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2016 Volume 36 Issue 3
2016, 36(3): 439-446
doi: 10.6023/cjoc201511054
Abstract:
Jiadifenolide, a new seco-prezizaane-type sesquiterpenoid, was isolated from Chinese unique medicine Illicium jiadifengpi. It contains a highly oxygenated cagelike architecture with seven contiguous stereocenters. It displays potent neurotrophic activity at very low concentration and is regarded as a promising lead compound for developing drugs for neurodegenerative diseases. This review summarizes the synthetic efforts towards jiadifenolide in the last five years.
Jiadifenolide, a new seco-prezizaane-type sesquiterpenoid, was isolated from Chinese unique medicine Illicium jiadifengpi. It contains a highly oxygenated cagelike architecture with seven contiguous stereocenters. It displays potent neurotrophic activity at very low concentration and is regarded as a promising lead compound for developing drugs for neurodegenerative diseases. This review summarizes the synthetic efforts towards jiadifenolide in the last five years.
2016, 36(3): 447-459
doi: 10.6023/cjoc201512009
Abstract:
Chiral alcohols are an important class of compounds and possess a broad array of applications, thus their asymmetric preparation is an important area of research in the field of organic synthesis. Amongst methodologies for the preparation of such compounds, catalytic asymmetric hydrogenation has gained widespread interest due to its efficiency, environmentally friendliness and economic advantages, and is gradually becoming a technology with great potential for the industrial preparation of chiral alcohols. This review provides the first overview for the catalytic asymmetric hydrogenation of enol esters for the synthesis of chiral alcohols. A comprehensive and up-to-date introduction are given for a number of different substrates. A thorough analysis is provided concerning the advantages and disadvantages of different chiral ligands and their transition-metal complexes. Finally, a brief discussion relating to developments and potential areas of further research concerning new substrates, new ligands and new catalytic metals, is presented.
Chiral alcohols are an important class of compounds and possess a broad array of applications, thus their asymmetric preparation is an important area of research in the field of organic synthesis. Amongst methodologies for the preparation of such compounds, catalytic asymmetric hydrogenation has gained widespread interest due to its efficiency, environmentally friendliness and economic advantages, and is gradually becoming a technology with great potential for the industrial preparation of chiral alcohols. This review provides the first overview for the catalytic asymmetric hydrogenation of enol esters for the synthesis of chiral alcohols. A comprehensive and up-to-date introduction are given for a number of different substrates. A thorough analysis is provided concerning the advantages and disadvantages of different chiral ligands and their transition-metal complexes. Finally, a brief discussion relating to developments and potential areas of further research concerning new substrates, new ligands and new catalytic metals, is presented.
2016, 36(3): 460-479
doi: 10.6023/cjoc201511026
Abstract:
Significant progress has been made in polymeric semiconductors and their organic field-effect transistors (OFETs) since 1980s. To date, hundreds of polymeric semiconductors have been reported and used for OFETs. The hole mobility above 36.3 cm2·V-1·s-1 has been achieved, which can be competitive with organic small semiconductors and even amorphous silicon. In this review, the recent progress in high-mobility polymeric semiconductor materials has been summarized from the perspective of design, synthesis, and OFET devices performance. Moreover, the recent developments are systematically summarized and analyzed according to different types of polymeric semiconductors, including p-type, n-type, and ambipolar polymeric semiconductors. The analysis about the relationship among the molecular structure-aggregation structure-OFET devices performance may guide the rational molecule design in the polymeric semiconductor materials with excellently comprehensive performance in the future.
Significant progress has been made in polymeric semiconductors and their organic field-effect transistors (OFETs) since 1980s. To date, hundreds of polymeric semiconductors have been reported and used for OFETs. The hole mobility above 36.3 cm2·V-1·s-1 has been achieved, which can be competitive with organic small semiconductors and even amorphous silicon. In this review, the recent progress in high-mobility polymeric semiconductor materials has been summarized from the perspective of design, synthesis, and OFET devices performance. Moreover, the recent developments are systematically summarized and analyzed according to different types of polymeric semiconductors, including p-type, n-type, and ambipolar polymeric semiconductors. The analysis about the relationship among the molecular structure-aggregation structure-OFET devices performance may guide the rational molecule design in the polymeric semiconductor materials with excellently comprehensive performance in the future.
2016, 36(3): 480-489
doi: 10.6023/cjoc201508004
Abstract:
Since the definition of "green chemistry" was proposed in 1991, the green solvents have attracted considerable attention. In the two decades ago, ionic liquids grew up. However, as following the research, it was found that ionic liquids had some drawbacks. Nowadays, some new types of low-transition-temperature mixtures, i.e. deep-eutectic solvents (DES) are raised. Compared with the traditional ionic liquids, deep-eutectic solvents are greener, cheaper and more accessible. Furthermore, the preparation methods of deep-eutectic solvents are easy, and the components of them are biodegradable. In recent years, deep-eutectic solvents have been applied as green solvents in organic synthesis widely. In this review, the application of deep-eutectic solvents in cyclization reactions, replacement reactions, addition reactions, multicomponent reactions, enzyme catalytic reactions and other reactions in the last few years are briefly summarized, and the prospects of DESs are also discussed.
Since the definition of "green chemistry" was proposed in 1991, the green solvents have attracted considerable attention. In the two decades ago, ionic liquids grew up. However, as following the research, it was found that ionic liquids had some drawbacks. Nowadays, some new types of low-transition-temperature mixtures, i.e. deep-eutectic solvents (DES) are raised. Compared with the traditional ionic liquids, deep-eutectic solvents are greener, cheaper and more accessible. Furthermore, the preparation methods of deep-eutectic solvents are easy, and the components of them are biodegradable. In recent years, deep-eutectic solvents have been applied as green solvents in organic synthesis widely. In this review, the application of deep-eutectic solvents in cyclization reactions, replacement reactions, addition reactions, multicomponent reactions, enzyme catalytic reactions and other reactions in the last few years are briefly summarized, and the prospects of DESs are also discussed.
2016, 36(3): 490-501
doi: 10.6023/cjoc201510006
Abstract:
Sulfonyl-containing compounds comprise a substantial proportion in the therapeutic drugs. It is an important strategy to introduce sulfonyl group into the small molecules for structure-based medicinal chemistry, the application of sulfonyl group in drug design is reviewed in this paper. Structurally, sulfonyl group has similar properties in molecular size and charge distribution with carbonyl, carboxyl, tetrazolium and phosphate group, so it can be introduced into the drug molecules as their bioisostere in order to remain or improve activity. Sulfonyl group possesses unique physicochemical properties, and the introduction of sulfonyl group can also modulate the solubility and acid-base property of the drug molecules. Sulfonyl group can offer two hydrogen-bond receptors, and reasonable introduction of sulfonyl group can enhance the binding affinity of the drug molecules with the targeted proteins to improve activity through hydrogen bond interactions. What's more, sulfonyl group is relatively stable in terms of structure, the introduction of sulfonyl group can increase the metabolic stability of drugs to prolong the duration of action by blocking metabolically labile sites, improve the pharmacokinetic properties of the drug molecules to elevate the bioavailability. Sulfonyl group belongs to polar groups, which can also increase the polarity of the drug molecules to diminish hERG activity.
Sulfonyl-containing compounds comprise a substantial proportion in the therapeutic drugs. It is an important strategy to introduce sulfonyl group into the small molecules for structure-based medicinal chemistry, the application of sulfonyl group in drug design is reviewed in this paper. Structurally, sulfonyl group has similar properties in molecular size and charge distribution with carbonyl, carboxyl, tetrazolium and phosphate group, so it can be introduced into the drug molecules as their bioisostere in order to remain or improve activity. Sulfonyl group possesses unique physicochemical properties, and the introduction of sulfonyl group can also modulate the solubility and acid-base property of the drug molecules. Sulfonyl group can offer two hydrogen-bond receptors, and reasonable introduction of sulfonyl group can enhance the binding affinity of the drug molecules with the targeted proteins to improve activity through hydrogen bond interactions. What's more, sulfonyl group is relatively stable in terms of structure, the introduction of sulfonyl group can increase the metabolic stability of drugs to prolong the duration of action by blocking metabolically labile sites, improve the pharmacokinetic properties of the drug molecules to elevate the bioavailability. Sulfonyl group belongs to polar groups, which can also increase the polarity of the drug molecules to diminish hERG activity.
2016, 36(3): 502-511
doi: 10.6023/cjoc201510033
Abstract:
As one of the most important methods to construct C—C bond in enantioselective manner and afford optically active β-cyano compounds, catalytic asymmetric conjugate cyanation reaction has attracted much attentions worldwide since the first report in 2003. Over the past decade, some important achievements have been made in the catalytic asymmetric conjugate cyanation of α,β-unsaturated imides, α,β-unsaturated N-acylpyrroles, α,β-unsaturated ketones, α,β-unsaturated esters, and nitroalkenes. The research progress in this field is reviewed from both metal catalysis and organocatalysis based on different Michael acceptors.
As one of the most important methods to construct C—C bond in enantioselective manner and afford optically active β-cyano compounds, catalytic asymmetric conjugate cyanation reaction has attracted much attentions worldwide since the first report in 2003. Over the past decade, some important achievements have been made in the catalytic asymmetric conjugate cyanation of α,β-unsaturated imides, α,β-unsaturated N-acylpyrroles, α,β-unsaturated ketones, α,β-unsaturated esters, and nitroalkenes. The research progress in this field is reviewed from both metal catalysis and organocatalysis based on different Michael acceptors.
2016, 36(3): 512-519
doi: 10.6023/cjoc204509001
Abstract:
Oleanolic acid (OA), a naturally occurring triterpene, was found to have a variety of biological and pharmacological properties. To expand its structural diversity, a series of oleanolic acid derivatives, including ring A and/or ring C expansion, were performed via Baeyer-Villiger reaction using m-CPBA and urea-hydrogen peroxide. The structures of all products were characterized by 1H NMR, 13C NMR and HRMS.
Oleanolic acid (OA), a naturally occurring triterpene, was found to have a variety of biological and pharmacological properties. To expand its structural diversity, a series of oleanolic acid derivatives, including ring A and/or ring C expansion, were performed via Baeyer-Villiger reaction using m-CPBA and urea-hydrogen peroxide. The structures of all products were characterized by 1H NMR, 13C NMR and HRMS.
2016, 36(3): 520-526
doi: 10.6023/cjoc201509020
Abstract:
A sequential three-component reaction for the assembly of functionalized pyrazoles is described. Aldehydes are treated with hydrazines in dichloroethane to generate hydrazones (3), which in situ take place aza-Michael reaction quickly with methyl propiolate (4) catalyzed by CuCl to give Michael adducts (5). Subsequent oxidation of 5 with stoichiometric FeCl3 provides substituted pyrazoles with high to excellent yields. The intermediates of the synthetic method are not necessary to isolate. Aliphatic hydrazines, aromatic hydrazines as well as aromatic aldehydes are well adaptable to the reaction.
A sequential three-component reaction for the assembly of functionalized pyrazoles is described. Aldehydes are treated with hydrazines in dichloroethane to generate hydrazones (3), which in situ take place aza-Michael reaction quickly with methyl propiolate (4) catalyzed by CuCl to give Michael adducts (5). Subsequent oxidation of 5 with stoichiometric FeCl3 provides substituted pyrazoles with high to excellent yields. The intermediates of the synthetic method are not necessary to isolate. Aliphatic hydrazines, aromatic hydrazines as well as aromatic aldehydes are well adaptable to the reaction.
2016, 36(3): 527-532
doi: 10.6023/cjoc201509043
Abstract:
A series of thiazolidin-4-one derivatives possessing ester were synthesized under microwave irradiation using amino acid ester as starting material. After ester hydrolysis reaction and amide condensation reaction, the aimed diaryl thiazolindin-4-one derivatives possessing amide linkage on N-3 position were obtained. The compounds were evaluated for their human immunodeficiency virus (HIV-1) reverse transcriptase (RT) inhibitory activities in vitro HIV-1 RT kit assay (colorimetric method). The results showed that some of the compounds, such as 5bb, 5bc, 5cb, and 5cc could effectively inhibit RT activity with the IC50 values of 4.15, 3.53, 4.61 and 4.06 μmol/L, respectively. Structure activity relationship analysis of these analogues suggested that the introduction of two carbons side chain on N-3 position and lipophilic group like methyl group should be favorable to their anti-HIV-RT activitives.
A series of thiazolidin-4-one derivatives possessing ester were synthesized under microwave irradiation using amino acid ester as starting material. After ester hydrolysis reaction and amide condensation reaction, the aimed diaryl thiazolindin-4-one derivatives possessing amide linkage on N-3 position were obtained. The compounds were evaluated for their human immunodeficiency virus (HIV-1) reverse transcriptase (RT) inhibitory activities in vitro HIV-1 RT kit assay (colorimetric method). The results showed that some of the compounds, such as 5bb, 5bc, 5cb, and 5cc could effectively inhibit RT activity with the IC50 values of 4.15, 3.53, 4.61 and 4.06 μmol/L, respectively. Structure activity relationship analysis of these analogues suggested that the introduction of two carbons side chain on N-3 position and lipophilic group like methyl group should be favorable to their anti-HIV-RT activitives.
2016, 36(3): 533-539
doi: 10.6023/cjoc201509024
Abstract:
A series of indolepropyl based 1,3,4-oxadiazole derivatives were synthesized by esterification, hydrazidation, cyclization and substitution using indolebutyric acid as starting material. The inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) was evaluated. The results indicated that five compounds displayed obviously inhibitory effect against PTP1B in vitro, for instance, compound 5g exhibited the strongest PTP1B inhibitory activity with an IC50 value of 6.74 μg· mL-1 . It was the first example of indolealkyl based oxadiazole derivatives showing PTP1B inhibitory activity.
A series of indolepropyl based 1,3,4-oxadiazole derivatives were synthesized by esterification, hydrazidation, cyclization and substitution using indolebutyric acid as starting material. The inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) was evaluated. The results indicated that five compounds displayed obviously inhibitory effect against PTP1B in vitro, for instance, compound 5g exhibited the strongest PTP1B inhibitory activity with an IC50 value of 6.74 μg· mL-1 . It was the first example of indolealkyl based oxadiazole derivatives showing PTP1B inhibitory activity.
2016, 36(3): 540-546
doi: 10.6023/cjoc201511001
Abstract:
1, 2, 3, 4-Tetrazine derivative is a kind of nitrogen-rich compounds, which exhibits higher energetic density and potential application on the field of energy materials. In this paper, through the [4+2] cycloaddition of α-halo-N-acylhydrazones to diazodicarboxylates, various 1, 2, 3, 4-tetrazine derivatives could be afforded in good to excellent yields in mild reaction conditions. The 1, 2-diaza-1, 3-dienes were generated in situ with the help of base, subsequently, in the absence of catalyst, the [4+2] cycloaddition proceeded well. Besides, this reaction can be performed on the gram scale and has good substrate scope.
1, 2, 3, 4-Tetrazine derivative is a kind of nitrogen-rich compounds, which exhibits higher energetic density and potential application on the field of energy materials. In this paper, through the [4+2] cycloaddition of α-halo-N-acylhydrazones to diazodicarboxylates, various 1, 2, 3, 4-tetrazine derivatives could be afforded in good to excellent yields in mild reaction conditions. The 1, 2-diaza-1, 3-dienes were generated in situ with the help of base, subsequently, in the absence of catalyst, the [4+2] cycloaddition proceeded well. Besides, this reaction can be performed on the gram scale and has good substrate scope.
2016, 36(3): 547-554
doi: 10.6023/cjoc201508021
Abstract:
Brosimacutins H and I, isolated from the bark of brosimum acutifolium huber, are flavanoid compounds with similar structures. The bark of this plant is used in Brazilian folk medicine as an anti-inflammatory and anti-rheumatic agent, and cellular activities were reported for these two compounds. Herein the first enantio-selective synthesis of brosimacutins H and I from cheap starting material hydroxyl-acetophenone and hydroxyl benzene formaldehyde was reported. All new compounds in this study were confirmed by NMR and HRMS.
Brosimacutins H and I, isolated from the bark of brosimum acutifolium huber, are flavanoid compounds with similar structures. The bark of this plant is used in Brazilian folk medicine as an anti-inflammatory and anti-rheumatic agent, and cellular activities were reported for these two compounds. Herein the first enantio-selective synthesis of brosimacutins H and I from cheap starting material hydroxyl-acetophenone and hydroxyl benzene formaldehyde was reported. All new compounds in this study were confirmed by NMR and HRMS.
2016, 36(3): 555-561
doi: 10.6023/cjoc201509045
Abstract:
A water-soluble pyridine naphthalimide-polyamidoamine dendrimer (PN-PAMAM) was synthesized by the amidation reaction of 4-(2-vinylpyridine)-1, 8-naphthalimide unit and the polyamidoamine (PAMAM). The structure was characterized by 1H NMR, 13C NMR, IR and HRMS techniques. PN-PAMAM displayed obvious aggregation-induced emission enhancement (AIEE) behavior. The experimental results demonstrated that dendrimer PN-PAMAM in solid state emitted a yellow-green fluorescence and the maximum emission wavelength was 532 nm. In aqueous solution the maximum emission wavelength was 494 nm and the fluorescence quantum yield was 4.42%. The fluorescence intensity reached the maximum at 60% water volume fraction in H2O/THF mixed solution. The fluorescence emission wavelength was 485 nm and the fluorescence quantum yield was increased to 17.54%. The photophysical properties of the silica nanoparticles loaded AIEE dye PN-PAMAM were examined. The fluorescence emission wavelength was 473 nm and the particle diameter was about 40 nm. In addition, dendrimer PN-PAMAM were applied for breast cancer MCF-7 cells imaging, getting clear blue-field photograph. In summary, the pyridine naphthalimide-PAMAM dendrimer is a water-soluble fluorescent dye and displays AIEE behavior. PN-PAMAM can be widely used in areas of tumor localization, bio-tracking and nano-materials.
A water-soluble pyridine naphthalimide-polyamidoamine dendrimer (PN-PAMAM) was synthesized by the amidation reaction of 4-(2-vinylpyridine)-1, 8-naphthalimide unit and the polyamidoamine (PAMAM). The structure was characterized by 1H NMR, 13C NMR, IR and HRMS techniques. PN-PAMAM displayed obvious aggregation-induced emission enhancement (AIEE) behavior. The experimental results demonstrated that dendrimer PN-PAMAM in solid state emitted a yellow-green fluorescence and the maximum emission wavelength was 532 nm. In aqueous solution the maximum emission wavelength was 494 nm and the fluorescence quantum yield was 4.42%. The fluorescence intensity reached the maximum at 60% water volume fraction in H2O/THF mixed solution. The fluorescence emission wavelength was 485 nm and the fluorescence quantum yield was increased to 17.54%. The photophysical properties of the silica nanoparticles loaded AIEE dye PN-PAMAM were examined. The fluorescence emission wavelength was 473 nm and the particle diameter was about 40 nm. In addition, dendrimer PN-PAMAM were applied for breast cancer MCF-7 cells imaging, getting clear blue-field photograph. In summary, the pyridine naphthalimide-PAMAM dendrimer is a water-soluble fluorescent dye and displays AIEE behavior. PN-PAMAM can be widely used in areas of tumor localization, bio-tracking and nano-materials.
2016, 36(3): 562-571
doi: 10.6023/cjoc201508032
Abstract:
Pheophorbide-a and b methyl esters, as initial degraded products from chlorophyll-a and b, were used as starting materials, and the hydroxylmethylic or formylic structures were established making use of the active reaction regions on chlorin periphery by some common reactions, such as aldol condensation, allomerization, oxidant oxidation. The methylene or vinyl groups possessing higher reactivity were introduced at different site around chlorin pericycle by Grignard reavtion, acid-catalyzed dehydration and rearrangement reaction in E-ring. A series of unreported chlorophyllous chlorins substituted by multi-terminal alkenyl group were synthesized and their chemical structures were characterized by elemental analysis, UV, IR and 1H NMR spectra. The in vitro photosensitive bactericidal activities of new chlorins were discussed and the possible mechanisms about corresponding reactions were tentatively proposed.
Pheophorbide-a and b methyl esters, as initial degraded products from chlorophyll-a and b, were used as starting materials, and the hydroxylmethylic or formylic structures were established making use of the active reaction regions on chlorin periphery by some common reactions, such as aldol condensation, allomerization, oxidant oxidation. The methylene or vinyl groups possessing higher reactivity were introduced at different site around chlorin pericycle by Grignard reavtion, acid-catalyzed dehydration and rearrangement reaction in E-ring. A series of unreported chlorophyllous chlorins substituted by multi-terminal alkenyl group were synthesized and their chemical structures were characterized by elemental analysis, UV, IR and 1H NMR spectra. The in vitro photosensitive bactericidal activities of new chlorins were discussed and the possible mechanisms about corresponding reactions were tentatively proposed.
2016, 36(3): 572-579
doi: 10.6023/cjoc201510016
Abstract:
29 novel 3-substituted-benzoyl-4-substituted-thienyl-pyrrole compounds 2a~5c were synthesized via aldol condensation and Van Leusen pyrrole reaction using substituted acetophenone and substituted 2-thenaldehyde as raw materials, and the cell proliferation inhibition efficacy of 2a~5c against human colon cancer (HCT-116), human gastric adenocarcinoma (SGC-7901), human cervical carcinoma (Hela) and human umbilical vein endothelial (HUVEC) cell lines were estimated. Then MTT assay was used to evaluate the anti-proliferative activity. The result indicated that some target compounds exhibited strong (IC50≤20 μmol·L-1) or moderate (20 μmol·L-1 < IC50≤50 μmol·L-1) proliferation inhibition efficacy against tumor cells, meanwhile didn't have significate inhibition effect on HUVEC. Compounds 2c, 2i, 3i, 3j, 4a~4f and 5c showed strong or moderate inhibition efficacy against HCT-116. The IC50 value of 2j was 4.3 μmol·L-1 against Hela, and compounds 2i and 3jexhibited moderate inhibition efficacy against Hela. The IC50 value of 3j was 10.5 μmol·L-1 against SGC-7901, and compounds 2iindicated moderate inhibition efficacy against SGC-7901. Compounds 2iand 3j showed broad anti-proliferative activity against all selected tumor cells.
29 novel 3-substituted-benzoyl-4-substituted-thienyl-pyrrole compounds 2a~5c were synthesized via aldol condensation and Van Leusen pyrrole reaction using substituted acetophenone and substituted 2-thenaldehyde as raw materials, and the cell proliferation inhibition efficacy of 2a~5c against human colon cancer (HCT-116), human gastric adenocarcinoma (SGC-7901), human cervical carcinoma (Hela) and human umbilical vein endothelial (HUVEC) cell lines were estimated. Then MTT assay was used to evaluate the anti-proliferative activity. The result indicated that some target compounds exhibited strong (IC50≤20 μmol·L-1) or moderate (20 μmol·L-1 < IC50≤50 μmol·L-1) proliferation inhibition efficacy against tumor cells, meanwhile didn't have significate inhibition effect on HUVEC. Compounds 2c, 2i, 3i, 3j, 4a~4f and 5c showed strong or moderate inhibition efficacy against HCT-116. The IC50 value of 2j was 4.3 μmol·L-1 against Hela, and compounds 2i and 3jexhibited moderate inhibition efficacy against Hela. The IC50 value of 3j was 10.5 μmol·L-1 against SGC-7901, and compounds 2iindicated moderate inhibition efficacy against SGC-7901. Compounds 2iand 3j showed broad anti-proliferative activity against all selected tumor cells.
2016, 36(3): 580-589
doi: 10.6023/cjoc201506037
Abstract:
Pyropheophorbide-a methyl ester was used as a starting material, and its oxygenations were carried out by thaillum nitrate and air as oxidizing agent to introduce the formyl group and the formylmethyl group at 3-, 12-or 15-postion of chlorin periphery, respectively. After oximation these aldehyde groups were converted into cyano group under the reaction mediated from N, N-dimethylformamide and 2, 4, 6-trichloro-1, 3, 5-triazine. Dicyanomethylene moiety was established by Knoevenagel reaction of malononitrile with formyl group and 131-carbounyl group on the exocyclic ring. Mulcyano-substitutions on the chromophore were accomplished by further structure modifications. A series of unreported chlorins related to chlorophyll substituted with cyano-group were synthesized making use of cyanation at different positions on the periphery of chlorophyll degradation products. Their chemical structures were characterized by elemental analysis, UV, IR and1H NMR spectra. The reaction mechanisms on the cyanation for the chlorophyllous chlorins were discussed and in vitro photodynamic activities of some new compounds were determined.
Pyropheophorbide-a methyl ester was used as a starting material, and its oxygenations were carried out by thaillum nitrate and air as oxidizing agent to introduce the formyl group and the formylmethyl group at 3-, 12-or 15-postion of chlorin periphery, respectively. After oximation these aldehyde groups were converted into cyano group under the reaction mediated from N, N-dimethylformamide and 2, 4, 6-trichloro-1, 3, 5-triazine. Dicyanomethylene moiety was established by Knoevenagel reaction of malononitrile with formyl group and 131-carbounyl group on the exocyclic ring. Mulcyano-substitutions on the chromophore were accomplished by further structure modifications. A series of unreported chlorins related to chlorophyll substituted with cyano-group were synthesized making use of cyanation at different positions on the periphery of chlorophyll degradation products. Their chemical structures were characterized by elemental analysis, UV, IR and1H NMR spectra. The reaction mechanisms on the cyanation for the chlorophyllous chlorins were discussed and in vitro photodynamic activities of some new compounds were determined.
2016, 36(3): 590-595
doi: 10.6023/cjoc201508019
Abstract:
A series of novel trans-2, 3, 6(8)-trisubstituted-1, 3-benzoxazines were prepared in yields of 38%~80% by reactions of 2-arylaminomethyl phenols with various substituted benzaldehydes in the presence of TMSCl. The reaction showed high trans selectivity. The structures of all the target products were characterized by 1H NMR, 13C NMR, IR and elemental analysis. The fungicidal activities of the prepared compounds were investigated, most of which showed moderate to good activity, compounds 5d and 5f showed growth inhibition of 78.6% against M. oryzae at 50 mg/mL.
A series of novel trans-2, 3, 6(8)-trisubstituted-1, 3-benzoxazines were prepared in yields of 38%~80% by reactions of 2-arylaminomethyl phenols with various substituted benzaldehydes in the presence of TMSCl. The reaction showed high trans selectivity. The structures of all the target products were characterized by 1H NMR, 13C NMR, IR and elemental analysis. The fungicidal activities of the prepared compounds were investigated, most of which showed moderate to good activity, compounds 5d and 5f showed growth inhibition of 78.6% against M. oryzae at 50 mg/mL.
2016, 36(3): 596-603
doi: 10.6023/cjoc201510014
Abstract:
A piperidinium acetate-catalyzed method was developed for the Knoevenagel and O-Micheal cascade reaction of o-hydroxyphenyl-β-diketoes with different series of aldehydes. In the presence of piperidinium acetate, sixteen 2, 3-disub-stituted chroman-4-ones and nine 2, 2-disubstituted benzofuran-3-ones were obtained in moderate to good yields, and the cascade reaction displayed better substrate adaptability. Moreover, the reaction has the following features: a convenient and simple path, mild reaction conditions and a cheap catalyst.
A piperidinium acetate-catalyzed method was developed for the Knoevenagel and O-Micheal cascade reaction of o-hydroxyphenyl-β-diketoes with different series of aldehydes. In the presence of piperidinium acetate, sixteen 2, 3-disub-stituted chroman-4-ones and nine 2, 2-disubstituted benzofuran-3-ones were obtained in moderate to good yields, and the cascade reaction displayed better substrate adaptability. Moreover, the reaction has the following features: a convenient and simple path, mild reaction conditions and a cheap catalyst.
2016, 36(3): 604-612
doi: 10.6023/cjoc201508003
Abstract:
A novel series of cyclopropane-bearing C-glucosides were designed and synthesized as sodium-glucose cotransporter 2 (SGLT2) inhibitors starting from the substituted bromobenzoic acids. The reaction condition for the construction of the cyclopropane moiety was studied, and a more economical synthetic route was established. All the synthesized compounds were characterized by 1H NMR and HR-MS. In vivo evaluation of these compounds by rat urinary glucose excretion (UGE) test revealed that all the synthesized seven cyclopropane-bearing C-glucosides 1a~1g exhibited potent hypoglycemic activity, among which (1S)-1-deoxy-1-{4-chloro-3-[1-(4-ethoxyphenyl)cyclopropyl-1-yl]-phenyl}-D-glucopyranose (1e) was the most potent one but still exhibited lower hypoglycemic activity to dapagliflozin, demonstrating that the cyclopropane moiety can not be well tolerated in dapagliflozin molecule and the position of the Cl atom in dapagliflozin is the best among the analogues.
A novel series of cyclopropane-bearing C-glucosides were designed and synthesized as sodium-glucose cotransporter 2 (SGLT2) inhibitors starting from the substituted bromobenzoic acids. The reaction condition for the construction of the cyclopropane moiety was studied, and a more economical synthetic route was established. All the synthesized compounds were characterized by 1H NMR and HR-MS. In vivo evaluation of these compounds by rat urinary glucose excretion (UGE) test revealed that all the synthesized seven cyclopropane-bearing C-glucosides 1a~1g exhibited potent hypoglycemic activity, among which (1S)-1-deoxy-1-{4-chloro-3-[1-(4-ethoxyphenyl)cyclopropyl-1-yl]-phenyl}-D-glucopyranose (1e) was the most potent one but still exhibited lower hypoglycemic activity to dapagliflozin, demonstrating that the cyclopropane moiety can not be well tolerated in dapagliflozin molecule and the position of the Cl atom in dapagliflozin is the best among the analogues.
2016, 36(3): 613-621
doi: 10.6023/cjoc201508026
Abstract:
The reaction mechanism for N-methylindole and keto ester catalyzed by InX3 (X=F, Br) was studied by the density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states, and products have been calculated at the B3LYP/6-31+G(d, p) level, dichloroethane (DCE) is used as a solvent and the LanL2DZ basis has been used for In atom. Transition states have been confirmed by the corresponding vibration analysis and intrinsic reaction coordinate (IRC). In addition, nature bond orbital (NBO) and atoms in molecules (AIM) theories have been used to analyze orbital interactions and bond natures. The results showed that the activation energies of rate-determining steps in which N-methylindole reacted with keto ester to form 1,2-adduct and 1,4-adduct were 25.62 and 12.52 kcal/mol catalyzed by InF3 while those were 26.87 and 13.95 kcal/mol when the reaction was catalyzed by InBr3 under the same conditions. Comparing the results of our research, InF3 can effectively catalyze the reaction, and the 1,4-adduct was more likely to be produced. The final result of our theory study agreed with the experimental data, meanwhile, self-consistent reaction field (SCRF) was carried out using the polarized continuum model (PCM) at the same theoretical level for geometry optimizations and frequency calculations in five different salvations. We predicted that the productivity to form 1,4-adduct was more higher catalyzed by InF3 in the solvent of dimethyl sulfoxide (DMSO).
The reaction mechanism for N-methylindole and keto ester catalyzed by InX3 (X=F, Br) was studied by the density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states, and products have been calculated at the B3LYP/6-31+G(d, p) level, dichloroethane (DCE) is used as a solvent and the LanL2DZ basis has been used for In atom. Transition states have been confirmed by the corresponding vibration analysis and intrinsic reaction coordinate (IRC). In addition, nature bond orbital (NBO) and atoms in molecules (AIM) theories have been used to analyze orbital interactions and bond natures. The results showed that the activation energies of rate-determining steps in which N-methylindole reacted with keto ester to form 1,2-adduct and 1,4-adduct were 25.62 and 12.52 kcal/mol catalyzed by InF3 while those were 26.87 and 13.95 kcal/mol when the reaction was catalyzed by InBr3 under the same conditions. Comparing the results of our research, InF3 can effectively catalyze the reaction, and the 1,4-adduct was more likely to be produced. The final result of our theory study agreed with the experimental data, meanwhile, self-consistent reaction field (SCRF) was carried out using the polarized continuum model (PCM) at the same theoretical level for geometry optimizations and frequency calculations in five different salvations. We predicted that the productivity to form 1,4-adduct was more higher catalyzed by InF3 in the solvent of dimethyl sulfoxide (DMSO).
2016, 36(3): 622-625
doi: 10.6023/cjoc201509033
Abstract:
Using benzothiophene-2-carboxylic acid as a raw material, 2-(1-benzothiophen-2-yl)-4H-1,3,4-oxadiazin-5(6H)-one (4) was synthesized by esterification and hydrazinolysis, followed by the acylation and cyclization reactions. The novel compound 4 was characterized by 1H NMR, 13C NMR, ESI-MS, FT-IR, elemental analysis and X-ray single crystal diffraction.
Using benzothiophene-2-carboxylic acid as a raw material, 2-(1-benzothiophen-2-yl)-4H-1,3,4-oxadiazin-5(6H)-one (4) was synthesized by esterification and hydrazinolysis, followed by the acylation and cyclization reactions. The novel compound 4 was characterized by 1H NMR, 13C NMR, ESI-MS, FT-IR, elemental analysis and X-ray single crystal diffraction.
2016, 36(3): 626-629
doi: 10.6023/cjoc201511002
Abstract:
Studies on the formation of silaimines are among the most fascinating topics in organosilicon chemistry. The first route to silaimine via eliminaition of Me3SiCl from diaminochlorosilanes is reported. Reaction of aminodichlorosilane ArN(SiMe3)SiHCl2 (1) (Ar=2,6-i-Pr2C6H3) with ArN(SiMe3)Li in Et2O at -78 ℃ followed by stirring the mixture for 5 h at room temperature afforded diaminochlorosilane [ArN(SiMe3)]2SiHCl (2). Compound 2 has been fully characterized by 1H NMR, 13C NMR, 29Si NMR, IR and elemental analysis. Reactivity of 2 with different N-heterocyclic carbenes has been examined. It was found that 2 did not react with sterically hindered N-heterocyclic carbenes (NHC), 3-tert-butylimidazol-2-ylidene (ItBu) and 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (IiPr) at room temperature or under reflux conditions. However, compound 2 could react with one equivalent of 1,3,4,5-tetramethyl-imidazol-2-ylidene (IMe4) to give base-stabilized 1-hydrosilaimine 3. Compound 3 can be viewed as the elimination product from 2 through loss of Me3SiCl, as the small IMe4 coordinate to 2 to form a hypervalent silicon species.
Studies on the formation of silaimines are among the most fascinating topics in organosilicon chemistry. The first route to silaimine via eliminaition of Me3SiCl from diaminochlorosilanes is reported. Reaction of aminodichlorosilane ArN(SiMe3)SiHCl2 (1) (Ar=2,6-i-Pr2C6H3) with ArN(SiMe3)Li in Et2O at -78 ℃ followed by stirring the mixture for 5 h at room temperature afforded diaminochlorosilane [ArN(SiMe3)]2SiHCl (2). Compound 2 has been fully characterized by 1H NMR, 13C NMR, 29Si NMR, IR and elemental analysis. Reactivity of 2 with different N-heterocyclic carbenes has been examined. It was found that 2 did not react with sterically hindered N-heterocyclic carbenes (NHC), 3-tert-butylimidazol-2-ylidene (ItBu) and 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (IiPr) at room temperature or under reflux conditions. However, compound 2 could react with one equivalent of 1,3,4,5-tetramethyl-imidazol-2-ylidene (IMe4) to give base-stabilized 1-hydrosilaimine 3. Compound 3 can be viewed as the elimination product from 2 through loss of Me3SiCl, as the small IMe4 coordinate to 2 to form a hypervalent silicon species.
2016, 36(3): 630-637
doi: 10.6023/cjoc201509021
Abstract:
Using dehydroepiandrosterone as starting material, 16 dehydroepiandrosteronyl thiazol derivatives with different structures had been synthesized via microwave irradiation assisted one-pot reaction and general synthetic method, and their structures were characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds was evaluated against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T). The results showed that compound 4 displayed significant inhibitory activity to tested cancer cells, and the values of IC50 were 13.2, 11.3 and 8.3 μmol·L-1 respectively, but was almost inactive to HEK293T cells (IC50>100 μmol·L-1). However, other compounds did not exhibit distinct antiproliferative activity to all tested cells.
Using dehydroepiandrosterone as starting material, 16 dehydroepiandrosteronyl thiazol derivatives with different structures had been synthesized via microwave irradiation assisted one-pot reaction and general synthetic method, and their structures were characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds was evaluated against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T). The results showed that compound 4 displayed significant inhibitory activity to tested cancer cells, and the values of IC50 were 13.2, 11.3 and 8.3 μmol·L-1 respectively, but was almost inactive to HEK293T cells (IC50>100 μmol·L-1). However, other compounds did not exhibit distinct antiproliferative activity to all tested cells.
2016, 36(3): 638-641
doi: 10.6023/cjoc201509023
Abstract:
A novel phenanthrene oxide, named 4,7-dimethoxy-phenanthrene-1,2-dione (1), and other five known phenanthrene derivatives were isolated from the tubers of Bletilla striata. The structures of the new compounds were established by means of HR-ESIMS, 1D and 2D NMR.
A novel phenanthrene oxide, named 4,7-dimethoxy-phenanthrene-1,2-dione (1), and other five known phenanthrene derivatives were isolated from the tubers of Bletilla striata. The structures of the new compounds were established by means of HR-ESIMS, 1D and 2D NMR.
2016, 36(3): 642-647
doi: 10.6023/cjoc201508008
Abstract:
To obtain new herbicidal candidates with novel structure and high herbicidal activities, six new pyrazol compounds based on the structure of tembotrione were designed and synthesized. The meta substituent of benzene ring and the cyclohexadione ring in the original tembotrione structure are replaced. The six target compounds were achieved with 3-chloro-2-methylaniline as the starting material after nine steps reactions, namely diazotization, acetylization, oxidation, esterization, bromization, nucleophilic substitution, chlorination and condensation reactions. All the structures of target products and their intermediates are characterized and confirmed by 1H NMR, 13C NMR, FTIR and elemental analysis. Herbicidal activity tests are also conducted for the six compounds. The results show that each compound exhibits certain herbicidal activity toward mustard, chickweed, amur foxtail, chenopodium and polypogon fugax.
To obtain new herbicidal candidates with novel structure and high herbicidal activities, six new pyrazol compounds based on the structure of tembotrione were designed and synthesized. The meta substituent of benzene ring and the cyclohexadione ring in the original tembotrione structure are replaced. The six target compounds were achieved with 3-chloro-2-methylaniline as the starting material after nine steps reactions, namely diazotization, acetylization, oxidation, esterization, bromization, nucleophilic substitution, chlorination and condensation reactions. All the structures of target products and their intermediates are characterized and confirmed by 1H NMR, 13C NMR, FTIR and elemental analysis. Herbicidal activity tests are also conducted for the six compounds. The results show that each compound exhibits certain herbicidal activity toward mustard, chickweed, amur foxtail, chenopodium and polypogon fugax.
2016, 36(3): 648-652
doi: 10.6023/cjoc201508027
Abstract:
A method for the synthesis of the isorhapontigenin and the stilbene compounds in similar structures was developed. Using 3,5-dihydroxybenzoic acid as starting material, benzyl protecting the phenolic hydroxyl, via the Wittig-Horner reaction to construct the trans stilbene structure, and then debenzylation under the palladium on carbon/ammonium formate system condition, the isorhapontigenin could be obtained in the yield of up to 48%. The catalytic system was successfully applied in the synthesis of a series of hydroxyl stilbene compounds, which could achieve good results. All the reactions worked under mild conditions and obtained in good yield. Furthermore the materials were of cheap and less toxicity. It provided us a simple way to synthesize hydroxyl stilbene compounds in large scale.
A method for the synthesis of the isorhapontigenin and the stilbene compounds in similar structures was developed. Using 3,5-dihydroxybenzoic acid as starting material, benzyl protecting the phenolic hydroxyl, via the Wittig-Horner reaction to construct the trans stilbene structure, and then debenzylation under the palladium on carbon/ammonium formate system condition, the isorhapontigenin could be obtained in the yield of up to 48%. The catalytic system was successfully applied in the synthesis of a series of hydroxyl stilbene compounds, which could achieve good results. All the reactions worked under mild conditions and obtained in good yield. Furthermore the materials were of cheap and less toxicity. It provided us a simple way to synthesize hydroxyl stilbene compounds in large scale.
2016, 36(3): 653-658
doi: 10.6023/cjoc201509015
Abstract:
The interaction and supramolecular self-assembly of cucurbit[7]uril (Q[7]) with 2,2'-(heptane-1,7-diyl) dibenzimidazolium chloride (SBHt) in aqueous solution were investigated by 1H NMR spectroscopy, fluorescence spectroscopy in details. The pKa shift of guest in the presence of Q[7] was first investigated in order to decide the pH of medium condition for investigation of host-guest interaction and supramolecular self-assembly. 1H NMR spectroscopy analysis revealed that Q[7] included the alkylene chain of guest and formed a simple 1:1 host-guest binding model complex at a low rate of NQ[7]/NSBHt, while at higher ratios of Q[7] to guest, two host Q[7] prefer to include the benzimidazolyl moieties of guest and formed a dumbbell shape inclusion complex. The typical reversible interaction modes were controlled by concentration of the ratio of host and guest, and the process was further conformed by fluorescence spectroscopy technology. The single X-ray crystal structure analysis showed a 1:1 host-guest inclusion complex in which the alkyl chain of SBHt was folded in order to effectively interact with Q[7] through ion-dipole interactions and hydrogen bonding.
The interaction and supramolecular self-assembly of cucurbit[7]uril (Q[7]) with 2,2'-(heptane-1,7-diyl) dibenzimidazolium chloride (SBHt) in aqueous solution were investigated by 1H NMR spectroscopy, fluorescence spectroscopy in details. The pKa shift of guest in the presence of Q[7] was first investigated in order to decide the pH of medium condition for investigation of host-guest interaction and supramolecular self-assembly. 1H NMR spectroscopy analysis revealed that Q[7] included the alkylene chain of guest and formed a simple 1:1 host-guest binding model complex at a low rate of NQ[7]/NSBHt, while at higher ratios of Q[7] to guest, two host Q[7] prefer to include the benzimidazolyl moieties of guest and formed a dumbbell shape inclusion complex. The typical reversible interaction modes were controlled by concentration of the ratio of host and guest, and the process was further conformed by fluorescence spectroscopy technology. The single X-ray crystal structure analysis showed a 1:1 host-guest inclusion complex in which the alkyl chain of SBHt was folded in order to effectively interact with Q[7] through ion-dipole interactions and hydrogen bonding.
2016, 36(3): 659-663
doi: 10.6023/cjoc201509037
Abstract:
A series of pyrano[2,3-d]pyrimidine derivatives were synthesized by the reaction of 2-amino-3-cyano-4H-pyrans with acetic anhydride. This method has the advantages of short reaction times (10~15 min), simple operation and convenient post-treatment. All products were fully characterized by IR and 1H NMR spectra. The molecular structures of 4a and 6a were confirmed using single-crystal X-ray analyses.
A series of pyrano[2,3-d]pyrimidine derivatives were synthesized by the reaction of 2-amino-3-cyano-4H-pyrans with acetic anhydride. This method has the advantages of short reaction times (10~15 min), simple operation and convenient post-treatment. All products were fully characterized by IR and 1H NMR spectra. The molecular structures of 4a and 6a were confirmed using single-crystal X-ray analyses.
2016, 36(3): 664-669
doi: 10.6023/cjoc201509042
Abstract:
In order to obtain antitumor candidates with potent activity, two novel analogues of dihydrofolate reductase (DHFR) inhibitors 3c and 4b were designed and synthesized. The synthetic routes were as follows: 1c was synthesized using chloroacetonitrile, carboxylate and 2,4,6-triamino-pyrimidine as raw materials by condensation, cyclization and reduction. 2d was synthesized using 2-thiophene formaldehyde and glutamate as raw materials by nitrification, oxidation, condensation and reduction. Then target product 3c was synthesized using 1c and 2d as raw materials by reductive amination and hydrolysis. Target product 4b was synthesized using 1c and 2d as raw materials by 2 steps of reductive amination and hydrolysis. The structures of target products were confirmed by the way of 1H NMR, 13C NMR and MS. The in vitro antitumor activities of target products were evaluated by MTT method. The results showed that 3c exhibited stronger antitumor activity against screened five tumor cell lines (CCRF-CEM, L1210, A549, SGC-7901 and Hep-G2) than the positive control lometrexol, methotrexate and pemetrexed. 3c exhibited stronger antitumor activity against Hep-G2 than the positive control lometrexol, methotrexate and pemetrexed. In addition, 3c and 4b showed much weaker antiproliferative activity toward normal cell SMC than the positive control methotrexate and pemetrexed. This research could provide a theoretical basis for the development of new antitumor drugs.
In order to obtain antitumor candidates with potent activity, two novel analogues of dihydrofolate reductase (DHFR) inhibitors 3c and 4b were designed and synthesized. The synthetic routes were as follows: 1c was synthesized using chloroacetonitrile, carboxylate and 2,4,6-triamino-pyrimidine as raw materials by condensation, cyclization and reduction. 2d was synthesized using 2-thiophene formaldehyde and glutamate as raw materials by nitrification, oxidation, condensation and reduction. Then target product 3c was synthesized using 1c and 2d as raw materials by reductive amination and hydrolysis. Target product 4b was synthesized using 1c and 2d as raw materials by 2 steps of reductive amination and hydrolysis. The structures of target products were confirmed by the way of 1H NMR, 13C NMR and MS. The in vitro antitumor activities of target products were evaluated by MTT method. The results showed that 3c exhibited stronger antitumor activity against screened five tumor cell lines (CCRF-CEM, L1210, A549, SGC-7901 and Hep-G2) than the positive control lometrexol, methotrexate and pemetrexed. 3c exhibited stronger antitumor activity against Hep-G2 than the positive control lometrexol, methotrexate and pemetrexed. In addition, 3c and 4b showed much weaker antiproliferative activity toward normal cell SMC than the positive control methotrexate and pemetrexed. This research could provide a theoretical basis for the development of new antitumor drugs.
