3-aryltellurylindoles is afforded.
In the presence of 20 mol% K2S2O8, a variety of 3-aryltellurylindoles were obtained in high yields via the telluration of indole dervatives with diarylditellurides catalyzed by 20 mol% I2. This process tolerates a wide spectrum of different indole derivatives and diarylditellurides. Other advantages include mild reaction conditions, high yields and atom economy, and an efficient route to 3-aryltellurylindoles is afforded.
2019, 39(7): 2053-2061
doi: 10.6023/cjoc201902027
Abstract:
Eighteen novel pyrazole oxime ethers containing 1, 2, 4-triazole moiety were designed and synthesized according to the method of active substructure combination. Their structures were characterized by 1H NMR, 13C NMR, and elemental analyses. Preliminary bioassay showed that some target compounds showed good insecticidal activities against Oriental armyworm, Aphis medicaginis and Tetranychus cinnabarinus. At the concentration of 500 μg/mL, target compounds had insecticidal activity against Oriental armyworm with 90%~100%, which were similar to the control of avermectin, four compounds showed 100% insecticidal activity against Aphis medicaginis, which were similar to imidacloprid. The lethal rate of 1- methyl-3-methyl-5-(3, 5-difluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-[4-(1H-1, 2, 4-triazol-1-yl)phenylmethyl]oxime (8p) against Tetranychus cinnabarinus was 100%, which was similar to that of fenpyroximate. When the concentration was reduced to 100 μg/mL, six compounds exhibited insecticidal activity against Oriental armyworm with 90%~100%, three compounds showed insecticidal activity against Aphis medicaginis with 80%~100%, and compound 8p had acaricidal activity against Tetranychus cinnabarinus with 80%. At the concentration of 20 μg/mL, the lethal rates of two compounds against Oriental armyworm were 75% and 70%, respectively. Additionally, some compounds exhibited certain anti-tumor activity against human hepatocellular carcinoma SMMC-7721 cells.
Eighteen novel pyrazole oxime ethers containing 1, 2, 4-triazole moiety were designed and synthesized according to the method of active substructure combination. Their structures were characterized by 1H NMR, 13C NMR, and elemental analyses. Preliminary bioassay showed that some target compounds showed good insecticidal activities against Oriental armyworm, Aphis medicaginis and Tetranychus cinnabarinus. At the concentration of 500 μg/mL, target compounds had insecticidal activity against Oriental armyworm with 90%~100%, which were similar to the control of avermectin, four compounds showed 100% insecticidal activity against Aphis medicaginis, which were similar to imidacloprid. The lethal rate of 1- methyl-3-methyl-5-(3, 5-difluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-[4-(1H-1, 2, 4-triazol-1-yl)phenylmethyl]oxime (8p) against Tetranychus cinnabarinus was 100%, which was similar to that of fenpyroximate. When the concentration was reduced to 100 μg/mL, six compounds exhibited insecticidal activity against Oriental armyworm with 90%~100%, three compounds showed insecticidal activity against Aphis medicaginis with 80%~100%, and compound 8p had acaricidal activity against Tetranychus cinnabarinus with 80%. At the concentration of 20 μg/mL, the lethal rates of two compounds against Oriental armyworm were 75% and 70%, respectively. Additionally, some compounds exhibited certain anti-tumor activity against human hepatocellular carcinoma SMMC-7721 cells.
2019, 39(7): 2070-2074
doi: 10.6023/cjoc201812039
Abstract:
In order to discover high activity lead compound, based on our previous studies, a series of terpinen-4-ol deri- vatives containing oxime ether were designed and synthesized. The bioassay results showed that the target compounds displayed good insecticidal activity against Mythimna separata (Walker). Especially, compound 3a exhibited satisfied activity with the LD50 value of 0.0054 mg/insect, which is 19.1 times than terpinen-4-ol. As a high activity compound with simple structure, 2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-prop-2-yn-1-yl oxime (3a) could be a lead compound for further study.
In order to discover high activity lead compound, based on our previous studies, a series of terpinen-4-ol deri- vatives containing oxime ether were designed and synthesized. The bioassay results showed that the target compounds displayed good insecticidal activity against Mythimna separata (Walker). Especially, compound 3a exhibited satisfied activity with the LD50 value of 0.0054 mg/insect, which is 19.1 times than terpinen-4-ol. As a high activity compound with simple structure, 2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one O-prop-2-yn-1-yl oxime (3a) could be a lead compound for further study.
2019, 39(7): 2075-2083
doi: 10.6023/cjoc201901052
Abstract:
The regioselectivity of N-heterocyclic carbene (NHC)-catalyzed[3+3] annulation of α-bromoenal with enaminone is dependent on the temperature. The reactions performed at 35℃ could regiospecifically give the derivatives of fused pyranone instead of previously reported quinolones, which provided a new shortcut to pyranone with mild reaction condition, broad substrate scope, high yields and operational simplicity.
The regioselectivity of N-heterocyclic carbene (NHC)-catalyzed[3+3] annulation of α-bromoenal with enaminone is dependent on the temperature. The reactions performed at 35℃ could regiospecifically give the derivatives of fused pyranone instead of previously reported quinolones, which provided a new shortcut to pyranone with mild reaction condition, broad substrate scope, high yields and operational simplicity.
2019, 39(7): 2089-2093
doi: 10.6023/cjoc201812047
Abstract:
A near-infrared fluorescence probe CS-Cys was synthesized using rhodamine analoguse as near-infrared fluorescent group. The probe can specifically response to Cys, not to other sulfhydryl amino acids. The response mechanism is that Cys reacts with the acrylic ester of CS-Cys and the conjugated addition-cyclization reaction occurs, then the hydroxyl groups are exposed and fluorescence is released. Through studying the fluorescence changes of CS-Cys and Cys in different pH environments, it was found that the donor ability of the electron-donor group and the process of the ICT could be monitored by changing the pH of probe solution, and the fluorescence excitation wavelength and the emission wavelength could be adjusted to the near infrared region.
A near-infrared fluorescence probe CS-Cys was synthesized using rhodamine analoguse as near-infrared fluorescent group. The probe can specifically response to Cys, not to other sulfhydryl amino acids. The response mechanism is that Cys reacts with the acrylic ester of CS-Cys and the conjugated addition-cyclization reaction occurs, then the hydroxyl groups are exposed and fluorescence is released. Through studying the fluorescence changes of CS-Cys and Cys in different pH environments, it was found that the donor ability of the electron-donor group and the process of the ICT could be monitored by changing the pH of probe solution, and the fluorescence excitation wavelength and the emission wavelength could be adjusted to the near infrared region.
2019, 39(7): 2094-2098
doi: 10.6023/cjoc201901010
Abstract:
Parvistemonine A was isolated from Stemona parviflora. The total synthesis of racemic parvistemonine A was completed in 6 steps for the first time, employing compound 7 as the starting material. The synthetic strategy features a tandem Friedel-Crafts cyclization and lactonization, Vilsmeier-Haack and Julia-Kocienski olefination. This study laid the foundation for the synthesis of the parvistemonine A derivative and its biological activity research.
Parvistemonine A was isolated from Stemona parviflora. The total synthesis of racemic parvistemonine A was completed in 6 steps for the first time, employing compound 7 as the starting material. The synthetic strategy features a tandem Friedel-Crafts cyclization and lactonization, Vilsmeier-Haack and Julia-Kocienski olefination. This study laid the foundation for the synthesis of the parvistemonine A derivative and its biological activity research.
2019, 39(7): 2099-2105
doi: 10.6023/cjoc201812027
Abstract:
The structure of thiazolidine piperidine could affect the metabolic activitives of cholesterol compounds in vivo, and it is the key pharmacophore of oxythiazolidine to inhibit the oxygen cholesterol-binding protein (OSBP) of pathogenic bacteria. 14 novel thiazolidine piperidine nicotinamide derivatives were designed and synthesized in search of new bioactive compounds containing thiazolidine piperidine structure. The structures of target compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. The preliminary bioassay showed that the target compounds generally had antibacterial activities. At the concentration of 100 μg/mL, the antibacterial activity of one compound against Fusarium graminearum was 60%, the antibacterial activities of three compounds against Botrytis cinerea were 60%, the bacteriostatical activities of six compounds aganist Diplocarpon mali were 70%, and the antibacterial activity of (4-(5-(2, 3-dichlorophenyl)-4-methylthiazol-2- yl)piperidin-1-yl)(5, 6-dichloropyridin-3-yl)methanone (6k) against Phytophthora infestans (Mont.) de Bary was 75%. There- fore it was worth for further research about structural optimization.
The structure of thiazolidine piperidine could affect the metabolic activitives of cholesterol compounds in vivo, and it is the key pharmacophore of oxythiazolidine to inhibit the oxygen cholesterol-binding protein (OSBP) of pathogenic bacteria. 14 novel thiazolidine piperidine nicotinamide derivatives were designed and synthesized in search of new bioactive compounds containing thiazolidine piperidine structure. The structures of target compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. The preliminary bioassay showed that the target compounds generally had antibacterial activities. At the concentration of 100 μg/mL, the antibacterial activity of one compound against Fusarium graminearum was 60%, the antibacterial activities of three compounds against Botrytis cinerea were 60%, the bacteriostatical activities of six compounds aganist Diplocarpon mali were 70%, and the antibacterial activity of (4-(5-(2, 3-dichlorophenyl)-4-methylthiazol-2- yl)piperidin-1-yl)(5, 6-dichloropyridin-3-yl)methanone (6k) against Phytophthora infestans (Mont.) de Bary was 75%. There- fore it was worth for further research about structural optimization.
2019, 39(7): 2106-2116
doi: 10.6023/cjoc201811020
Abstract:
Protein tyrosine phosphatase-1B (PTP1B) is recognized as a potent target for the therapy of diabetes. Lithocolic acid (LCA), a kind of endogenic steroid, was reported as a moderate PTP1B inhibitor. In this paper, 3-hydroxyl of LCA was oxidized, followed by oximating and splicing with cinnamoyl to afford a novel series of derivatives, which were characterized by 1H NMR, 13C NMR and HRMS spectra. The results of bioassays exhibited that most of the titled compounds were active to PTP1B. Among them, compound 12b, the most potent one, has an IC50 of 0.79 µmol•L-1, about 15-fold more potent than the lead compound. Besides, it also has a selectivity of about 4-fold over T-cell protein tyrosine phosphatase (TCPTP).
Protein tyrosine phosphatase-1B (PTP1B) is recognized as a potent target for the therapy of diabetes. Lithocolic acid (LCA), a kind of endogenic steroid, was reported as a moderate PTP1B inhibitor. In this paper, 3-hydroxyl of LCA was oxidized, followed by oximating and splicing with cinnamoyl to afford a novel series of derivatives, which were characterized by 1H NMR, 13C NMR and HRMS spectra. The results of bioassays exhibited that most of the titled compounds were active to PTP1B. Among them, compound 12b, the most potent one, has an IC50 of 0.79 µmol•L-1, about 15-fold more potent than the lead compound. Besides, it also has a selectivity of about 4-fold over T-cell protein tyrosine phosphatase (TCPTP).
2019, 39(7): 2062-2069
doi: 10.6023/cjoc201901009
Abstract:
In order to explore the structure of lead compounds with biological activities, using oxathiapiprolin as a template, sixteen oxathiapiprolin derivatives were designed and synthesized to study the influences of substituent to the fungicidal activities which connected with carbon (No. 5 carbon) near the sulfur on the thiazole ring. All the structures were confirmed by 1H NMR, 13C NMR and HRMS. Preliminary bioassay showed that the target compounds generally had fungicidal activitives in vitro at a concentration of 100 μg/mL, the fungicidal activities of 1-(4-(4-cyclopropyl-5-(2-fluorophenyl)thiazol-2-yl)piperidin- 1-yl)-2-(5-methyl-3-trifluoromethyl-1H-pyrazol-1-yl)ethan-1-one (9o) against Fusarium graminearum was 60%, the fungicidal activities of six target compounds against Diplocarpon mali were 70%, the fungicidal activities of four target compounds against Phytophthora infestans were 50%, and the fungicidal activities of 2-(5-methyl-3-trifluoromethyl-1H-pyrazol-1- yl)-1-(4-(4-methyl-5-(m-tolyl)thiazol-2-yl)piperidin-1-yl)ethan-1-one (9h) against Botrytis cinerea was 75%. In addtion, the fungicidal activities of the target compounds aganist Diplocarpon mali and Botrytis cinerea at 100 μg/mL were higher to azoxystrobin at 50 μg/mL.
In order to explore the structure of lead compounds with biological activities, using oxathiapiprolin as a template, sixteen oxathiapiprolin derivatives were designed and synthesized to study the influences of substituent to the fungicidal activities which connected with carbon (No. 5 carbon) near the sulfur on the thiazole ring. All the structures were confirmed by 1H NMR, 13C NMR and HRMS. Preliminary bioassay showed that the target compounds generally had fungicidal activitives in vitro at a concentration of 100 μg/mL, the fungicidal activities of 1-(4-(4-cyclopropyl-5-(2-fluorophenyl)thiazol-2-yl)piperidin- 1-yl)-2-(5-methyl-3-trifluoromethyl-1H-pyrazol-1-yl)ethan-1-one (9o) against Fusarium graminearum was 60%, the fungicidal activities of six target compounds against Diplocarpon mali were 70%, the fungicidal activities of four target compounds against Phytophthora infestans were 50%, and the fungicidal activities of 2-(5-methyl-3-trifluoromethyl-1H-pyrazol-1- yl)-1-(4-(4-methyl-5-(m-tolyl)thiazol-2-yl)piperidin-1-yl)ethan-1-one (9h) against Botrytis cinerea was 75%. In addtion, the fungicidal activities of the target compounds aganist Diplocarpon mali and Botrytis cinerea at 100 μg/mL were higher to azoxystrobin at 50 μg/mL.
2019, 39(7): 2084-2088
doi: 10.6023/cjoc201810004
Abstract:
A convenient approach for the synthesis of β-substituted α, β-unsaturated carbonyl porphyrin compounds via base-catalyzed aldol reaction was developed. By this method, a series of β-substituted α, β-unsaturated carbonyl porphyrin compounds were constructed using β-porphyrin formaldehyde and ketones with moderate to excellent yields under mild reaction conditions, especially solvent-free, and good functional group tolerance. Furthermore, this process was successfully applied to the reactions of different metal porphyrin which have been reported to have poor reaction effects with good yields.
A convenient approach for the synthesis of β-substituted α, β-unsaturated carbonyl porphyrin compounds via base-catalyzed aldol reaction was developed. By this method, a series of β-substituted α, β-unsaturated carbonyl porphyrin compounds were constructed using β-porphyrin formaldehyde and ketones with moderate to excellent yields under mild reaction conditions, especially solvent-free, and good functional group tolerance. Furthermore, this process was successfully applied to the reactions of different metal porphyrin which have been reported to have poor reaction effects with good yields.
