CN117069644A - Novel 2-methylindoline antitumor compound and preparation method and application thereof - Google Patents

Novel 2-methylindoline antitumor compound and preparation method and application thereof Download PDF

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CN117069644A
CN117069644A CN202311021490.9A CN202311021490A CN117069644A CN 117069644 A CN117069644 A CN 117069644A CN 202311021490 A CN202311021490 A CN 202311021490A CN 117069644 A CN117069644 A CN 117069644A
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ethyl acetate
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methylindoline
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CN117069644B (en
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付冬君
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Beijing University of Chinese Medicine
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    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

The application discloses a novel 2-methylindoline antitumor compound, a preparation method and application thereof, belonging to the field of medicinesDomain. The application adopts a simple and efficient synthesis method to prepare the antitumor drug with a novel structure. The structural formula is as follows:

Description

Novel 2-methylindoline antitumor compound and preparation method and application thereof
Technical Field
The application belongs to the field of medicines, and particularly relates to a novel 2-methylindoline antitumor compound and a preparation method and application thereof.
Background
Cancer is a significant public health problem worldwide. The cancer patient is not only subjected to a heavy economic burden, but also is psychologically afflicted. In global cancers, the incidence of gastric cancer is at position 5 and mortality is at position 4. Prostate cancer is one of the most common malignancies in the male genitourinary system. According to global cancer incidence and mortality statistics by the international cancer research institute in 2020, prostate cancer incidence and mortality are at the 2 nd and 5 th positions of male solid malignant tumors, respectively. Liver cancer is malignancy with worldwide morbidity rank 6. In recent years, treatment means for liver cancer have been developed, but the recurrence rate of liver cancer is still at a high level. Research shows that the recurrence and transfer rate of liver cancer patients reaches 40% -70% within 5 years after operation. The development of novel broad-spectrum antitumor drugs capable of treating gastric cancer, prostatic cancer and liver cancer has important clinical significance for treating malignant tumors.
Indoline (english name Indoline) also known as 2, 3-Indoline (2, 3-dihydrooindole); 2,3-dihydro-1H-indole (2, 3-dihydro-1H-indole); IDN for short; indoline is colorless to yellow transparent liquid at normal temperature and normal pressure, is flammable, has a stimulating effect on eyes and skin, and is harmful to human bodies. Slightly soluble in water and stable. The chemical formula is C8H9N. The indoline is mainly used for synthesizing derivative products of indoles, such as indoline dyes and sensitizers of solar cells, and has good photoelectric conversion performance. It is also an intermediate of medicine and plant growth regulator. In recent years, the study shows that the small molecule compound containing the indoline fragment has potential anti-tumor activity. However, no related medicine and no simple synthesis method exist at present.
Disclosure of Invention
In order to solve the problems, the application provides a novel 2-methylindoline compound, which has the following structural formula:wherein R1 and R2 substituent segments->Included
Further, the novel compounds include:
the application also provides a preparation method of the novel 2-methylindoline compound, which specifically comprises the following steps: 2-methylindoline A and chloroacetyl chloride B are dissolved in methylene dichloride, and react for a plurality of times at a proper temperature under alkaline conditions; extracting with water for 2-4 times, extracting with saturated saline water for 2-4 times, and drying with anhydrous sodium sulfate for 10-14 hr; suction filtration and concentration of organic layer to prepare intermediate C; adding carbon disulfide and secondary amine containing different substituents into an organic solvent, and reacting for a plurality of times at a proper temperature under an alkaline condition; suction filtering, concentrating under reduced pressure to dry, and adding ethyl acetate for complete dissolution; extracting ethyl acetate organic layer with water for three times, extracting with saturated saline water for three times, drying with desiccant for 10-14 hr, and eluting with column chromatography to obtain compounds D1-D12 with novel structures; the eluent is ethyl acetate and petroleum ether.
Further, the organic solvent comprises at least one of methanol, ethanol, n-propanol, isopropanol, n-butanol, dichloromethane, chloroform, toluene, 1, 4-dioxane, acetone, tetrahydrofuran, acetonitrile and ethyl acetate.
Further, the alkaline condition has a pH of 8 to 13.
Further, the desiccant for the reaction is any one or two of anhydrous sodium sulfate, anhydrous magnesium sulfate, silica gel and molecular sieve.
Further, the reaction temperature is 0-60 ℃ and the reaction time is 5-16h.
Further, the eluent comprises ethyl acetate and petroleum ether in the following proportion: ethyl acetate/petroleum ether=8/1-12/1.
The application discloses application of the compound in preparing antitumor drugs.
The application also provides an anti-tumor pharmaceutical composition, which takes the compound as an active ingredient; the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.
The application has the following beneficial effects:
the application synthesizes a class of 2-methylindoline compounds with novel structures by adopting simple and efficient reaction, and the total yield of the target compound D-D12 prepared from the intermediate C reaches more than 70%. The in-vitro anti-tumor activity test of the compound discovers that the novel structure 2-methylindoline compound has obvious inhibition effect on the growth of human gastric cancer cells MGC803, human prostatic cancer cells 22RV1 and human liver cancer cells HePG2, and the novel structure 2-methylindoline compound can be used as a lead compound or a candidate compound for the development of anti-tumor drugs.
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In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows a compound (D8) 13 C-NMR chart.
Detailed Description
Various exemplary embodiments of the application will now be described in detail, which should not be considered as limiting the application, but rather as more detailed descriptions of certain aspects, features and embodiments of the application.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the application. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the application described herein without departing from the scope or spirit of the application. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present application. The specification and examples of the present application are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
The technical scheme of the application is conventional in the field, and the reagents or raw materials are purchased from commercial sources or are disclosed.
Example 1
1. Preparation of Compound (D1)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under alkaline conditions potassium ethoxide (7.2 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To ethanol (20 ml), which is an organic solvent, was added carbon disulfide (7.2 mmol) and piperidine (7.2 mmol), and the mixture was reacted at 80℃for 10 hours under alkaline condition pyridine (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous magnesium sulfate for 12 hours, and eluted by column chromatography to give compound D1 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 11:1, yield 75.8%.
2. Preparation of Compound (D2)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted at 40℃for 10 hours under basic conditions of calcium hydroxide (3.6 mmol). Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To isopropyl alcohol (20 ml), which is an organic solvent, was added carbon disulfide (7.2 mmol) and 1-phenylpiperazine (7.2 mmol), and the mixture was reacted at 85℃for 9 hours under basic conditions of triethylamine (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D2 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, 71.3% yield.
3. Preparation of Compound (D3)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in methylene chloride (15 ml), and reacted under alkaline conditions of potassium hydrogencarbonate (7.2 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To toluene (20 ml), which is an organic solvent, was added carbon disulfide (7.2 mmol) and 3-methylpiperidine (7.2 mmol), and the mixture was reacted at 100℃for 6 hours under alkaline conditions of sodium phosphate (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over silica gel for 12 hours, and eluted by column chromatography to prepare the novel structural compound D3. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 11:1, yield 78.2%.
4. Preparation of Compound (D4)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under basic conditions with potassium hydroxide (7.2 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To tetrahydrofuran (20 ml), which is an organic solvent, carbon disulfide (7.2 mmol) and 2, 6-dimethylpiperidine (7.2 mmol) were added, and the mixture was reacted under alkaline conditions with sodium phosphate dodecahydrate (7.2 mmol) at 66℃for 12 hours. Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, and the molecular sieve was dried for 12 hours, and eluted by column chromatography to prepare compound D4 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, yield 70.8%.
5. Preparation of Compound (D5)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted for 10 hours at 40℃under basic conditions sodium methoxide (7.2 mmol). Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To n-butanol (20 ml), which is an organic solvent, were added carbon disulfide (7.2 mmol) and 3, 5-dimethylpiperidine (7.2 mmol), and the mixture was reacted at 120℃for 6 hours under alkaline condition pyridine (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous magnesium sulfate for 12 hours, and eluted by column chromatography to give compound D5 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, yield 76.9%.
6. Preparation of Compound (D6)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under basic conditions potassium carbonate (3.6 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To organic solvent 1, 4-dioxane (20 ml) was added carbon disulfide (7.2 mmol) and benzimidazole (7.2 mmol), and the mixture was reacted at 100℃for 5 hours under alkaline condition sodium hydroxide (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D6 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 10:1, 71.3% yield.
7. Preparation of Compound (D7)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under basic conditions sodium methoxide (3.6 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To acetone (20 ml), which is an organic solvent, were added carbon disulfide (7.2 mmol) and 1- (4-tert-butylbenzyl) piperazine (7.2 mmol), and the mixture was reacted under alkaline conditions with potassium hydrogencarbonate (7.2 mmol) at 60℃for 10 hours. Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D7 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, yield 80.5%.
8. Preparation of Compound (D8)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under basic conditions triethylamine (3.6 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To acetonitrile (20 ml), which is an organic solvent, were added carbon disulfide (7.2 mmol) and 1- (4-methoxyphenyl) piperazine (7.2 mmol), and the mixture was reacted at 85℃for 10 hours under alkaline conditions of sodium hydrogencarbonate (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D8 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 11:1, 86.2% yield.
9. Preparation of Compound (D9)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted under alkaline conditions potassium ethoxide (3.6 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To organic solvent 1, 4-dioxane (20 ml), carbon disulfide (7.2 mmol) and 1-methylpiperazine (7.2 mmol) were added, and the mixture was reacted at 100℃for 6 hours under alkaline conditions of sodium phosphate dodecahydrate (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D9 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, yield 82.9%.
10. Preparation of Compound (D10)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in methylene chloride (15 ml), and reacted under alkaline conditions of potassium hydrogencarbonate (7.2 mmol) at 40℃for 10 hours. Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To n-propanol (20 ml) as an organic solvent, carbon disulfide (7.2 mmol) and 2-methylindoline (7.2 mmol) were added, and the mixture was reacted at 100℃for 7 hours under alkaline conditions of potassium t-butoxide (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D10 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 12:1, yield 76.3%.
11. Preparation of Compound (D11)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted for 10 hours at 40℃under basic conditions sodium methoxide (7.2 mmol). Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To methanol (20 ml), which is an organic solvent, were added carbon disulfide (7.2 mmol) and morpholine (7.2 mmol), and the mixture was reacted at 65℃for 12 hours under alkaline conditions of potassium ethoxide (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D11 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 10:1, yield 70.9%.
12. Preparation of Compound (D12)
2-methylindoline A (6 mmol) and chloroacetyl chloride B (7.2 mmol) were dissolved in dichloromethane (15 ml) and reacted at 40℃for 10 hours under basic conditions of calcium hydroxide (3.6 mmol). Water was added to extract 3 times (15 ml each time), saturated brine was added to extract 3 times (15 ml each time), and the mixture was dried over anhydrous sodium sulfate for 12 hours. Suction filtration and concentration of the organic layer to prepare intermediate C. To dichloromethane (20 ml), which is an organic solvent, were added carbon disulfide (7.2 mmol) and 1- (2-pyridyl) piperazine (7.2 mmol), and the mixture was reacted at 25℃for 16 hours under alkaline condition sodium hydroxide (7.2 mmol). Suction filtration, vacuum concentration to dryness, adding ethyl acetate to dissolve completely. The ethyl acetate organic layer was extracted three times (15 ml each time) with water, extracted three times (15 ml each time) with saturated brine, dried over anhydrous sodium sulfate for 12 hours, and eluted by column chromatography to give compound D12 of novel structure. The eluent is ethyl acetate and petroleum ether. The eluent is ethyl acetate: petroleum ether = 11:1, yield 78.6%.
Antitumor Activity assay of the compound of example 2:
a sample of 1-2 mg of the compound was weighed into an EP tube, and then prepared into a 10mM solution using biological grade dimethyl sulfoxide, and stored at 4 ℃. The logarithmic growth phase human gastric cancer cell MGC803, the human prostatic cancer cell 22RV1 and the human liver cancer cell HePG2 are inoculated into a 96-well plate, after 24 hours of culture, the culture medium is discarded, and the compound is diluted to 10 mu M by the culture medium and added into the 96-well plate. After the medicine acts for 48 hours, 20 mu L of MTT is added into each hole, after the culture is continued for 4 hours, liquid is sucked, 100 mu L of biological grade dimethyl sulfoxide is added, the vibration is uniform, the absorbance value is detected at 490nm of an enzyme-labeling instrument, and the cell survival rate is calculated. The antitumor drug 5-fluorouracil (5-Fu) is used as a reference substance, and the experimental results are shown in Table 1.
TABLE 1 tumor cell survival
From table 1, it can be seen that the novel 2-methylindoline compounds (D1, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11 and D12) have obvious anti-tumor growth inhibition effects on human gastric cancer cells MGC803, human prostatic cancer cells 22RV1 and human liver cancer cells HePG2, which indicates that the compounds can be used as candidate or lead compounds for further development and applied to preparation of anti-tumor drugs.
The above embodiments are only illustrative of the preferred embodiments of the present application and are not intended to limit the scope of the present application, and various modifications and improvements made by those skilled in the art to the technical solutions of the present application should fall within the protection scope defined by the claims of the present application without departing from the design spirit of the present application.

Claims (10)

1. A novel 2-methylindoline compound is characterized in that,the structural formula is as follows:wherein R1 and R2 substituent segments->Comprises->
2. A novel 2-methylindoline compound according to claim 1, characterized in that it comprises:
。
3. a process for the preparation of a novel 2-methylindoline compound according to any one of claims 1 to 2, comprising the steps of: 2-methylindoline A and chloroacetyl chloride B are dissolved in methylene dichloride, and react for a plurality of times at a proper temperature under alkaline conditions; extracting with water for 2-4 times, extracting with saturated saline water for 2-4 times, and drying with anhydrous sodium sulfate for 10-14 hr; suction filtration and concentration of organic layer to prepare intermediate C; adding carbon disulfide and secondary amine containing different substituents into an organic solvent, and reacting for a plurality of times at a proper temperature under an alkaline condition; suction filtering, concentrating under reduced pressure to dry, and adding ethyl acetate for complete dissolution; extracting ethyl acetate organic layer with water for three times, extracting with saturated saline water for three times, drying with desiccant for 10-14 hr, and eluting with column chromatography to obtain compounds D1-D12 with novel structures; the eluent is ethyl acetate and petroleum ether.
4. The method according to claim 3, wherein the organic solvent comprises at least one of methanol, ethanol, n-propanol, isopropanol, n-butanol, dichloromethane, chloroform, toluene, 1, 4-dioxane, acetone, tetrahydrofuran, acetonitrile, and ethyl acetate.
5. A method of preparation according to claim 3, wherein the alkaline conditions have a pH of 8-13.
6. The method according to claim 3, wherein the drying agent is any one or two of anhydrous sodium sulfate, anhydrous magnesium sulfate, silica gel, and molecular sieve.
7. A process according to claim 3, wherein the reaction temperature is 0-60 ℃ and the reaction time is 5-16h.
8. The method according to claim 3, wherein the ratio of ethyl acetate to petroleum ether in the eluent is: ethyl acetate/petroleum ether=8/1-12/1.
9. Use of a class of compounds according to claim 1 or 2 for the preparation of an antitumor drug.
10. An antitumor pharmaceutical composition characterized in that the pharmaceutical composition comprises the compound according to claim 1 or 2 as an active ingredient; the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.
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