CN108558895B - Isatin mother nucleus peroxide compound with antibacterial activity and preparation method thereof - Google Patents
Isatin mother nucleus peroxide compound with antibacterial activity and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an isatin mother nucleus peroxide compound with bacteriostatic activity, which is shown in a structural general formula (I), wherein R1Selected from hydrogen, halogen or C1-C3 alkane, R2Selected from hydrogen, methyl, phenyl. The compound is obtained by taking isatin or derivatives thereof and dicarbonyl compound as raw materials and reacting in an organic solvent. The method has high operation safety and mild reaction conditions, and is suitable for industrial production. Preliminary biological activity tests show that the compound has good bacteriostatic activity and important medical application value.
Description
Technical Field
The invention relates to an isatin mother nucleus peroxide compound with antibacterial activity and a preparation method thereof, belonging to the field of medical chemistry.
Background
Isatin (1H-indole-2, 3-dione) has developed into a parent nucleus structure essential in many dyes, pesticides and medicines due to its unique size, unique electronic properties and superior biological activity, and its versatility attracts people's attention. The synthesis and structure modification of isatin and derivatives thereof become a hotspot in the research and development of new drugs at present, and isatin derivatives with various structures are generated at the same time. Sunitinib is an oral tyrosine kinase inhibitor that was approved in 2006 for the treatment of metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Furthermore, Intedanib was developed as a potential anticancer drug acting as a triple vascular kinase inhibitor of VEGFR, PDGFR and FGFR. Semaxanib and TSU-68 have also been found to have good anti-cancer properties in a series of small molecule lead compounds known as multi-target tyrosine kinase inhibitors. Structurally, both Semaxanib and TSU-68 are closely related analogs of sunitinib, which all contain the core skeleton of isatin.
Furthermore, the isatin nucleus is also frequently present in many bisisatin compounds. Indigo isomer-indirubin, although it is less in natural herb indigo, is an activity of Chinese patent medicine angelica longhui pillsIngredient for the treatment of chronic myeloid leukemia. The indirubin analog methylisoindigo (Meisoindigo) is also very good in treating chronic granulocytic leukemia (CP), and the treatment effect of the methylisoindigo is equivalent to that of hydroxyurea and busulfan. Indirubin compounds are identified as inhibitors of cyclin dependent protein kinases (CDKs) and GSK-3 beta, their IC for CDK2 and GSK-3 beta502.2. mu.M and 0.19. mu.M, respectively. At the same time, it can inhibit CDK5 and GSK-3 beta mediated tau protein phosphorylation process which is overactive in Alzheimer disease.
Dioxygen is present in many compounds, and artemisinin ring also has a dioxygen bond (-O-O-), which is an important pharmacophore for the treatment of malaria, and which destroys the internal structure of the malarial parasite and kills it.
Disclosure of Invention
The invention aims to provide an isatin mother nucleus peroxide compound with bacteriostatic activity and a synthesis method thereof.
The invention is realized as follows:
a compound shown in a structural general formula (I),
wherein R is1Selected from hydrogen, halogen or C1-C3 alkane, R2Selected from hydrogen, methyl, phenyl.
The structural formulae for the compounds of some preferred embodiments of the present invention are shown below:
a preparation method of a compound shown in a structural general formula (I),
taking isatin or a derivative A thereof and a dicarbonyl compound B as raw materials, and synthesizing in an organic solvent under the action of a catalyst to obtain a compound shown in a structural general formula (I).
Specifically, the preparation method comprises the following steps:
(1) the molar ratio of the isatin or the derivative A thereof to the dicarbonyl compound B is 1 (1-1.2), adding an organic solvent, adding DMF (1/5-1/20 volume of the organic solvent), adding a catalytic amount of catalyst, and carrying out reflux reaction at 80-120 ℃;
(2) and tracking the reaction to be complete by a thin-layer chromatography method, stopping heating, evaporating the solid-liquid mixture of the reaction system under reduced pressure to remove the solvent, cooling to room temperature, filtering, washing the filter cake with an organic solvent to obtain a crude product of the isatin mother nucleus peroxide, and further recrystallizing to obtain the target product.
The feeding ratio in the step (1) is that the molar ratio of the isatin or the derivative A thereof to the dicarbonyl compound B is 1: 1.2.
The organic solvent in the step (1) is selected from toluene, carbon tetrachloride and 1, 2-dichloroethane, and is preferably toluene.
The catalyst in the step (1) can be selected from a combination of an oxidant and an acidic substance, specifically an oxidant KMnO4/MnO2、O3、H2O2With an acidic substance AlCl3、ZnCl2And one of macroporous strong-acid styrene ion resin, and further optimized into H2O2And a strongly acidic ionic resin D001.
The reaction time in the step (1) is preferably 6 to 12 hours.
The reaction temperature in the step (1) is preferably 90-120 ℃.
The invention has the advantages that: the method has the advantages of easily available raw materials, low production cost, high operation safety, environment-friendly and mild reaction conditions, can realize the full utilization of reaction raw materials, and is suitable for industrial production.
Detailed Description
The present invention is further illustrated below with reference to specific examples, which are provided for illustrative purposes only and do not limit the scope and spirit of the present invention.
Example 1
Preparation of 1- (3-methyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized in the following reaction scheme).
200mg (1.36mmol) of isatin and 163.1mg (1.63mmol) of 2, 4-pentanedione were charged into a reactor, 50mL of 1, 2-dichloroethane and 5mL of DMF were added as a reaction solvent, and 1mLH was added2O2And 13.6mg AlCl3As a catalyst, the electric heating jacket is heated to 100 ℃, and the reaction is carried out for 12 hours under the magnetic stirring and reflux. After the completion of the reaction by thin layer chromatography, the solvent was distilled off under reduced pressure, and the cake was washed with 1, 2-dichloroethane and dried to obtain 219.9mg of the objective compound in a total yield of 70.6%.
1H-NMR (300MHz, DMSO-d 6 ) δ (ppm): 9.83(2H, s), 8.77(1H,d), 8.34(1H,d), 8.05(1H,m), 7.92(1H,t), 2.93(3H,s), 1.94(3H,s); (hydrochloride) 13C-NMR (75MHz, DMSO-d 6) δ (ppm): 166.7, 154.6, 143.7, 137.8, 137.6, 128.9, 128.8, 122.5, 118.9, 118.8, 24.4, 21.7; MS (ESI) for (M+H)+: 230.1。
Example 2
Preparation of 1- (6-chloro-3-methyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized in the following reaction scheme).
181mg (1.0mmol) of 5-chloroisatin and 120.1mg (1.2mmol) of 2, 4-pentanedione were charged into a reactor, 50mL of toluene and 5mL of DMF were added as reaction solvents, and 1mL of H was added2O2And 20mg of strong acid ion resin D001 as a catalyst, heating the mixture to 110 ℃ by an electric heating jacket, and carrying out reflux reaction for 10 hours by magnetic stirring. After the completion of the reaction by thin layer chromatography, the solvent was distilled off under reduced pressure, and the filter cake was washed with toluene and dried to obtain 195.9mg of the objective compound in a total yield of 74.5%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.25 (1H, s), 7.63（1H, s）, 7.45 (1H, d),7.16 (1H,d), 2.27（3H,s）, 2.12（3H，s）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):168.5, 162.3, 146.7, 128.5, 125.6, 123.4, 121.7, 118.1, 109.4, 28.9, 11.8; MS (ESI) for (M+Na)+: 286.0。
Example 3
Preparation of 1- (3,6-dimethyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized according to the following reaction scheme).
193.2mg (1.2mmol) of 5-methyl-isatin and 144.1mg (1.44mmol) of 2, 4-pentanedione were charged into a reactor, 50mL of tetrahydrofuran and 5mL of DMF were added as a reaction solvent, and 12.1mg of KMnO was added4、6.7 mg MnO2And 20mg of strong acid ion resin D001 as a catalyst, heating the mixture to 80 ℃ by an electric heating sleeve, and carrying out reflux reaction for 12 hours under magnetic stirring. After the thin layer chromatography is tracked until the reaction is completed, the solvent is evaporated under reduced pressure, and a filter cake is washed by tetrahydrofuran and dried to obtain the target compound 196.0mg with the total yield of 67.2%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.87 (1H,s), 7.81（1H,s）, 7.65 (1H,d),7.15 (1H,d), 2.34（3H,s）, 2.28（3H,s）, 2.24（3H，s）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):187.3, 185.1, 153.8, 139.5, 128.9, 126.2, 120.8, 111.1, 108.5, 91.1, 22.9, 20.7, 10.8; MS (ESI) for (M+H)+: 244.1。
Example 4
preparation of phenyl (3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) methanone (corresponding to the product synthesized by the following reaction scheme).
Into a reactor were charged 102.9mg (0.7mmol) of isatin and 188.2mg (0.84mmol) of 1, 3-diphenyl-1, 3-propanedione, and 50mL of 1, 2-dichloroethane and 5mL of DMF were added as reaction solutionsAgent, 1mL of H2O2And 20mg of strongly acidic ionic resin D001 as a catalyst, heating to 90 ℃ by an electric heating jacket, and carrying out reflux reaction for 11 hours by magnetic stirring. After the thin layer chromatography tracking is carried out until the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained mixture is separated and purified by silica gel column chromatography and dried to obtain 147.8mg of the target compound with the total yield of 59.8%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.55(1H,s),6.91~7.92（4H,m）, 7.23~7.67（5H,m）, 7.62~7.78（5H,m）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):188.5, 158.2, 142.5, 135.9, 134.5, 130.9, 129.2, 127.9, 124.0, 122.7, 119.8, 115.0, 111.3, 100.9, 93.1; MS (ESI) for (M+Na)+: 376.1。
Example 5
Preparation of (6-chloro-3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) (phenyl) methanone (corresponding to the product synthesized in the following reaction scheme).
108.6mg (0.6mmol) of 5-chloro-isatin and 161.3mg (0.72mmol) of 1, 3-diphenyl-1, 3-propanedione are charged into the reactor, 50mL of tetrahydrofuran and 5mL of DMF are added as reaction solvent, 1mL of H are added2O2And 13.4mg of AlCl3As a catalyst, the electric heating jacket is heated to 90 ℃, and the reaction is carried out for 12 hours under the magnetic stirring and reflux. After the thin layer chromatography tracking is carried out until the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained mixture is separated and purified by silica gel column chromatography and dried to obtain 88.89mg of the target compound with the total yield of 35.7 percent.
1H-NMR (300MHz,DMSO-d 6) δ (ppm): 10.53(1H,s), 7.35~7.75(5H,m), 7.62~7.85（5H,m）, 7.21（1H,m）, 7.02（1H,m）, 6.58（1H,m）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):198.5, 188.5, 152.7, 142.9, 137.9, 134.5, 130.3, 128.8, 128.6, 128.5, 127.9, 127.7, 125.8, 122.2, 119.7, 114.9, 100.5, 92; MS (ESI) for (M+H)+: 388.1。
Example 6
Preparation of (6-methyl-3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) (phenyl) methanone (corresponding to the product synthesized in the following reaction scheme).
128.8mg (0.8mmol) of 5-methyl-isatin and 215.1mg (0.96mmol) of 1, 3-diphenyl-1, 3-propanedione are charged into the reactor, 50mL1, 2-dichloroethane and 5mL DMF are added as reaction solvent, 13.7mg KMnO are added4、8.2 mg MnO2And 20mg of strong acid ion resin D001 as a catalyst, heating the mixture to 100 ℃ by an electric heating sleeve, and carrying out reflux reaction for 8 hours under magnetic stirring. After the completion of the reaction by thin layer chromatography, the solvent was distilled off under reduced pressure, and the cake was washed with 1, 2-dichloroethane and dried to obtain 86.8mg of the objective compound in a total yield of 29.5%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.85(1H,s), 7.33~7.77（5H,m）, 7.58~7.89（5H,m）, 7.11（1H,m）, 6.72（1H,s）, 6.52（1H,d）, 2.34（3H,m）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):172.5, 168.5, 153.2, 145.2, 138.9, 135.5, 134.8, 130.3, 129.9， 128.8, 128.5, 127.5, 126.3, 120.9, 111.5, 99.8, 93.0, 22.7; MS (ESI) for (M+Na)+:390.1。
Example 7
Preparation of 1- (6-fluoro-3-methyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized in the following reaction scheme).
165mg (1 mmol) of 5-fluoro-isatin and 120.1mg (1.2mmol) of 2, 4-pentanedione were charged into a reactor, 50mL of tetrahydrofuran and 5mL of DMF were added as a reaction solvent, and 1mL of H was added2O2And 20mg of strong acid ion resin D001 as a catalyst, heating the mixture to 75 ℃ by an electric heating sleeve, and carrying out reflux reaction for 12 hours by magnetic stirring. Tracing to reverse by thin layer chromatographyAfter completion of the reaction, the solvent was distilled off under reduced pressure, and the cake was washed with tetrahydrofuran and dried to obtain 156.9mg of the objective compound in a total yield of 63.5%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.54 (1H, s), 6.89(1H,d), 6.75(1H,d)， 6.54(1H,s), 2.27(3H,s), 2.15(3H,s); 13C-NMR (75MHz, DMSO-d 6) δ (ppm):166.5，165.1, 155.6, 152.8, 138.9, 126.3, 115.2, 108.2, 106.7, 95.1, 22.8, 10.7; MS (ESI) for (M+H)+:248.1。
Example 8
Preparation of 1- (7-chloro-3-methyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized in the following reaction scheme).
153.8mg (0.85mmol) of 6-chloro-isatin and 102.1mg (1.02mmol) of 2, 4-pentanedione were charged into a reactor, 50mL of toluene and 5mL of DMF were added as reaction solvents, and 13.6mg of KMnO was added4、7.5mg MnO2And 20mg of strong acid ion resin D001 as a catalyst, heating the mixture to 115 ℃ by an electric heating sleeve, and carrying out reflux reaction for 9 hours by magnetic stirring. After the thin layer chromatography was followed until the reaction was completed, the solvent was distilled off under reduced pressure, and the filter cake was washed with toluene and dried to obtain 127.2mg of the objective compound with a total yield of 56.9%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.87(1H,s), 7.21(1H,d), 6.85(1H,s)， 6.73(1H,d)， 2.28（3H,s）, 2.23（3H,s）; 13C-NMR (75MHz, DMSO-d 6) δ (ppm):165.5, 164.1, 153.5, 136.8, 128.4, 126.3, 121.3, 115.9, 106.3, 92.5, 23.9, 11.8; MS (ESI) for (M+Na)+:286.0。
Example 9
Preparation of 1- (8-fluoro-3-methyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) ethanone (corresponding to the product synthesized in the following reaction scheme).
198mg (1.2mmol) of 7-fluoro-isatin and 144.1mg (1.44mmol) of 2, 4-pentanedione were charged into the reactor, 50mL of tetrahydrofuran and 5mL of DMF were added as a reaction solvent, and 1mL of H was added2O2And 14.5mg ZnCl2As a catalyst, the electric heating jacket is heated to 85 ℃, and the reaction is carried out for 12 hours under the magnetic stirring and reflux. After the thin layer chromatography is tracked until the reaction is completed, the solvent is evaporated under reduced pressure, and a filter cake is washed by tetrahydrofuran and dried to obtain 175.5mg of the target compound with the total yield of 59.2%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.95 (1H, s), 7.59（1H,d）, 6.89（1H,d）， 6.75(1H,t),2.38(3H,s), 2.24(3H,s); 13C-NMR (75MHz, DMSO-d 6) δ (ppm):164.2，161.1, 153.6, 148.8, 129.9, 126.3, 117.4, 109.9, 106.3, 92.5, 23.9, 11.2; MS (ESI) for (M+H)+:248.1。
Example 10
Preparation of (6-fluoro-3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) (phenyl) methanone (corresponding to the product synthesized in the following reaction scheme).
115.5mg (0.7mmol) of 5-fluoro-isatin and 188.2mg (0.84mmol) of 1, 3-diphenyl-1, 3-propanedione are charged into the reactor, 50mL of dichloroethane and 5mL of DMF are added as reaction solvent, 1mL of H are added2O2And catalytic amount of strong acid ion resin D001 as catalyst, heating to 100 deg.c with electric heating jacket, and reflux reaction under magnetic stirring for 9.5 hr. After the thin layer chromatography tracking is carried out until the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained mixture is separated and purified by silica gel column chromatography and dried to obtain the target compound of 152.2mg with the total yield of 58.6%.
1H-NMR(300MHz,DMSO-d 6)δ(ppm):10.68(1H,s),7.62~7.91(5H,m),7.33~7.78(5H,m), 6.89(1H,d), 6.75(1H,s), 6.69(1H,s); 13C-NMR (75MHz, DMSO-d 6) δ (ppm):170.5, 169.7, 157.6, 138.5, 137.9, 134.5, 131.3, 129.5, 128.6, 127.8, 115.1, 109.8, 100.8, 92.1; MS (ESI) for (M+Na)+:394.1。
Example 11
Preparation of (7-chloro-3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) (phenyl) methanone (corresponding to the product synthesized in the following reaction scheme).
117.6mg (0.65mmol) of 6-chloro-isatin and 174.8mg (0.78mmol) of 1, 3-diphenyl-1, 3-propanedione are charged into the reactor, 50mL of tetrahydrofuran and 5mL of DMF are added as reaction solvent, 1mL of H are added2O2And 14.7mg AlCl3As a catalyst, the electric heating jacket is heated to 70 ℃, and the reaction is carried out for 12 hours under the magnetic stirring and reflux. After the thin layer chromatography is traced to complete reaction, the solvent is evaporated under reduced pressure, the obtained mixture is separated and purified by silica gel column chromatography, and the target compound 64.1mg is obtained after drying, and the total yield is 21.5%.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.76(1H, s), 7.65~7.89(5H,m), 7.23~7.82(5H,m),7.25(1H，d),6.95(1H,s),6.81(1H,d); 13C-NMR (75MHz, DMSO-d 6) δ (ppm):174.8, 169.5, 152.3, 137.9, 136.8, 134.5, 131.3, 129.2, 128.8, 128.5, 128.2, 127.8, 125.2, 121.3, 119.5, 111.9, 100.7, 92.5; MS (ESI) for (M+H)+:388.1。
Example 12
Preparation of (8-fluoro-3-phenyl-9H- [1,2] dioxino [3,4-b ] indol-4-yl) (phenyl) methanon (corresponding to the product synthesized by the following reaction scheme).
132mg (0.8mmol) of 7-fluoro-isatin and 215.1mg (0.96mmol) of 1, 3-diphenyl-1, 3-propanedione are introduced into the reactor, 50mL of toluene and 5mL of DMF are added as reaction solvent, 1mL of H are added2O2And catalytic amount of strong acid ion resin D001 as catalyst, heating to 110 deg.c with electric jacket, and magnetically stirring to reflux for 8.5 hr. After the thin layer chromatography is tracked until the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained mixture is separated and purified by silica gel column chromatography and dried to obtain 190.6mg of the target compound with the total yield of 64.2 percent.
1H-NMR (300MHz, DMSO-d 6) δ (ppm): 10.89(1H,s), 7.68~7.85(5H,m),7.22~7.67(5H,m), 7.14(1H,d), 6.85(1H,d),6.75(1H,t); 13C-NMR (75MHz, DMSO-d 6) δ (ppm):169.2, 167.5, 153.2, 148.9, 136.5, 134.5, 132.7, 130.3, 129.2, 128.8, 127.9, 122.1, 118.4, 108.5, 100.9, 93.3; MS (ESI) for (M+Na)+: 394.1。
Example 13 bacteriostatic Activity testing of Compounds of the invention
The compound of the invention is tested by bacteriostatic activity test, and the bacteriostatic efficacy is determined by a bacteriostatic circle method.
Test strains and culture media: enteropathogenic escherichia coli (EPEC), enterotoxigenic escherichia coli (ETEC), enteroinvasive escherichia coli (EIEC), enterohemorrhagic escherichia coli (EHEC); beef extract peptone culture medium.
Preparation of test strains: inoculating test strains to corresponding test tube slant culture media in a sterile room, inoculating a plurality of strains for each strain, culturing in a constant-temperature incubator (bacteria: 37 ℃, 24 hours; fungi: 28 ℃, 48 hours), and refrigerating at 0-4 ℃ for later use; secondly, respectively using inoculating loops to pick a little of thallus in a test tube filled with 9mL of sterile water, oscillating uniformly to prepare a thallus suspension, and adjusting the concentration of the thallus suspension to ensure that the thallus content is 106-107 cfu.mL-1Thus obtaining the test strain suspension.
And (3) determining the antibacterial efficacy: and (3) determining the bacteriostatic activity by taking a corresponding solvent dimethyl sulfoxide (DMSO) as a negative control, and expressing the bacteriostatic activity by using the diameter of a bacteriostatic zone.
The test results are detailed in table 1, wherein the sample refers to the isatin mother nucleus peroxy compound prepared in the corresponding example, and the sample number corresponds to the specific number of the compound obtained in the preparation example.
Compounds a to l correspond to the compounds synthesized in examples 1 to 12.
The compound a shows good bacteriostatic activity in 4 bacteria tested, and the compound b and c times also show good bacteriostatic activity in different cell strains. The experimental results show that the compound has good bacteriostatic activity and can be used as an antibacterial drug for further preclinical research.
Claims (7)
1. A compound represented by the structural formula a-l,
2. a process for the preparation of a compound according to claim 1, characterized in that:
R1selected from hydrogen, F, Cl or methyl, R2Selected from methyl or phenyl, said R1And R2The substituents correspond to the compounds of claim 1;
taking isatin or a derivative A thereof and a dicarbonyl compound B as raw materials, and synthesizing in an organic solvent under the action of a catalyst to obtain a compound shown in a structural general formula (I);
the catalyst is an oxidant anda combination of acidic substances, the oxidizing agent being selected from KMnO4/MnO2、O3、H2O2The acidic substance is selected from AlCl3、ZnCl2Macroporous strong-acid styrene ion resin;
the organic solvent is selected from toluene, carbon tetrachloride and 1, 2-dichloroethane.
3. The method of synthesis according to claim 2, characterized by comprising the steps of:
(1) the molar ratio of the isatin or the derivative A thereof to the dicarbonyl compound B is 1 (1-1.2), adding an organic solvent, adding DMF (1/5-1/20 volume of the organic solvent), adding a catalytic amount of catalyst, and carrying out reflux reaction at 80-120 ℃;
(2) and tracking the reaction to be complete by a thin-layer chromatography method, stopping heating, evaporating the solid-liquid mixture of the reaction system under reduced pressure to remove the solvent, cooling to room temperature, filtering, washing the filter cake with an organic solvent to obtain a crude product of the isatin mother nucleus peroxide, and further recrystallizing to obtain the target product.
4. The method of synthesizing isatin mother nucleus peroxy compound according to claim 3, wherein: the organic solvent is toluene.
5. The method of synthesizing isatin mother nucleus peroxy compound according to claim 3, wherein: the catalyst is H2O2And a strongly acidic ionic resin D001.
6. The method of synthesizing isatin mother nucleus peroxy compound according to claim 3, wherein: the reaction temperature is 90-120 ℃, and the reaction time is 6-12 hours.
7. Use of a compound according to claim 1 for the preparation of an in vitro bacteriostatic agent.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN201810285272.9A CN108558895B (en) | 2018-04-03 | 2018-04-03 | Isatin mother nucleus peroxide compound with antibacterial activity and preparation method thereof |
| JP2018225263A JP6618599B2 (en) | 2018-04-03 | 2018-11-30 | Isatin peroxo compound having antibacterial activity and method for preparing the same |
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| CN201810285272.9A CN108558895B (en) | 2018-04-03 | 2018-04-03 | Isatin mother nucleus peroxide compound with antibacterial activity and preparation method thereof |
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| CN108558895A CN108558895A (en) | 2018-09-21 |
| CN108558895B true CN108558895B (en) | 2021-04-06 |
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