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2019 Volume 39 Issue 3
2019, 39(3): 573-590
doi: 10.6023/cjoc201809004
Abstract:
Heterocycles are ubiquitous in natural products, pharmaceuticals, organic materials, and numerous functional molecules. These structural units probably constitute the largest and most varied family of organic compounds. Hence the development of new procedures for heterocycles synthesis has been a hot research topic for over centuries. Among all the new synthetic methods, transition-metal-catalyzed reactions are attractive. Those reactions can formulate complicated heterocycles efficiently from available starting materials under mild conditions and atom economical routes. Among them, transition-metal-catalyzed carbonylation reaction has become an efficient and useful tool in organic synthesis since the first hydroformylation reaction developed by W. Reppe at BASF in the 1930s. Since then impressive progress has been achieved in this area. In nowadays, various types of carbonylation reactions were established. Substrates including aryl halides, olefins, alkynes or simply C-H bond can be activated and produce the corresponding carbonyl-containing compounds smoothly. On the other hand, carbon monoxide was discovered and identified in the 18th century. Since the first applications in industry around 80 years ago, academic and industrial laboratories have explored uses of CO in chemical reactions broadly. However, because of the special physical properties of CO, organic chemists were often reluctant to apply carbonylations frequently in laboratories. Hence, different kinds of CO surrogates were developed and applied in carbonylation reactions, such as metal carbonyl compounds M(CO)x, formates, alcohols, formic acid, aldehyde, biomass and carbon dioxide. Those CO surrogates offer interesting opportunities for carbonylation reactions. This account mainly outlines our progress in the development of transition-metal-catalyzed carbonylative synthesis and functionalization of heterocycles from 2012 to 2018. With copper, palladium, rhodium, ruthenium and iridium as the catalysts and relying on the activation of carbon-halogen and carbon-hydrogen bonds, we are able to synthesis various of heterocycles by using CO gas or CO surrogates as the C1 building blocks.
Heterocycles are ubiquitous in natural products, pharmaceuticals, organic materials, and numerous functional molecules. These structural units probably constitute the largest and most varied family of organic compounds. Hence the development of new procedures for heterocycles synthesis has been a hot research topic for over centuries. Among all the new synthetic methods, transition-metal-catalyzed reactions are attractive. Those reactions can formulate complicated heterocycles efficiently from available starting materials under mild conditions and atom economical routes. Among them, transition-metal-catalyzed carbonylation reaction has become an efficient and useful tool in organic synthesis since the first hydroformylation reaction developed by W. Reppe at BASF in the 1930s. Since then impressive progress has been achieved in this area. In nowadays, various types of carbonylation reactions were established. Substrates including aryl halides, olefins, alkynes or simply C-H bond can be activated and produce the corresponding carbonyl-containing compounds smoothly. On the other hand, carbon monoxide was discovered and identified in the 18th century. Since the first applications in industry around 80 years ago, academic and industrial laboratories have explored uses of CO in chemical reactions broadly. However, because of the special physical properties of CO, organic chemists were often reluctant to apply carbonylations frequently in laboratories. Hence, different kinds of CO surrogates were developed and applied in carbonylation reactions, such as metal carbonyl compounds M(CO)x, formates, alcohols, formic acid, aldehyde, biomass and carbon dioxide. Those CO surrogates offer interesting opportunities for carbonylation reactions. This account mainly outlines our progress in the development of transition-metal-catalyzed carbonylative synthesis and functionalization of heterocycles from 2012 to 2018. With copper, palladium, rhodium, ruthenium and iridium as the catalysts and relying on the activation of carbon-halogen and carbon-hydrogen bonds, we are able to synthesis various of heterocycles by using CO gas or CO surrogates as the C1 building blocks.
2019, 39(3): 591-616
doi: 10.6023/cjoc201810013
Abstract:
Reactive nitrogen and reactive oxygen are chemical substances with strong biological activity. In human cells, peroxides can be generated due to enzymatic or non-enzymatic processes. Abnormal levels of peroxide can cause oxidative damage and aging and various diseases such as cardiovascular disease, neurological diseases, Alzheimer's disease, Parkinson's disease and even cancer. In order to effectively cure these diseases, health workers must find the source of the problem. Currently, there is no better way to detect reactive oxygen species and reactive nitrogen. Fluorescence spectrometry in recent years becomes the preferred method for the majority of researchers for detecting active oxygen and reactive nitrogen. Therefore, the development of selective recognition and high sensitivity molecular fluorescent probes to achieve effective detection of reactive nitrogen and reactive oxygen species is of great significance. On one hand, molecular fluorescent probe detecting and imaging technology has excellent characteristics such as high sensitivity, strong selectivity, small damage and good cell compatibility. On the other hand, fluorescent probes play an important role in the pathophysiological process of reactive nitrogen and reactive oxygen species. Therefore, the fluorescent probe method is widely used in the fields of biology and medicine. However, due to the inherent specificity of reactive nitrogen and reactive oxygen species, it has become an urgent problem for researchers, such as high reactivity, short cycle, etc. In order to overcome the shortcomings of fluorescent probe analysis, researchers are constantly striving to find better active fluorescent probes for the detection of reactive nitrogen and reactive oxygen species. Recent evolutions in the development of molecular fluorescent probes for the detection of active nitrogen and reactive oxygen species and cell imaging work are reviewed. Finally, a new type of molecular fluorescent probe is proposed to be used for the challenge of active nitrogen and active oxygen detection, and the future development direction and prospect.
Reactive nitrogen and reactive oxygen are chemical substances with strong biological activity. In human cells, peroxides can be generated due to enzymatic or non-enzymatic processes. Abnormal levels of peroxide can cause oxidative damage and aging and various diseases such as cardiovascular disease, neurological diseases, Alzheimer's disease, Parkinson's disease and even cancer. In order to effectively cure these diseases, health workers must find the source of the problem. Currently, there is no better way to detect reactive oxygen species and reactive nitrogen. Fluorescence spectrometry in recent years becomes the preferred method for the majority of researchers for detecting active oxygen and reactive nitrogen. Therefore, the development of selective recognition and high sensitivity molecular fluorescent probes to achieve effective detection of reactive nitrogen and reactive oxygen species is of great significance. On one hand, molecular fluorescent probe detecting and imaging technology has excellent characteristics such as high sensitivity, strong selectivity, small damage and good cell compatibility. On the other hand, fluorescent probes play an important role in the pathophysiological process of reactive nitrogen and reactive oxygen species. Therefore, the fluorescent probe method is widely used in the fields of biology and medicine. However, due to the inherent specificity of reactive nitrogen and reactive oxygen species, it has become an urgent problem for researchers, such as high reactivity, short cycle, etc. In order to overcome the shortcomings of fluorescent probe analysis, researchers are constantly striving to find better active fluorescent probes for the detection of reactive nitrogen and reactive oxygen species. Recent evolutions in the development of molecular fluorescent probes for the detection of active nitrogen and reactive oxygen species and cell imaging work are reviewed. Finally, a new type of molecular fluorescent probe is proposed to be used for the challenge of active nitrogen and active oxygen detection, and the future development direction and prospect.
2019, 39(3): 617-624
doi: 10.6023/cjoc201809030
Abstract:
Sodium sulfinates (RSO2Na) is a kind of reagents with stable properties, simple synthesis and low price, which has been widely used in the field of organic synthesis chemistry. The recent progress (2014~2018) on synthesis of sulfur compounds by sodium sulfinates is summarized. In addition, the organic reactions on the building of S-X (S-S, S-N and S-P bond) and other types of reactions 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 sodium sulfinates.
Sodium sulfinates (RSO2Na) is a kind of reagents with stable properties, simple synthesis and low price, which has been widely used in the field of organic synthesis chemistry. The recent progress (2014~2018) on synthesis of sulfur compounds by sodium sulfinates is summarized. In addition, the organic reactions on the building of S-X (S-S, S-N and S-P bond) and other types of reactions 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 sodium sulfinates.
2019, 39(3): 625-647
doi: 10.6023/cjoc201808031
Abstract:
As an important kind of organic chemical reaction, difunctionalization of alkenes can not only synthesize multi-site reaction products effectively in one step, but also transform the starting material into other compounds that containing biological activity or drug activity. At the same time, it provides more methods for the construction of chemical structure diversity, so it is very important to develop the bifunctionalization of alkenes. In this paper, the bifunctionalization of various alkenes in recent 12 years is reviewed. It can be divided into three parts:copper-catalyzed difunctionalization of alkenes, other transition metal-catalyzed difunctionalization of alkenes, and non-metal-catalyzed difunctionalization of alkenes. The prospects of this reaction are also discussed.
As an important kind of organic chemical reaction, difunctionalization of alkenes can not only synthesize multi-site reaction products effectively in one step, but also transform the starting material into other compounds that containing biological activity or drug activity. At the same time, it provides more methods for the construction of chemical structure diversity, so it is very important to develop the bifunctionalization of alkenes. In this paper, the bifunctionalization of various alkenes in recent 12 years is reviewed. It can be divided into three parts:copper-catalyzed difunctionalization of alkenes, other transition metal-catalyzed difunctionalization of alkenes, and non-metal-catalyzed difunctionalization of alkenes. The prospects of this reaction are also discussed.
2019, 39(3): 648-660
doi: 10.6023/cjoc201807056
Abstract:
Polyethylene glycols (PEG) can dissolve a lot of organic compounds and metallic complexes. Moreover, they are thermally stable, nonvolatile, non-toxic, biodegradable, inexpensive and recyclable. Thus, PEG as green medium has been successfully employed in many organic reactions, such as carbon-carbon coupling reaction, carbon-hetero coupling reaction, multicomponent reaction, condensation reaction, addition reaction, substitution reaction, oxidation reaction, reductive reaction, and so on. The recent advances of PEG applied in orgainc synthesis are reviewed.
Polyethylene glycols (PEG) can dissolve a lot of organic compounds and metallic complexes. Moreover, they are thermally stable, nonvolatile, non-toxic, biodegradable, inexpensive and recyclable. Thus, PEG as green medium has been successfully employed in many organic reactions, such as carbon-carbon coupling reaction, carbon-hetero coupling reaction, multicomponent reaction, condensation reaction, addition reaction, substitution reaction, oxidation reaction, reductive reaction, and so on. The recent advances of PEG applied in orgainc synthesis are reviewed.
2019, 39(3): 661-667
doi: 10.6023/cjoc201808015
Abstract:
Construction of C-N bond is one of the most important areas in synthetic organic chemistry and medical chemistry. Many synthetic methods for the construction of C-N bond have been reported over the past few years. Copper-catalyzed Chan-Lam reactions represent one of the most powerful and straightforward tools to construct C-N bonds. In this paper, the recent progress in Chan-Lam coupling of N-compounds with (hetero) aryl boronates to construct C-N bond based on the reaction mechanism, reaction system, the scope of substrates, etc., is reviewed.
Construction of C-N bond is one of the most important areas in synthetic organic chemistry and medical chemistry. Many synthetic methods for the construction of C-N bond have been reported over the past few years. Copper-catalyzed Chan-Lam reactions represent one of the most powerful and straightforward tools to construct C-N bonds. In this paper, the recent progress in Chan-Lam coupling of N-compounds with (hetero) aryl boronates to construct C-N bond based on the reaction mechanism, reaction system, the scope of substrates, etc., is reviewed.
2019, 39(3): 668-678
doi: 10.6023/cjoc201807038
Abstract:
Compared with traditional chemical catalysis or enzymatic synthesis, chemoenzymatic relay reaction is a simpler, more efficient and economical method. It not only has the advantages of high efficiency and selectivity of enzyme catalysis, but also has the advantages of low price of synthetic raw materials, simple and high efficiency of synthetic process, green and friendly production environment, and excellent optical purity of the obtained product. Thus, chemoenzymatic relay synthesis methods have been widely used in the synthesis of high-value chiral compounds. In recent years, chemists have been committed to making chemoenzymatic catalytic conditions easier by changing catalysts and designing more reasonable ways, which could be used in more fields. In this review, the recent progress in the synthesis of chiral alcohols, epoxides, heterocyclics and other chiral compounds by using chemoenzymatic relay synthesis, such as enzyme and metal catalysis, enzyme and organic catalysis, enzyme and new reaction techniques, is reviewed, and the development trends of this field are also prospected.
Compared with traditional chemical catalysis or enzymatic synthesis, chemoenzymatic relay reaction is a simpler, more efficient and economical method. It not only has the advantages of high efficiency and selectivity of enzyme catalysis, but also has the advantages of low price of synthetic raw materials, simple and high efficiency of synthetic process, green and friendly production environment, and excellent optical purity of the obtained product. Thus, chemoenzymatic relay synthesis methods have been widely used in the synthesis of high-value chiral compounds. In recent years, chemists have been committed to making chemoenzymatic catalytic conditions easier by changing catalysts and designing more reasonable ways, which could be used in more fields. In this review, the recent progress in the synthesis of chiral alcohols, epoxides, heterocyclics and other chiral compounds by using chemoenzymatic relay synthesis, such as enzyme and metal catalysis, enzyme and organic catalysis, enzyme and new reaction techniques, is reviewed, and the development trends of this field are also prospected.
2019, 39(3): 679-696
doi: 10.6023/cjoc201807007
Abstract:
The impending global energy crisis and inefficient energy utilization have driven the use of energy efficient devices for display and lighting applications. Energy-efficient organic light emitting diodes (OLEDs) are considered to be the next generation of smart displays, becoming one of the most competitive candidate for future energy-efficient lighting sources. The molecular design of high-efficiency deep blue materials are greatly limited due to their inherent wide bandgap, poor carrier charge balance and their low efficiency in the solid state. As a novel building block for blue-emitting materials, phenanthroimidazole (PI) group is attractive stems from their bipolar feature and excellent fluorescence efficiency, which has aroused strong interest of researchers. Molecular design and photophysical properties of phenanthroimidazole-based deep blue-emitting materials are of great significance. In this review, an overview of the recent studies on PI-based blue emitters for applications in organic light-emitting diodes (OLEDs) is presented. The luminescence mechanism, design and latest developments of the electroluminescent devices fabricated from phenanthroimidazole derivatives are described, and their prospects in the future of full-color display and solid-state lighting are forecasted.
The impending global energy crisis and inefficient energy utilization have driven the use of energy efficient devices for display and lighting applications. Energy-efficient organic light emitting diodes (OLEDs) are considered to be the next generation of smart displays, becoming one of the most competitive candidate for future energy-efficient lighting sources. The molecular design of high-efficiency deep blue materials are greatly limited due to their inherent wide bandgap, poor carrier charge balance and their low efficiency in the solid state. As a novel building block for blue-emitting materials, phenanthroimidazole (PI) group is attractive stems from their bipolar feature and excellent fluorescence efficiency, which has aroused strong interest of researchers. Molecular design and photophysical properties of phenanthroimidazole-based deep blue-emitting materials are of great significance. In this review, an overview of the recent studies on PI-based blue emitters for applications in organic light-emitting diodes (OLEDs) is presented. The luminescence mechanism, design and latest developments of the electroluminescent devices fabricated from phenanthroimidazole derivatives are described, and their prospects in the future of full-color display and solid-state lighting are forecasted.
2019, 39(3): 697-702
doi: 10.6023/cjoc201808035
Abstract:
A 3-hydroxyflavonoid esters HFBA was synthesized by the reaction of 2-hydroxyacetophenone with p-methyl benzaldehyde, and its structure was characterized by NMR and high resolution mass spectrometer. The recognition behaviors of HFBA to hydrazine were investigated and the results show that HFBA exhibits good selectivity and sensitivity to N2H4 with fast response and good anti-interference ability in DMSO/PBS buffer (pH=7.4). Furthermore, the detection limit of HFBA for hydrazine was estimated to be 0.11 μmol/L, and the probe HFBA was successfully applied for the imaging of hydrazine in living cells.
A 3-hydroxyflavonoid esters HFBA was synthesized by the reaction of 2-hydroxyacetophenone with p-methyl benzaldehyde, and its structure was characterized by NMR and high resolution mass spectrometer. The recognition behaviors of HFBA to hydrazine were investigated and the results show that HFBA exhibits good selectivity and sensitivity to N2H4 with fast response and good anti-interference ability in DMSO/PBS buffer (pH=7.4). Furthermore, the detection limit of HFBA for hydrazine was estimated to be 0.11 μmol/L, and the probe HFBA was successfully applied for the imaging of hydrazine in living cells.
2019, 39(3): 709-719
doi: 10.6023/cjoc201808045
Abstract:
o-Quinone derivatives are not only a variety of active and important intermediate, but also widely used in the synthesis of natural products and medicinal chemistry. In the present study, the Sc(Ⅲ) catalyzed aza-Michael addition to o-quinone methides by amines for the synthesis of Betti base derivatives was developed. The reaction was performed in a sealed tube at 90℃ for 4 h and the products were obtained in moderate to good yields (76%~96%).
o-Quinone derivatives are not only a variety of active and important intermediate, but also widely used in the synthesis of natural products and medicinal chemistry. In the present study, the Sc(Ⅲ) catalyzed aza-Michael addition to o-quinone methides by amines for the synthesis of Betti base derivatives was developed. The reaction was performed in a sealed tube at 90℃ for 4 h and the products were obtained in moderate to good yields (76%~96%).
2019, 39(3): 720-726
doi: 10.6023/cjoc201810001
Abstract:
Owing to the unique macrocyclic-cavity structure of crown ether and the capability of complexing with guest molecules, our group successfully designed and synthesized a novel Sailboat-Shaped self-complex by using intramolecular hydrogen bonds, which are able to switch its configuration during the different pH value. Furthermore, a novel catenane which based on the sailboat-shaped self-complex was obtained by using intermolecular charge transfer interaction and through the template-directed method, and its structure was identified by 1H NMR, 13C NMR, HRMS and 1H-1H NOESY. It is hoped that it can be successfully controlled by the pH value conversion.
Owing to the unique macrocyclic-cavity structure of crown ether and the capability of complexing with guest molecules, our group successfully designed and synthesized a novel Sailboat-Shaped self-complex by using intramolecular hydrogen bonds, which are able to switch its configuration during the different pH value. Furthermore, a novel catenane which based on the sailboat-shaped self-complex was obtained by using intermolecular charge transfer interaction and through the template-directed method, and its structure was identified by 1H NMR, 13C NMR, HRMS and 1H-1H NOESY. It is hoped that it can be successfully controlled by the pH value conversion.
2019, 39(3): 754-760
doi: 10.6023/cjoc201808027
Abstract:
The complex of[Rh(COD) Cl]2 and 2R, 4R) -(+) -2, 4-bis(diphenylphosphino) pentane was used as an effective catalyst for the asymmetric ring opening reaction of oxabenzonorbornadienes with various phenols by employing ZnI2 as the activator. Under the optimized reaction conditions, high enantioselectivities with good yields could be obtained from a wide scope of oxabenzonorbornadienes and phenols.
The complex of[Rh(COD) Cl]2 and 2R, 4R) -(+) -2, 4-bis(diphenylphosphino) pentane was used as an effective catalyst for the asymmetric ring opening reaction of oxabenzonorbornadienes with various phenols by employing ZnI2 as the activator. Under the optimized reaction conditions, high enantioselectivities with good yields could be obtained from a wide scope of oxabenzonorbornadienes and phenols.
2019, 39(3): 771-777
doi: 10.6023/cjoc201807043
Abstract:
The benzothiazin-4-one intermediates were prepared by the one-pot three-components condensation from the N-Boc-L-prolinal 1, amino acid ethyl/methyl ester hydrochlorides 2a~2d, and mercaptobenzoic acids 3a~3b. After removal of Boc, the target novel fused tetracyclic thiazinan-4-one derivatives 6~11 were afforded by the intramolecular cyclo-amidation reaction. The absolute configurations of the newly generated chiral carbon (1-C) were determined by the coupling constants of H-1 and H-2 and the X-ray crystallographic structures. The tetracyclic alkaloids were examined for their anti-proliferative activity against Hela and A549 tumor cells. The results showed that some compounds could moderately inhibit the growth of Hela cells, and among them, (13aR, 13bR) -1, 2, 3, 13b-tetrahydrobenzo[e]pyrrolo[2', 1':3, 4]pyrazino[2, 1-b][1, 3]thiazine-5, 8(6H, 13aH) -dione (6b) was the best one with the IC50 value of 9.50 μmol/L. However, all the compounds showed no anti-tumor activity against A549.
The benzothiazin-4-one intermediates were prepared by the one-pot three-components condensation from the N-Boc-L-prolinal 1, amino acid ethyl/methyl ester hydrochlorides 2a~2d, and mercaptobenzoic acids 3a~3b. After removal of Boc, the target novel fused tetracyclic thiazinan-4-one derivatives 6~11 were afforded by the intramolecular cyclo-amidation reaction. The absolute configurations of the newly generated chiral carbon (1-C) were determined by the coupling constants of H-1 and H-2 and the X-ray crystallographic structures. The tetracyclic alkaloids were examined for their anti-proliferative activity against Hela and A549 tumor cells. The results showed that some compounds could moderately inhibit the growth of Hela cells, and among them, (13aR, 13bR) -1, 2, 3, 13b-tetrahydrobenzo[e]pyrrolo[2', 1':3, 4]pyrazino[2, 1-b][1, 3]thiazine-5, 8(6H, 13aH) -dione (6b) was the best one with the IC50 value of 9.50 μmol/L. However, all the compounds showed no anti-tumor activity against A549.
2019, 39(3): 786-792
doi: 10.6023/cjoc201807053
Abstract:
NS5 is a protein component which plays a main role in replication of Zika virus, and its component part-methyl-transferase (5M5B) is the central participants of virus replication and host innate immune response. So it is used as the preferred protein of potential antiviral drugs development. Using 5M5B as receptors and using its binding sites to screen with over 2 million small molecule compounds, the leading compounds of anti-Zika virus were obtained. The structural optimization, activity prediction, chemical synthesis and pharmacological activity of the leading compound were studied. All the synthesized compounds were characterized by 1H NMR and 13C NMR. The antiviral activity of compound 3a is better than that of ribavirin (IC50=(7.69±0.36) μmol·L-1 for 3a vs IC50=(8.15±0.42) μmol·L-1 for ribavirin).
NS5 is a protein component which plays a main role in replication of Zika virus, and its component part-methyl-transferase (5M5B) is the central participants of virus replication and host innate immune response. So it is used as the preferred protein of potential antiviral drugs development. Using 5M5B as receptors and using its binding sites to screen with over 2 million small molecule compounds, the leading compounds of anti-Zika virus were obtained. The structural optimization, activity prediction, chemical synthesis and pharmacological activity of the leading compound were studied. All the synthesized compounds were characterized by 1H NMR and 13C NMR. The antiviral activity of compound 3a is better than that of ribavirin (IC50=(7.69±0.36) μmol·L-1 for 3a vs IC50=(8.15±0.42) μmol·L-1 for ribavirin).
2019, 39(3): 793-799
doi: 10.6023/cjoc201807036
Abstract:
A series of red fluorescent dyes were synthesized using 3-N, N-diethylaminophenol. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS. The optical properties of these dyes were detected. Bovine serum albumin was labeled by new dyes. The fluorescence signal values of these dyes and cyanine-3 (Cy3) in lectin microarrays were compared. The results show that the maximum emission wavelengths of these dyes are above 600 nm and the Stokes shifts are about 70 nm. The dye/protein (D/P) labeling efficiencies of these dyes are as high as 1.5~1.8. The fluorescence signal of new dyes is equal to Cy3 in lectin microarray. Hence, these dyes can also be used as fluorescent labels for detection of sugar chain changes in lectin microarrays.
A series of red fluorescent dyes were synthesized using 3-N, N-diethylaminophenol. Their structures were characterized by 1H NMR, 13C NMR, IR and HRMS. The optical properties of these dyes were detected. Bovine serum albumin was labeled by new dyes. The fluorescence signal values of these dyes and cyanine-3 (Cy3) in lectin microarrays were compared. The results show that the maximum emission wavelengths of these dyes are above 600 nm and the Stokes shifts are about 70 nm. The dye/protein (D/P) labeling efficiencies of these dyes are as high as 1.5~1.8. The fluorescence signal of new dyes is equal to Cy3 in lectin microarray. Hence, these dyes can also be used as fluorescent labels for detection of sugar chain changes in lectin microarrays.
2019, 39(3): 703-708
doi: 10.6023/cjoc201808037
Abstract:
Three series of chalcones bearing a piperidino, morpholino, and 1-methylpiperazino moiety were synthesized in two steps with the key step being Claisen-Schmidt condensation and tested for the activity against five cell lines, MCF-7 (human breast adenocarcinoma cell line), A549 (human lung adenocarcinoma epithelial cell line), HL-60 (human leukemia cell line), Hela (human cervical cancer cell line), and Bewo (human chorionic tumor cell line) by thiazolyl blue tetrazolium bromide (MTT) assay. Some chalcones exhibited good anticancer activity, and among them 4a, 4e, 4f, 4j, 4m, and 4o displayed the best anticancer activity for MCF-7 breast cancer cells, A549 lung cancer cells, and HL-60 leukemia cancer cells with IC50 values below 10 μmol/L, respectively.
Three series of chalcones bearing a piperidino, morpholino, and 1-methylpiperazino moiety were synthesized in two steps with the key step being Claisen-Schmidt condensation and tested for the activity against five cell lines, MCF-7 (human breast adenocarcinoma cell line), A549 (human lung adenocarcinoma epithelial cell line), HL-60 (human leukemia cell line), Hela (human cervical cancer cell line), and Bewo (human chorionic tumor cell line) by thiazolyl blue tetrazolium bromide (MTT) assay. Some chalcones exhibited good anticancer activity, and among them 4a, 4e, 4f, 4j, 4m, and 4o displayed the best anticancer activity for MCF-7 breast cancer cells, A549 lung cancer cells, and HL-60 leukemia cancer cells with IC50 values below 10 μmol/L, respectively.
2019, 39(3): 727-733
doi: 10.6023/cjoc201810003
Abstract:
α, α-Dibromomethyl ketones were synthesized with high yields through a thiophenol-promoted reduction of α, α, α-tribromomethyl ketones under mild conditions within one hour. A further mechanistic study showed that the reaction proceeded via a radical process. This is an example that uses thiophenol as the radical stimulator in the reduction of multi-halogenated compounds.
α, α-Dibromomethyl ketones were synthesized with high yields through a thiophenol-promoted reduction of α, α, α-tribromomethyl ketones under mild conditions within one hour. A further mechanistic study showed that the reaction proceeded via a radical process. This is an example that uses thiophenol as the radical stimulator in the reduction of multi-halogenated compounds.
2019, 39(3): 734-746
doi: 10.6023/cjoc201809027
Abstract:
Nano-gold catalyzed transesterification of the (hetero) aryl ester with alkyl halides via C-O activation has been developed. In a series of supported AuNPs and PdNPs, the Au/γ-Al2O3 catalyst with an AuNP mean diameter of 3.63 nm and 3 wt% Au loading exhibited the best catalytic performance. The catalyst can be reused and shows high activity after five cycles. The X-ray photoelectron spectroscopy (XPS) analysis of the catalyst before and after the reaction suggested that the reaction might be performed via a catalytic cycle that began with Au0.
Nano-gold catalyzed transesterification of the (hetero) aryl ester with alkyl halides via C-O activation has been developed. In a series of supported AuNPs and PdNPs, the Au/γ-Al2O3 catalyst with an AuNP mean diameter of 3.63 nm and 3 wt% Au loading exhibited the best catalytic performance. The catalyst can be reused and shows high activity after five cycles. The X-ray photoelectron spectroscopy (XPS) analysis of the catalyst before and after the reaction suggested that the reaction might be performed via a catalytic cycle that began with Au0.
2019, 39(3): 747-753
doi: 10.6023/cjoc201808022
Abstract:
Spiroacetal motif is widely distributed in many bioactive natural products of different origins and essentially contributes to various bioactivities. In this paper, two series of spiroacetals were synthesized and biologically evaluated as insect sex attractant towards oriental fruit flies (Bactrocera dorsalis) using methyleugenol as the standard. Biological evaluation demonstrated that a large part of the tested compounds triggered apparent electrophysiological responses from both male and female fruit flies. The stereochemistry of the spiroacetals and the substitution on their phenyl rings influenced the responses to some degree.
Spiroacetal motif is widely distributed in many bioactive natural products of different origins and essentially contributes to various bioactivities. In this paper, two series of spiroacetals were synthesized and biologically evaluated as insect sex attractant towards oriental fruit flies (Bactrocera dorsalis) using methyleugenol as the standard. Biological evaluation demonstrated that a large part of the tested compounds triggered apparent electrophysiological responses from both male and female fruit flies. The stereochemistry of the spiroacetals and the substitution on their phenyl rings influenced the responses to some degree.
2019, 39(3): 761-770
doi: 10.6023/cjoc201806017
Abstract:
Three new bipolar derivatives based on 2, 4, 6-triphenyl-1, 3, 5-triazine and fluorene moieties, namely FTRZ, pTFTRZ and mTFTRZ were designed and synthesized by using 9-(4-(hexyloxy) phenyl) -9H-fluorene, 2-bromo-4, 6-diphenyl-1, 3, 5-triazine, 2, 4, 6-tris(4-bromophenyl) -1, 3, 5-triazine, and 2, 4, 6-tris(3-bromophenyl) -1, 3, 5-triazine through palladium-cata-lyzed cross-coupling reaction, which were reported as hosts for thermally activated delayed fluorescence organic light-emitting diodes (OLEDs). The 1H NMR, 13C NMR and MALDI-TOF-MS spectra were used to characterize the chemical structure of compounds FTRZ, pTFTRZ and mTFTRZ. Their thermal, photophysical and electrochemical properties as well as electroluminescent device performance were thoroughly investigated to correlate the optoelectronic properties with the topology-varied molecular structure. The thermal decomposition temperatures of compounds FTRZ, pTFTRZ and mTFTRZ are 427, 446 and 424℃ and their glass transition temperatures of compounds pFTRZ and mTFTRZ are 120 and 103℃, respectively. The optical band gaps of compounds FTRZ, pTFTRZ and mTFTRZ in toluene solution are 3.24, 3.29 and 3.24 eV, and their triplet energy levels are 3.04, 3.11 and 3.05 eV, respectively. Due to the π-π interaction between 2, 4, 6-triphenyl-1, 3, 5-triazine planes, compounds FTRZ, pTFTRZ and mTFTRZ form excimer in the thin film state. The electroluminescent properties of OLEDs using compounds FTRZ, pTFTRZ and mTFTRZ as the hosts and 2, 4, 5, 6-tetrakis(carbazol-9-yl) -1, 3-dicyanobenzene as the guest emitter were investigated. The green OLED of compound FTRZ as host material shows a peak emission at 510 nm with a maximum current efficiency of 6.7 cd/A, a maximum external quantum efficiency of 2.07% and a maximum brightness of 35718 cd/m2. The efficiency roll-offs of the OLEDs hosted by compounds FTRZ and pTFTRZ at 20000 cd/m2 are 3% and 2%, which are much better than the same device hosted by compound mTFTRZ.
Three new bipolar derivatives based on 2, 4, 6-triphenyl-1, 3, 5-triazine and fluorene moieties, namely FTRZ, pTFTRZ and mTFTRZ were designed and synthesized by using 9-(4-(hexyloxy) phenyl) -9H-fluorene, 2-bromo-4, 6-diphenyl-1, 3, 5-triazine, 2, 4, 6-tris(4-bromophenyl) -1, 3, 5-triazine, and 2, 4, 6-tris(3-bromophenyl) -1, 3, 5-triazine through palladium-cata-lyzed cross-coupling reaction, which were reported as hosts for thermally activated delayed fluorescence organic light-emitting diodes (OLEDs). The 1H NMR, 13C NMR and MALDI-TOF-MS spectra were used to characterize the chemical structure of compounds FTRZ, pTFTRZ and mTFTRZ. Their thermal, photophysical and electrochemical properties as well as electroluminescent device performance were thoroughly investigated to correlate the optoelectronic properties with the topology-varied molecular structure. The thermal decomposition temperatures of compounds FTRZ, pTFTRZ and mTFTRZ are 427, 446 and 424℃ and their glass transition temperatures of compounds pFTRZ and mTFTRZ are 120 and 103℃, respectively. The optical band gaps of compounds FTRZ, pTFTRZ and mTFTRZ in toluene solution are 3.24, 3.29 and 3.24 eV, and their triplet energy levels are 3.04, 3.11 and 3.05 eV, respectively. Due to the π-π interaction between 2, 4, 6-triphenyl-1, 3, 5-triazine planes, compounds FTRZ, pTFTRZ and mTFTRZ form excimer in the thin film state. The electroluminescent properties of OLEDs using compounds FTRZ, pTFTRZ and mTFTRZ as the hosts and 2, 4, 5, 6-tetrakis(carbazol-9-yl) -1, 3-dicyanobenzene as the guest emitter were investigated. The green OLED of compound FTRZ as host material shows a peak emission at 510 nm with a maximum current efficiency of 6.7 cd/A, a maximum external quantum efficiency of 2.07% and a maximum brightness of 35718 cd/m2. The efficiency roll-offs of the OLEDs hosted by compounds FTRZ and pTFTRZ at 20000 cd/m2 are 3% and 2%, which are much better than the same device hosted by compound mTFTRZ.
2019, 39(3): 778-785
doi: 10.6023/cjoc201808005
Abstract:
Magnetic resonance imaging (MRI) is widely used in diagnostic medicine and soft tissue imaging. Contrast agents (CAs) can improve the specificity of MRI enhancement. Herein, the design, synthesis and characterization of twelve novel Gd-based 1, 4, 7, 10-tetraazacyclododecan-N, N', N, N'-tetraacetic acid (DOTA) -hydrazide derived contrast agents for MRI were reported. Among of them, 5d, 5h and 5l exhibit higher longitudinal relaxivities than the clinical Gd-DOTA at 0.5 T. The relaxivities r1 of 5d, 5h and 5l are 4.67, 4.85 and 5.33 L·mmol-1·s-1 respectively. In vivo liver-target MRI shows that the potential of complex 5d was used as a novel liver-target contrast agent for MRI.
Magnetic resonance imaging (MRI) is widely used in diagnostic medicine and soft tissue imaging. Contrast agents (CAs) can improve the specificity of MRI enhancement. Herein, the design, synthesis and characterization of twelve novel Gd-based 1, 4, 7, 10-tetraazacyclododecan-N, N', N, N'-tetraacetic acid (DOTA) -hydrazide derived contrast agents for MRI were reported. Among of them, 5d, 5h and 5l exhibit higher longitudinal relaxivities than the clinical Gd-DOTA at 0.5 T. The relaxivities r1 of 5d, 5h and 5l are 4.67, 4.85 and 5.33 L·mmol-1·s-1 respectively. In vivo liver-target MRI shows that the potential of complex 5d was used as a novel liver-target contrast agent for MRI.
2019, 39(3): 800-810
doi: 10.6023/cjoc201808003
Abstract:
Lewis acid La(OTf) 3-catalyzed chemoselective cyclization of hydroxyl substituted ethylenediamine derivatives with aldehydes has been described for the first time, which provides efficient access to diversely functionalized 1, 3-imidazoli-dines and 3, 1-benzoxazines in generally good yields only by adjusting the position of the methylene group within hydroxyl substituted ethylenediamines. The reaction is suitable to aromatic aldehydes and aliphatic ones. Plausible mechanisms are also proposed to explain the observed reaction modes, wherein the nucleophilicity of nitrogen and oxygen atoms plays an important role in controlling the chemoselectivity.
Lewis acid La(OTf) 3-catalyzed chemoselective cyclization of hydroxyl substituted ethylenediamine derivatives with aldehydes has been described for the first time, which provides efficient access to diversely functionalized 1, 3-imidazoli-dines and 3, 1-benzoxazines in generally good yields only by adjusting the position of the methylene group within hydroxyl substituted ethylenediamines. The reaction is suitable to aromatic aldehydes and aliphatic ones. Plausible mechanisms are also proposed to explain the observed reaction modes, wherein the nucleophilicity of nitrogen and oxygen atoms plays an important role in controlling the chemoselectivity.
2019, 39(3): 811-820
doi: 10.6023/cjoc201807011
Abstract:
A catalytic system for the oxidation of benzylic ethers to esters has been developed utilizing reusable MnOx-N@C as catalyst and tert-butyl hydroperoxide (TBHP) as benign oxidant under neat condition. The catalytic oxidation system has good functional groups tolerance and excellent chemoselectivity, and this catalytic procedure can also be scaled up.
A catalytic system for the oxidation of benzylic ethers to esters has been developed utilizing reusable MnOx-N@C as catalyst and tert-butyl hydroperoxide (TBHP) as benign oxidant under neat condition. The catalytic oxidation system has good functional groups tolerance and excellent chemoselectivity, and this catalytic procedure can also be scaled up.
2019, 39(3): 821-829
doi: 10.6023/cjoc201807022
Abstract:
In this work, twelve dihydropyrimidinethione derivatives have been synthesized from isolongifolanone by aldol and cyclization reactions. The chemical structures were characterized by 1H NMR, 13C NMR and high resolution mass spectrometry (HRMS), and the structure of compound 3e was determined by X-ray single crystal diffraction. Their in vitro cytotoxicity against three cancer cell lines breast (MDA-MB-231), cervix (HeLa), liver (HepG-2) and one normal cell line mouse macrophages (Raw-264.7) were investigated. It was shown that these 12 compounds had good antitumor activity with IC50 values of 3.12~44.28 μmol/L. Among them, compounds 3j, 3g, and 3k had the best antitumor activity against MDA-MB-231 cells (IC50=3.12 μmol/L), HeLa cells (IC50=4.04 μmol/L) and HepG-2 cells (IC50=5.43 μmol/L), respectively. In addition, compound 3j arrested the cells in the G0/G1 phase of the MDA-MB-231 cell cycle and induced the early apoptosis of MDA-MB-231 cells in a dose-dependent manner.
In this work, twelve dihydropyrimidinethione derivatives have been synthesized from isolongifolanone by aldol and cyclization reactions. The chemical structures were characterized by 1H NMR, 13C NMR and high resolution mass spectrometry (HRMS), and the structure of compound 3e was determined by X-ray single crystal diffraction. Their in vitro cytotoxicity against three cancer cell lines breast (MDA-MB-231), cervix (HeLa), liver (HepG-2) and one normal cell line mouse macrophages (Raw-264.7) were investigated. It was shown that these 12 compounds had good antitumor activity with IC50 values of 3.12~44.28 μmol/L. Among them, compounds 3j, 3g, and 3k had the best antitumor activity against MDA-MB-231 cells (IC50=3.12 μmol/L), HeLa cells (IC50=4.04 μmol/L) and HepG-2 cells (IC50=5.43 μmol/L), respectively. In addition, compound 3j arrested the cells in the G0/G1 phase of the MDA-MB-231 cell cycle and induced the early apoptosis of MDA-MB-231 cells in a dose-dependent manner.
2019, 39(3): 830-835
doi: 10.6023/cjoc201812051
Abstract:
A dehydrative cross coupling of ketone-stabilized phosphorus ylides with the readily available allylic alcohols followed by an one-pot Wittig reaction is developed. A range of functional 1, 4-dienes could be obtained in 52%~95% isolated yields in the presence of 5 mol% Pd(PPh3) 4 and 20 mol% B(OH) 3. The same method can be extended to ester or nitrile-stabi-lized phosphorus ylides, affording the corresponding 1, 4-dienes in moderate yields.
A dehydrative cross coupling of ketone-stabilized phosphorus ylides with the readily available allylic alcohols followed by an one-pot Wittig reaction is developed. A range of functional 1, 4-dienes could be obtained in 52%~95% isolated yields in the presence of 5 mol% Pd(PPh3) 4 and 20 mol% B(OH) 3. The same method can be extended to ester or nitrile-stabi-lized phosphorus ylides, affording the corresponding 1, 4-dienes in moderate yields.
2019, 39(3): 836-841
doi: 10.6023/cjoc201809009
Abstract:
Twelve new piperdine thiazole compounds were designed and synthesized in search of new bioactive compounds. The preliminary bioassay showed that at the concentration of 500 μg/mL the lethal rates of the target compounds possessed certain insceticidal activities against armyworm, and at the concentration of 100 μg/mL the lethal rates of (4-(5-(3-chloro-phenyl) -4-methylthiazol-2-yl) piperidin-1-yl) (4-methylpiperazin-1-yl) methanone (1f) and (4-(5-(4-chlorophenyl) -4-methyl-thiazol-2-yl) piperidin-1-yl) nitro-1H-pyrazol-3-yl) methanone (1g) against armyworm were 80% and 100%, respectively. Further screening at concentrations of 20 μg/mL, the lethal rate of (4-(5-(4-chlorophenyl) -4-methylthiazol-2-yl) piperidin-1-yl) (4-nitro-1H-pyrazol-3-yl) methanone (1g) against armyworm was 50%.
Twelve new piperdine thiazole compounds were designed and synthesized in search of new bioactive compounds. The preliminary bioassay showed that at the concentration of 500 μg/mL the lethal rates of the target compounds possessed certain insceticidal activities against armyworm, and at the concentration of 100 μg/mL the lethal rates of (4-(5-(3-chloro-phenyl) -4-methylthiazol-2-yl) piperidin-1-yl) (4-methylpiperazin-1-yl) methanone (1f) and (4-(5-(4-chlorophenyl) -4-methyl-thiazol-2-yl) piperidin-1-yl) nitro-1H-pyrazol-3-yl) methanone (1g) against armyworm were 80% and 100%, respectively. Further screening at concentrations of 20 μg/mL, the lethal rate of (4-(5-(4-chlorophenyl) -4-methylthiazol-2-yl) piperidin-1-yl) (4-nitro-1H-pyrazol-3-yl) methanone (1g) against armyworm was 50%.
2019, 39(3): 842-847
doi: 10.6023/cjoc201809019
Abstract:
Three new isosteroidal alkaloids, karelinine (1), 5-epikarelinine (2), and 27-epiebeienine (3), were isolated from the bulbs of Fritillaria karelinii by column chromatography and semipreparative HPLC (high performance liquid chro-matography), together with three known ones, ebeienine (4), persicanidine B (5), and heilonine (6). Their structures were identified by MS, 1D/2D NMR, and single-crystal X-ray diffraction. Compound 1 is a 5β-jervine isosteroidal alkaloid featuring a cis-fused A/B ring moiety, rarely found in the Fritillaria genus. Compounds 1 and 2 also represent the first jervine alkaloids with a 15 α-hydroxy group from this genus.
Three new isosteroidal alkaloids, karelinine (1), 5-epikarelinine (2), and 27-epiebeienine (3), were isolated from the bulbs of Fritillaria karelinii by column chromatography and semipreparative HPLC (high performance liquid chro-matography), together with three known ones, ebeienine (4), persicanidine B (5), and heilonine (6). Their structures were identified by MS, 1D/2D NMR, and single-crystal X-ray diffraction. Compound 1 is a 5β-jervine isosteroidal alkaloid featuring a cis-fused A/B ring moiety, rarely found in the Fritillaria genus. Compounds 1 and 2 also represent the first jervine alkaloids with a 15 α-hydroxy group from this genus.
2019, 39(3): 848-851
doi: 10.6023/cjoc201807059
Abstract:
Three new polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from Hypericum lagarocladum by means of various chromatographic techniques. Their structures were identified as hyperlagarin A (1), hyperlagarin B (2), and hyperlagarin C (3) on the basis of extensive spectroscopic analyses, including HRMS, 1D-and 2D-NMR.
Three new polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from Hypericum lagarocladum by means of various chromatographic techniques. Their structures were identified as hyperlagarin A (1), hyperlagarin B (2), and hyperlagarin C (3) on the basis of extensive spectroscopic analyses, including HRMS, 1D-and 2D-NMR.
2019, 39(3): 852-860
doi: 10.6023/cjoc201807044
Abstract:
A series of novel 4-arylamino pyrimidine derivatives were synthesized using substituted aniline as starting material via diazotization, Meerwein arylation, isothiocyanation, addition, methylation and cyclization. The preliminary results of insecticidal activities indicated that most of the compounds exhibited 100% insecticidal activitiy against Mythimna separata Walker at 500 mg/L. At 20 mg/L, N-(2-chloro-4-fluorophenyl) -2, 6-dimethyl-5-(4-phenoxy-2-(trifluoromethyl) phenyl) -pyrimidin-4-amine (6h) exhibited 80% and 60% mortality against Mythimna separata Walker and Plutella xylostella Linnaeus, respectively.
A series of novel 4-arylamino pyrimidine derivatives were synthesized using substituted aniline as starting material via diazotization, Meerwein arylation, isothiocyanation, addition, methylation and cyclization. The preliminary results of insecticidal activities indicated that most of the compounds exhibited 100% insecticidal activitiy against Mythimna separata Walker at 500 mg/L. At 20 mg/L, N-(2-chloro-4-fluorophenyl) -2, 6-dimethyl-5-(4-phenoxy-2-(trifluoromethyl) phenyl) -pyrimidin-4-amine (6h) exhibited 80% and 60% mortality against Mythimna separata Walker and Plutella xylostella Linnaeus, respectively.
2019, 39(3): 861-866
doi: 10.6023/cjoc201808033
Abstract:
A series of 3-(((3-bromo-1-(3-chloropyridin-2-yl) -1H-pyrazol-5-yl) methylene) amino) substituted-benzo[d][1, 2, 3]-triazin-4(3H) -ones were synthesized successfully with ethyl N-pyridylpyrazole carboxylate and substituted aminobenzoic acids as starting materials, via multi-step reactions of reduction, oxidation, nucleophilic addition, condensation and diazotization. The preliminary bioassay tests indicated that most of these compounds have certain insecticidal activities, among which one compound showed a mortality rate of 70% towards Mythimna separata Walker at the test concentration of 200 mg·L-1, some compounds exhibited favorable fungicidal activities at 50 mg·L-1, particularly two compounds which possessed 92.3% growth inhibitory rate against Physalospora piricola, could be used as new fungicidal leading structures for further investigations on this type of compounds.
A series of 3-(((3-bromo-1-(3-chloropyridin-2-yl) -1H-pyrazol-5-yl) methylene) amino) substituted-benzo[d][1, 2, 3]-triazin-4(3H) -ones were synthesized successfully with ethyl N-pyridylpyrazole carboxylate and substituted aminobenzoic acids as starting materials, via multi-step reactions of reduction, oxidation, nucleophilic addition, condensation and diazotization. The preliminary bioassay tests indicated that most of these compounds have certain insecticidal activities, among which one compound showed a mortality rate of 70% towards Mythimna separata Walker at the test concentration of 200 mg·L-1, some compounds exhibited favorable fungicidal activities at 50 mg·L-1, particularly two compounds which possessed 92.3% growth inhibitory rate against Physalospora piricola, could be used as new fungicidal leading structures for further investigations on this type of compounds.
2019, 39(3): 867-872
doi: 10.6023/cjoc201806029
Abstract:
In order to find lead compounds with high fungicidal activity, the phenyl moiety of pydiflumetofen was replaced by substituted 1-phenyl-3-hydroxylpyrazole moiety of pyraclostrobin according to the method of active substructure combination. 12 novel N-alkoxyl amides were synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS. Preliminary fungicidal activity screening results showed that some analogues exhibited certain fungicidal activity against Phakopsora pachyrhizi, Pseudoperonospora cubensis or Erysiphe cichoracearum, compound 3a displayed 95% protective effect against Erysiphe cichoracearum at 100 mg/L.
In order to find lead compounds with high fungicidal activity, the phenyl moiety of pydiflumetofen was replaced by substituted 1-phenyl-3-hydroxylpyrazole moiety of pyraclostrobin according to the method of active substructure combination. 12 novel N-alkoxyl amides were synthesized and their structures were confirmed by 1H NMR, 13C NMR and HRMS. Preliminary fungicidal activity screening results showed that some analogues exhibited certain fungicidal activity against Phakopsora pachyrhizi, Pseudoperonospora cubensis or Erysiphe cichoracearum, compound 3a displayed 95% protective effect against Erysiphe cichoracearum at 100 mg/L.
2019, 39(3): 873-877
doi: 10.6023/cjoc201808006
Abstract:
An efficient, solvent-free procedure using sodium as catalyst for the aminolysis of monoesters is reported. A detailed comparison of catalysts between sodium and sodium amide was made. It was found that the fresh sodium amide by in-situ synthesis of sodium with ammonia was more active than the indirectly adding sodium amide. As compared to the previously reported approaches, the procedure given in this work is much faster and performed under mild conditions. Furthermore, this procedure is applied successfully for the aminolysis of other monoesters.
An efficient, solvent-free procedure using sodium as catalyst for the aminolysis of monoesters is reported. A detailed comparison of catalysts between sodium and sodium amide was made. It was found that the fresh sodium amide by in-situ synthesis of sodium with ammonia was more active than the indirectly adding sodium amide. As compared to the previously reported approaches, the procedure given in this work is much faster and performed under mild conditions. Furthermore, this procedure is applied successfully for the aminolysis of other monoesters.
