CN107759475A - Dehydroabietylamine derivatives and its preparation method and application - Google Patents
Dehydroabietylamine derivatives and its preparation method and application Download PDFInfo
- Publication number
- CN107759475A CN107759475A CN201711099452.XA CN201711099452A CN107759475A CN 107759475 A CN107759475 A CN 107759475A CN 201711099452 A CN201711099452 A CN 201711099452A CN 107759475 A CN107759475 A CN 107759475A
- Authority
- CN
- China
- Prior art keywords
- dehydroabietylamine
- mixture
- structural formula
- derivatives
- dehydroabietylamine derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/31—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by at least three rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/60—Preparation of compounds containing amino groups bound to a carbon skeleton by condensation or addition reactions, e.g. Mannich reaction, addition of ammonia or amines to alkenes or to alkynes or addition of compounds containing an active hydrogen atom to Schiff's bases, quinone imines, or aziranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of dehydroabietylamine derivatives and its preparation method and application.The structural formula of the dehydroabietylamine derivatives is any one in following structural formula：The present invention has drawn from natural prodcuts, and raw materials used to be easy to get, be cheap, compound synthesis method is simple, and synthesis gained compound anticancer effect is good.
Description
Technical field
The present invention relates to dehydroabietylamine derivatives technical field, it is more particularly related to which a kind of dehydroabietylamine spreads out
Biology and its preparation method and application.
Background technology
Rosin is a kind of natural products obtained using pine tree as Raw material processing, and resource is more, and price is low, and purposes is wide.It is being changed
Learn chemical industry to play a significant role, mainly for the manufacture of products such as soap, paper, paint, rubber.With the hair of scientific research
Open up, the biochemical property of dehydroabietylamine and its derivative is gradually found by researchers, dehydroabietylamine derivatives conduct
One of branch, the enthusiasm of scientific research people is greatly evoked.Current research finds that dehydroabietylamine derivatives are shown extensively
General biological activity, including antibacterial, antimycotic, desinsection, weeding and active anticancer.
Cancer threatened human health life for a long time, although treatment of the modern medicine for tumour occurred it is more
Kind method such as chemotherapy, radiotherapy, operative treatment and optical dynamic therapy etc., these treatment methods have effect to a certain extent
Meanwhile patient can be also allowed by unthinkable pain or generation allergic reaction etc..The Major Clinical treatment means of cancer at present
For surgery excision and chemotherapy, wherein, chemotherapy gives numerous cancer patients family due to its expensive medical fee
Bring huge financial burden in front yard.Therefore, it is that the chemotherapeutics that cancer patients find high performance cheap is an extremely important section
Grind work.
The content of the invention
It is an object of the invention to solve at least the above, and provide the advantages of at least will be described later.
It is (1), (2), the dehydroabietylamine derivatives of (3) and its system it is a still further object of the present invention to provide a kind of structural formula
Preparation Method and application.
In order to realize according to object of the present invention and further advantage, there is provided a kind of dehydroabietylamine derivatives, it is described
The structural formula of dehydroabietylamine derivatives is any one in following structural formula：
Preferably, described structural formula is the method for the dehydroabietylamine derivatives of (1), is comprised the following steps：A1：By quality
The dehydroabietylamine that number is 1.3-1.5 is mixed with the valeraldehyde that mass fraction is 350-370 and ambient temperature overnight, obtains mixture 1；
A2：Mixture 1 described in ice bath, and it is 520-600 sodium borohydrides to add mass fraction thereto, obtains mixture 2；A3：By A2
After the mixture 2 that step obtains is stirred at room temperature overnight, it is evaporated under reduced pressure and removes solvent, obtain mixture 3；A4：To A3 steps
Distilled water is added in obtained mixture 3, extracts and collects organic phase 1, by the anhydrous sodium sulfate drying of organic phase 1, crosses and filters out
Solvent is removed, purifies to obtain the dehydroabietylamine derivatives that structural formula is (1) by column chromatography.
Preferably, in step A4, the organic solvent of extraction process is using ethyl acetate.
Preferably, described structural formula is the method for the dehydroabietylamine derivatives of (2), is comprised the following steps：B1：By quality
The dehydroabietylamine that number is 1.3-1.5 mixes with the isobutylaldehyde that mass fraction is 350-370 and ambient temperature overnight obtains mixture 4；
B2：Mixture 4 described in ice bath, and the sodium borohydride that mass fraction is 520-600 is added thereto, obtain mixture 5；B3：Will
After the mixture 5 that B2 steps obtain is stirred at room temperature overnight, it is evaporated under reduced pressure removing solvent and obtains mixture 6；B4：By B3 steps
After adding distilled water in obtained mixture 6, extract and collect organic phase 2, by the anhydrous sodium sulfate drying of organic phase 2, filtering
After removing solvent, purify to obtain the dehydroabietylamine derivatives that structural formula is (2) by column chromatography.
Preferably, described structural formula is the method for the dehydroabietylamine derivatives of (3), is comprised the following steps：C1：By dehydrogenation
Abietyl amine is mixed to get mixture 7 with absolute methanol, and the quality of dehydroabietylamine and the volume ratio of absolute methanol are 1.3-1.5g：35-
45mL；C2：The 1- methyl isophthalic acid H- imidazoles -2- first that mass fraction is 500-580 is added dropwise into the mixture 7 through C1 step process
Aldehyde, mixture 3 is obtained, mixture 3 is stored at room temperature 24h；C3：The solvent in the mixture 3 through C2 step process is removed, is added
After deionized water, extract and collect organic phase 3, by the anhydrous sodium sulfate drying of organic phase 3, filtering, be evaporated under reduced pressure and remove solvent,
The dehydroabietylamine derivatives that structural formula is (3) are obtained by pillar layer separation；
Wherein, step C2 and C3 is carried out under argon gas protection.
Preferably, the organic solvent that extraction process uses is dichloromethane.
Preferably, during the chromatography, the mobile phase used is the mixture of petroleum ether and ethyl acetate, and
The volume ratio of the two is petroleum ether：Ethyl acetate=4:1.
Preferably, during the chromatography, the mobile phase used is the mixture of petroleum ether and ethyl acetate, and
The volume ratio of the two is petroleum ether：Ethyl acetate=10:1.
Preferably, during the chromatography, the mobile phase used is ethyl acetate.
Application of the described dehydroabietylamine derivatives in cancer therapy drug is prepared.
The present invention comprises at least following beneficial effect：
Compared with the prior art, the dehydroabietylamine derivatives of offer of the invention, the cancer cell common to 6 kinds are respectively provided with poison
Property, and toxicity is stronger, and new direction is provided for the preparation of cancer therapy drug.And dehydroabietylamine derivatives provided by the invention
Preparation method is simple, yield is high, preparation method is raw materials used to be easy to get, is cheap.
Further advantage, target and the feature of the present invention embodies part by following explanation, and part will also be by this
The research and practice of invention and be understood by the person skilled in the art.
Brief description of the drawings
Fig. 1 is that the dehydroabietylamine derivatives that structural formula of the present invention is (1) act on the toxotest figure of 6 kinds of cancer cells；
Fig. 2 is that the dehydroabietylamine derivatives that structural formula of the present invention is (2) act on the toxotest figure of 6 kinds of cancer cells；
Fig. 3 is that the dehydroabietylamine derivatives that structural formula of the present invention is (3) act on the toxotest figure of 6 kinds of cancer cells；
Fig. 4 is the nuclear magnetic resonance H spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (1)；
Fig. 5 is the nuclear magnetic resonance C spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (1)；
Fig. 6 is the nuclear magnetic resonance H spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (2)；
Fig. 7 is the nuclear magnetic resonance C spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (2)；
Fig. 8 is the nuclear magnetic resonance H spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (3)；
Fig. 9 is the nuclear magnetic resonance C spectrograms for the dehydroabietylamine derivatives that structural formula of the present invention is (3)；
Figure 10 is the IC50 values that structural formula of the present invention acts on 6 kinds of cancer cells for (1), (2), the dehydroabietylamine of (3)
Summary view.
Embodiment
The present invention is described in further detail below in conjunction with the accompanying drawings, to make those skilled in the art with reference to specification text
Word can be implemented according to this.
It should be noted that experimental method described in following embodiments, is conventional method unless otherwise specified, institute
Reagent and material are stated, unless otherwise specified, is commercially obtained.
As Figure 1-10 shows, the present invention provides a kind of dehydroabietylamine derivatives, the structural formula of the dehydroabietylamine derivatives
It is any one in following structural formula：
Described structural formula is the method for the dehydroabietylamine derivatives of (1), is comprised the following steps：A1：It is by mass fraction
1.3-1.5 dehydroabietylamine is mixed with the valeraldehyde that mass fraction is 350-370 and ambient temperature overnight, obtains mixture 1；A2：Ice
The mixture 1 is bathed, and it is 520-600 sodium borohydrides to add mass fraction thereto, obtains mixture 2；A3：A2 steps are obtained
To mixture 2 be stirred at room temperature overnight after, be evaporated under reduced pressure remove solvent, obtain mixture 3；A4：Obtained to A3 steps
Distilled water is added in mixture 3, extracts and collects organic phase 1, by the anhydrous sodium sulfate drying of organic phase 1, be filtered to remove solvent,
Purify to obtain the dehydroabietylamine derivatives that structural formula is (1) by column chromatography.
In step A4, the organic solvent of extraction process is using ethyl acetate.
Described structural formula is the method for the dehydroabietylamine derivatives of (2), is comprised the following steps：B1：It is by mass fraction
1.3-1.5 dehydroabietylamine is mixed with the isobutylaldehyde that mass fraction is 350-370 and ambient temperature overnight obtains mixture 4；B2：Ice bath
The mixture 4, and the sodium borohydride that mass fraction is 520-600 is added thereto, obtain mixture 5；B3：B2 steps are obtained
To mixture 5 be stirred at room temperature overnight after, be evaporated under reduced pressure remove solvent obtain mixture 6；B4：B3 steps are obtained mixed
After adding distilled water in compound 6, extract and collect organic phase 2, by the anhydrous sodium sulfate drying of organic phase 2, be filtered to remove solvent
Afterwards, purify to obtain the dehydroabietylamine derivatives that structural formula is (2) by column chromatography.
Described structural formula is the method for the dehydroabietylamine derivatives of (3), is comprised the following steps：C1：By dehydroabietylamine with
Absolute methanol is mixed to get mixture 7, and the quality of dehydroabietylamine and the volume ratio of absolute methanol are 1.3-1.5g：35-45mL；
C2：The 1- methyl isophthalic acid H- imidazoles -2- formaldehyde that mass fraction is 500-580 is added dropwise into the mixture 7 through C1 step process, obtains
Mixture 3, mixture 3 is stored at room temperature 24h；C3：The solvent in the mixture 3 through C2 step process is removed, adds deionization
After water, extract and collect organic phase 3, by the anhydrous sodium sulfate drying of organic phase 3, filtering, be evaporated under reduced pressure and remove solvent, pass through post
Chromatographic isolation obtains the dehydroabietylamine derivatives that structural formula is (3)；
Wherein, step C2 and C3 is carried out under argon gas protection, the quality of dehydroabietylamine and 1- methyl isophthalic acid H- imidazoles -2- formaldehyde
Portion rate is 1.3-1.5：500-580.
The organic solvent that extraction process uses is dichloromethane.
During the chromatography, the mobile phase used is the mixture of petroleum ether and ethyl acetate, and the two
Volume ratio is petroleum ether：Ethyl acetate=4:1.
During the chromatography, the mobile phase used is the mixture of petroleum ether and ethyl acetate, and the two
Volume ratio is petroleum ether：Ethyl acetate=10:1.
During the chromatography, the mobile phase used is ethyl acetate.
Application of the described dehydroabietylamine derivatives in cancer therapy drug is prepared.
With reference to embodiment, the present invention will be described,
First, preparation structure formula is as follows for the embodiment of the method for the dehydroabietylamine derivatives of (1)：
Embodiment 1：The valeraldehyde for weighing 1.3mg dehydroabietylamines and 350mg is added in clean 250mL round-bottomed flasks,
Room temperature reaction overnight, 520mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction knot
Shu Hou, it is evaporated under reduced pressure and removes solvent, add a small amount of distilled water, be extracted with ethyl acetate, collects organic phase, done with anhydrous sodium sulfate
It is dry, filtering, solvent is removed, passes through column chromatography (petroleum ether：Ethyl acetate=4:1) isolated structural formula is the dehydrogenation fir of (1)
Amine derivative.
Embodiment 2：The valeraldehyde for weighing 1.425mg dehydroabietylamines and 321mg is added in clean 250mL round bottoms burning,
Room temperature reaction overnight, 570mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction knot
Shu Hou, it is evaporated under reduced pressure and removes solvent, add a small amount of distilled water, be extracted with ethyl acetate, collects organic phase, done with anhydrous sodium sulfate
It is dry, filtering, solvent is removed, passes through column chromatography (petroleum ether：Ethyl acetate=4:1) isolated structural formula is the dehydrogenation fir of (1)
Amine derivative.
Embodiment 3：The valeraldehyde for weighing 1.5mg dehydroabietylamines and 370mg is added in clean 250mL round-bottomed flasks,
Room temperature reaction overnight, 600mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction knot
Shu Hou, it is evaporated under reduced pressure and removes solvent, add a small amount of distilled water, be extracted with ethyl acetate, collects organic phase, done with anhydrous sodium sulfate
It is dry, filtering, solvent is removed, passes through column chromatography (petroleum ether：Ethyl acetate=4:1) isolated structural formula is the dehydrogenation fir of (1)
Amine derivative.
Wherein, embodiment 2, the colorless oil chemical combination that the structural formula prepared is 1.78g for the dehydroabietylamine derivatives of (1)
Thing, yield 67%.
The result of nuclear magnetic resonance as illustrated in figures 4-5, and is analyzed as follows：1H NMR(400MHz,CDCl3):δ 7.22 (d, J=
8.1Hz, 1H), 7.03 (d, J=8.0Hz, 1H), 6.93 (s, 1H), 2.99-2.81 (m, 3H), 2.60 (t, J=7.1Hz, 2H),
2.54 (d, J=11.7Hz, 1H), 2.36-2.27 (m, 2H), 1.86-1.59 (m, 6H), 1.44 (t, J=12.2Hz, 5H),
1.38-1.29 (m, 4H), 1.26 (d, J=7.1Hz, 9H), 0.95 (d, J=4.2Hz, 3H), 0.92 (d, J=7.0Hz, 3H)；13C NMR(101MHz,CDCl3):δ147.61,145.39,134.85,126.78,124.34,123.78,61.89,51.12,
45.49,38.53,37.44,36.93,36.25,33.47,30.39,29.90,29.61,25.41,24.04,22.69,
19.32,18.86 (d, J=12.4Hz), 14.17.Prove, compound manufactured in the present embodiment is structural formula taking off for (1) really
Hydrogen abietyl amine derivative.
2nd, preparation structure formula is as follows for the embodiment of the method for the dehydroabietylamine derivatives of (2)：
Embodiment 4：The isobutylaldehyde for weighing 1.3mg dehydroabietylamines and 350mg is added in clean 250mL round-bottomed flasks,
Room temperature reaction overnight, 520mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction knot
Shu Hou, it is evaporated under reduced pressure and removes solvent, adds a small amount of distilled water and the extraction of a small amount of dichloromethane, collect organic phase, use anhydrous slufuric acid
Sodium is dried, and filtering, is removed solvent, is passed through column chromatography (petroleum ether：Ethyl acetate=10:1) isolated structural formula is the de- of (2)
Hydrogen abietyl amine derivative.
Embodiment 5：The isobutylaldehyde for weighing 1.425mg dehydroabietylamines and 361mg is added to clean 250mL round-bottomed flasks
In, room temperature reaction overnight, 570mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction
After end, it is evaporated under reduced pressure and removes solvent, adds a small amount of distilled water and the extraction of a small amount of dichloromethane, organic phase is collected, with anhydrous sulphur
Sour sodium is dried, and filtering, is removed solvent, is passed through column chromatography (petroleum ether：Ethyl acetate=10:1) isolated structural formula is (2)
Dehydroabietylamine derivatives.
Embodiment 6：The isobutylaldehyde for weighing 1.5mg dehydroabietylamines and 370mg is added in clean 250mL round-bottomed flasks,
Room temperature reaction overnight, 600mg sodium borohydrides is then slowly added under condition of ice bath, continue to be stirred overnight at room temperature.Reaction knot
Shu Hou, it is evaporated under reduced pressure and removes solvent, adds a small amount of distilled water and the extraction of a small amount of dichloromethane, collect organic phase, use anhydrous slufuric acid
Sodium is dried, and filtering, is removed solvent, is passed through column chromatography (petroleum ether：Ethyl acetate=10:1) isolated structural formula is the de- of (2)
Hydrogen abietyl amine derivative.
Embodiment 5, the faint yellow solid that the structural formula prepared is 1.14g for the dehydroabietylamine derivatives of (2), yield are
67%.
The result of nuclear magnetic resonance as shown in fig. 6-7, and is analyzed as follows：1H NMR(400MHz,CDCl3):δ 7.21 (d, J=
8.2Hz, 1H), 7.02 (dd, J=8.1,1.5Hz, 1H), 6.92 (s, 1H), 2.87 (dt, J=13.8,6.4Hz, 3H), 2.53
(d, J=11.8Hz, 1H), 2.40 (dd, J=6.8,2.0Hz, 2H), 2.29 (t, J=10.5Hz, 2H), 1.82-1.64 (m,
7H), 1.42 (t, J=13.4Hz, 3H), 1.26 (s, 3H), 1.25 (s, 6H), 0.94 (s, 3H), 0.92 (d, J=0.9Hz,
3H), 0.90 (d, J=0.9Hz, 3H)；13C NMR(101MHz,CDCl3):δ147.60,145.36,134.87,126.78,
124.36,123.77,61.75,59.16,45.32,38.52,37.44,37.01,36.20,33.44,30.44,28.10,
(25.46,24.02,20.67 d, J=3.3Hz), 19.39,18.85 (d, J=16.4Hz).Prove, manufactured in the present embodimentization
Compound is the dehydroabietylamine derivatives that structural formula is (2) really.
3rd, preparation structure formula is as follows for the embodiment of the method for the dehydroabietylamine derivatives of (3)：
Embodiment 7：Under argon gas protection, 1.3g dehydroabietylamines are sequentially added into 250mL round-bottomed flasks and 35mL is anhydrous
Methanol, 500mg 1- methyl isophthalic acid H- imidazoles -2- formaldehyde is then slowly added dropwise, is placed in and reacts 24h at room temperature.Supervised through column chromatography chromatogram
Solvent is removed after surveying reaction completely, adds 30mL deionized waters, is once extracted with (3 × 60mL) dichloromethane, after stratification
Collect dichloromethane layer and remove solvent with anhydrous sodium sulfate drying, filtering, vacuum distillation, pass through column chromatography (ethyl acetate) point
From obtain structural formula be (3) dehydroabietylamine derivatives.
Embodiment 8：Argon gas protection under, sequentially added into 250mL round-bottomed flasks 1.425g dehydroabietylamines and 40mL without
Water methanol, 550mg 1- methyl isophthalic acid H- imidazoles -2- formaldehyde is then slowly added dropwise, is placed in and reacts 24h at room temperature.Through column chromatography chromatogram
Solvent is removed after monitoring reaction completely, adds 30mL deionized waters, is once extracted with (3 × 60mL) dichloromethane, stratification
Dichloromethane layer is collected afterwards and is removed solvent with anhydrous sodium sulfate drying, filtering, vacuum distillation, is passed through column chromatography (ethyl acetate)
Isolated structural formula is the dehydroabietylamine derivatives of (3).
Embodiment 9：Under argon gas protection, 1.5g dehydroabietylamines are sequentially added into 250mL round-bottomed flasks and 40mL is anhydrous
Methanol, 580mg 1- methyl isophthalic acid H- imidazoles -2- formaldehyde is then slowly added dropwise, is placed in and reacts 24h at room temperature.Supervised through column chromatography chromatogram
Solvent is removed after surveying reaction completely, adds 30mL deionized waters, is once extracted with (3 × 60mL) dichloromethane, after stratification
Collect dichloromethane layer and remove solvent with anhydrous sodium sulfate drying, filtering, vacuum distillation, pass through column chromatography (ethyl acetate) point
From obtain structural formula be (3) dehydroabietylamine derivatives.
Wherein, embodiment 8, the pale yellow oil that the structural formula prepared is 1.43g for the dehydroabietylamine derivatives of (3)
Compound, yield 76%.
The result of nuclear magnetic resonance as Figure 8-9, and is analyzed as follows：1H NMR(400MHz,CDCl3):δ8.29(s,1H),
7.18 (d, J=8.1Hz, 1H), 7.08 (s, 1H), 6.98 (d, J=8.0Hz, 1H), 6.87 (d, J=2.8Hz, 2H), 3.92
(s, 3H), 3.47 (d, J=12.2Hz, 1H), 3.36 (d, J=12.1Hz, 1H), 2.92-2.71 (m, 3H), 2.28 (d, J=
12.7Hz,1H),1.93-1.50(m,6H),1.48-1.31(m,2H),1.25-1.19(m,9H),1.03(s,3H)；13C NMR
(101MHz,CDCl3):δ153.08,147.30,145.37,143.29,134.82,128.94,126.84,124.67,
124.34,123.77,73.52,45.71,38.49,37.92,37.59,36.60,35.57,33.36,30.44,25.56,
23.95 (d, J=3.4Hz), 19.51,18.76 (d, J=19.3Hz).Prove, compound manufactured in the present embodiment is really knot
Structure formula is the dehydroabietylamine derivatives of (3).
4th, detection of the present invention to the toxicity of 6 kinds of cancer cells, prove by the following technical programs：
When described dehydroabietylamine derivatives are used to treat cancer cell, concrete operation step is：Prepared with complete medium
The dehydroabietylamine derivatives of various concentrations, incubated cell is after 24 hours, with MTT colorimetric determination cancer cell relative survival rates.
Described cancer cell is estrogen receptor positive cervical cancer cell Hela, estrogen receptor positive breast cancer cell
MCF-7, estrogen receptor negative breast cancer cell MDA-MB-231, androgen receptor positive prostate cell LNCaP, androgen
Receptor negative prostatic cell PC-3 and Gastric cancer cell MKN45.
Described dehydroabietylamine derivatives are configured to dehydroabietylamine derivatives mass concentration with the pure DMSO of analysis in advance
20mg/mL DMSO solution, the low concentration solution of different gradients is then diluted to complete medium, DMSO contains in final solution
Amount is no more than 1%.
The diluted compounds mass concentration that is used for is that the complete medium used in 20mg/mL DMSO solution is：It is corresponding
It is containing 10% hyclone, 1% penicillin and chain to test complete medium used when cancer cell is Hela cells and MKN45 cells
The RPMI-1640 culture mediums of mycin；Corresponding experiment cancer cell is used when being MCF-7, MDA-MB-231, LNCaP and PC-3 cell
Complete medium is the DMEM culture mediums containing 10% hyclone, 1% penicillin and streptomysin.
The sample quality concentration of the dehydroabietylamine derivatives is 0-200 μ g/mL.
It is 490nm that described mtt assay, which detects absorbing wavelength selected during cancer cell relative survival rate,.
Structural formula is (1), (2), (3) dehydroabietylamine derivatives to the toxotest tests concrete steps of 6 kinds of cancer cells such as
Under, wherein, every kind of derivative to the experiment of the toxotest of every kind of cancer cell at least three times more than, in test data, every kind of derivative
The survival rate that thing acts on every kind of cancer cell is average value：
(1), structural formula is tested the toxotest of 6 kinds of cancer cells for the dehydroabietylamine derivatives of (1)：
1st, structural formula is prepared for the dehydroabietylamine derivatives storing solution of (1)
Weigh 20mg structural formulas be (1) dehydroabietylamine derivatives be dissolved in 1mL DMSO solvents, be configured to be containing structural formula
(1) dehydroabietylamine derivatives are 20mg/mL DMSO solution.
2nd, MTT preliminary experiments
With complete medium, by structural formula in above-mentioned (1), for the dehydroabietylamine derivatives storing solution of (1), to be diluted to quality dense
Degree is followed successively by 0,5,10,20,50,100,200 μ g/mL solution (wherein, when experimental cell is Hela cells and MKN45 cells
Shi Suoyong complete mediums are the RPMI-1640 culture mediums containing 10% hyclone, 1% penicillin and streptomysin；Corresponding experiment
Cancer cell when being MCF-7, MDA-MB-231, LNCaP and PC-3 cell complete medium used be containing 10% hyclone 1%
The DMEM culture mediums of penicillin and streptomysin), old culture medium is discarded after cell attachment, is used matched somebody with somebody solution instead and is continued to be incubated 24h, adds
Enter after MTT with the absorbance at ELIASA detection 490nm places, calculate versus cell survival rate, obtain dehydrogenation fir of the structural formula for (1)
Sphere of action of the amine derivative to 6 kinds of cancer cells used in experiment.
3rd, IC50 values detect
The killing of different cancer cells is acted on for the dehydroabietylamine derivatives of (1) according to above-mentioned steps (2) resulting structures formula
Rate close to 50% concentration reconfigure structural formula containing various concentrations be (1) dehydroabietylamine derivatives complete medium it is molten
Liquid.The concentration for wherein acting on the dehydroabietylamine derivatives that Hela eucaryotic cell structures formula is (1) is 0,5,10,12,14,16,18,
20、22μg/mL；The structural formula for acting on MKN45 cells is that the concentration of the dehydroabietylamine derivatives of (1) is 0,10,20,30,40 μ
g/mL；The concentration for acting on the dehydroabietylamine derivatives that MCF-7 eucaryotic cell structures formula is (1) is 0,5,10,15,20,22,25 μ g/
mL；The concentration for acting on the dehydroabietylamine derivatives that MDA-MB-231 eucaryotic cell structures formula is (1) is 0,5,10,15,18,20,22,
25、28、30μg/mL；The structural formula for acting on LNCaP cells be the concentration of the dehydroabietylamine derivatives of (1) be 0,5,10,15,
20、22、25、28、30μg/mL；The structural formula for acting on PC-3 cells be the concentration of the dehydroabietylamine derivatives of (1) be 0,5,
10、20、22、25、28、30μg/mL.Old culture medium is discarded after cell attachment, matched somebody with somebody solution is used instead and continues to be incubated 24h, add MTT
Afterwards with the absorbance at ELIASA detection 490nm, versus cell survival rate is calculated, and calculate IC50 values.
As a result as shown in figure 1, the IC50 value scopes that structural formula acts on 6 kinds of cancer cells for the dehydroabietylamine derivatives of (1) are
20~40 μ g/mL.Wherein, the IC50 values for acting on Hela cells are 20.8 μ g/mL, and the IC50 values for acting on MKN45 cells are
37.3 μ g/mL, the IC50 values for acting on MCF-7 cells are 23.1 μ g/mL, and the IC50 values for acting on MDA-MB-231 cells are
26.9 μ g/mL, the IC50 values for acting on LNCaP cells are 31.5 μ g/mL, and the IC50 values for acting on PC-3 cells are 25.1 μ g/
mL。
Specific test data is as shown in the table：
Table 1 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the statistical form of the toxicity of MCF-7 cells
| Concentration (ug/mL) | MCF-7 cell survival rates |
| 0 | 100 |
| 5 | 96.0911 |
| 10 | 95.97458 |
| 15 | 90.92956 |
| 20 | 83.72617 |
| 22 | 57.93609 |
| 25 | 25.83686 |
Table 2 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the system of the toxicity of MDA-MB-231 cells
Count table
Table 3 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the statistical form of the toxicity of Hela cells
| Concentration (ug/mL) | Hela cell survival rates |
| 0 | 100 |
| 5 | 87.08306 |
| 10 | 80.59526 |
| 12 | 73.9996 |
| 14 | 67.67832 |
| 16 | 62.59365 |
| 18 | 58.07785 |
| 20 | 51.78506 |
| 22 | 43.37659 |
Table 4 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the statistical form of the toxicity of MKN45 cells
| Concentration (ug/mL) | MKN45 cell survival rates |
| 0 | 100 |
| 10 | 99.62739 |
| 20 | 90.50895 |
| 30 | 72.88094 |
| 40 | 40.03701 |
Table 5 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the statistical form of the toxicity of PC-3 cells
Table 6 be various concentrations structural formula for (1) dehydroabietylamine derivatives to the statistical form of the toxicity of LNCaP cells
| Concentration (ug/mL) | LNCaP cell survival rates |
| 0 | 100 |
| 5 | 93.79876 |
| 10 | 86.90629 |
| 15 | 83.46796 |
| 20 | 78.32527 |
| 22 | 74.37543 |
| 25 | 70.04246 |
| 28 | 60.41276 |
| 30 | 51.43873 |
(2), structural formula is tested the toxotest of 6 kinds of cancer cells for the dehydroabietylamine derivatives of (2)：
1st, structural formula is prepared for the dehydroabietylamine derivatives storing solution of (2)
Weigh 20mg structural formulas be (2) dehydroabietylamine derivatives be dissolved in 1mL DMSO solvents, be configured to be containing structural formula
(2) dehydroabietylamine derivatives are 20mg/mL DMSO solution.
2nd, MTT preliminary experiments
With complete medium, by structural formula in above-mentioned (1), for the dehydroabietylamine derivatives storing solution of (2), to be diluted to quality dense
Degree is followed successively by 0,5,10,20,50,100,200 μ g/mL solution (wherein, when experimental cell is Hela cells and MKN45 cells
Shi Suoyong complete mediums are the RPMI-1640 culture mediums containing 10% hyclone, 1% penicillin and streptomysin；Corresponding experiment
Cancer cell when being MCF-7, MDA-MB-231, LNCaP and PC-3 cell complete medium used be containing 10% hyclone 1%
The DMEM culture mediums of penicillin and streptomysin), old culture medium is discarded after cell attachment, is used matched somebody with somebody solution instead and is continued to be incubated 24h, adds
Enter after MTT with the absorbance at ELIASA detection 490nm places, calculate versus cell survival rate, obtain dehydrogenation fir of the structural formula for (2)
Amine derivative to the killing rates of 6 kinds of cancer cells used in experiment close to 50% concentration.
3rd, IC50 values detect
The killing of different cancer cells is acted on for the dehydroabietylamine derivatives of (2) according to above-mentioned steps (2) resulting structures formula
Rate close to 50% concentration reconfigure structural formula containing various concentrations be (2) dehydroabietylamine derivatives complete medium it is molten
Liquid.The concentration for wherein acting on the dehydroabietylamine derivatives that Hela eucaryotic cell structures formula is (2) is 0,5,10,15,18,20,22,
25、28、30μg/mL；The structural formula for acting on MKN45 cells be the concentration of the dehydroabietylamine derivatives of (2) be 0,5,10,20,
25、30、35、40、45μg/mL；The concentration for acting on the dehydroabietylamine derivatives that MCF-7 eucaryotic cell structures formula is (2) is 0,5,10,
15、18、20、22、25、28μg/mL；Act on the concentration for the dehydroabietylamine derivatives that MDA-MB-231 eucaryotic cell structures formula is (2)
For 0,5,10,15,18,20,22,25,28,30 μ g/mL；The structural formula for acting on LNCaP cells derives for the dehydroabietylamine of (2)
The concentration of thing is 0,10,20,25,30,32,35,38 μ g/mL；The structural formula for acting on PC-3 cells spreads out for the dehydroabietylamine of (2)
The concentration of biology is 0,10,20,25,30,32,35,38,40 μ g/mL.Old culture medium is discarded after cell attachment, is used instead matched somebody with somebody molten
Liquid continues to be incubated 24h, adds after MTT with the absorbance at ELIASA detection 490nm places, calculating versus cell survival rate, and calculates
IC50 values.
As a result as shown in Fig. 2 the IC50 value scopes that structural formula acts on 6 kinds of cancer cells for the dehydroabietylamine derivatives of (2) are
20~40 μ g/mL.Wherein, the IC50 values for acting on Hela cells are 23.9 μ g/mL, and the IC50 values for acting on MKN45 cells are
33.6 μ g/mL, the IC50 values for acting on MCF-7 cells are 22.1 μ g/mL, and the IC50 values for acting on MDA-MB-231 cells are
29.1 μ g/mL, the IC50 values for acting on LNCaP cells are 26.5 μ g/mL, and the IC50 values for acting on PC-3 cells are 32.7 μ g/
mL。
Specific test data is as shown in the table：
Table 7 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the statistical form of the toxicity of MCF-7 cells
Table 8 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the system of the toxicity of MDA-MB-231 cells
Count table
| Concentration (ug/mL) | MDA-MB-231 cell survival rates |
| 0 | 100 |
| 5 | 96.93076 |
| 10 | 93.58494 |
| 15 | 90.3551 |
| 18 | 87.8444 |
| 20 | 85.84939 |
| 22 | 80.71616 |
| 25 | 68.21556 |
| 28 | 55.38187 |
| 30 | 46.1694 |
Table 9 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the statistical form of the toxicity of Hela cells
Table 10 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the statistical form of the toxicity of MKN45 cells
| Concentration (ug/mL) | MKN45 cell survival rates |
| 0 | 100 |
| 5 | 98.67184 |
| 10 | 93.34979 |
| 20 | 89.98002 |
| 25 | 83.56135 |
| 30 | 72.42595 |
| 35 | 34.685 |
| 40 | 11.09838 |
| 45 | 1.07898 |
Table 11 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the statistical form of the toxicity of PC-3 cells
| Concentration (ug/mL) | PC-3 cell survival rates |
| 0 | 100 |
| 10 | 99.10079 |
| 20 | 99.37265 |
| 25 | 82.18319 |
| 30 | 63.60309 |
| 32 | 54.39147 |
| 35 | 38.09076 |
| 38 | 29.01506 |
| 40 | 20.40987 |
Table 12 be various concentrations structural formula for (2) dehydroabietylamine derivatives to the statistical form of the toxicity of LNCaP cells
| Concentration (ug/mL) | LNCaP cell survival rates |
| 0 | 100 |
| 10 | 95.15085 |
| 20 | 83.05398 |
| 25 | 59.13189 |
| 30 | 39.38273 |
| 32 | 21.19986 |
| 35 | 7.109 |
| 38 | 2.41013 |
(3), structural formula is tested the toxotest of 6 kinds of cancer cells for the dehydroabietylamine derivatives of (3)：
1st, structural formula is prepared for the dehydroabietylamine derivatives storing solution of (3)
Weigh 20mg structural formulas be (3) dehydroabietylamine derivatives be dissolved in 1mL DMSO solvents, be configured to be containing structural formula
(3) dehydroabietylamine derivatives are 20mg/mL DMSO solution.
2nd, MTT preliminary experiments
With complete medium, by structural formula in above-mentioned (1), for the dehydroabietylamine derivatives storing solution of (3), to be diluted to quality dense
Degree is followed successively by 0,5,10,20,50,100,200 μ g/mL solution (wherein, when experimental cell is Hela cells and MKN45 cells
Shi Suoyong complete mediums are the RPMI-1640 culture mediums containing 10% hyclone, 1% penicillin and streptomysin；Corresponding experiment
Cancer cell when being MCF-7, MDA-MB-231, LNCaP and PC-3 cell complete medium used be containing 10% hyclone 1%
The DMEM culture mediums of penicillin and streptomysin), old culture medium is discarded after cell attachment, is used matched somebody with somebody solution instead and is continued to be incubated 24h, adds
Enter after MTT with the absorbance at ELIASA detection 490nm places, calculate versus cell survival rate, obtain dehydrogenation fir of the structural formula for (3)
Amine derivative to the killing rates of 6 kinds of cancer cells used in experiment close to 50% concentration.
3rd, IC50 values detect
The killing of different cancer cells is acted on for the dehydroabietylamine derivatives of (3) according to above-mentioned steps (2) resulting structures formula
Rate close to 50% concentration reconfigure structural formula containing various concentrations be (3) dehydroabietylamine derivatives complete medium it is molten
Liquid.The concentration for wherein acting on the dehydroabietylamine derivatives that Hela eucaryotic cell structures formula is (3) is 0,2,3,4,5,6,7,8 μ g/mL；
The structural formula for acting on MKN45 cells is that the concentration of the dehydroabietylamine derivatives of (3) is 0,5,10,12,14,16,18 μ g/mL；
The concentration for acting on the dehydroabietylamine derivatives that MCF-7 eucaryotic cell structures formula is (3) is 0,2,4,6,7,8 μ g/mL；Act on MDA-
MB-231 eucaryotic cell structures formula is that the concentration of the dehydroabietylamine derivatives of (3) is 0,2,4,6,7,8,9,10,11,12 μ g/mL；Effect
In the concentration for the dehydroabietylamine derivatives that the structural formula of LNCaP cells is (3) be 0,2,3,4,5,6,7 μ g/mL；Act on PC-3
The structural formula of cell is that the concentration of the dehydroabietylamine derivatives of (3) is 0,2,4,6,7,8,9,10,11 μ g/mL.After cell attachment
Discard old culture medium, use instead matched somebody with somebody solution continue be incubated 24h, add MTT after with ELIASA detection 490nm place absorbance, count
Versus cell survival rate is calculated, and calculates IC50 values.
As a result as shown in figure 3, structural formula acts on variety classes cancer cell for the dehydroabietylamine derivatives of (3), to 6 kinds of cancers
Cell all has preferable fragmentation effect, and except MKN45 is extracellular, the IC50 values for acting on other cells are below 10 μ g/mL.Its
In, the IC50 values for acting on Hela cells are 5.2 μ g/mL, and the IC50 values for acting on MKN45 cells are 13.9 μ g/mL, are acted on
The IC50 values of MCF-7 cells are 6.3 μ g/mL, and the IC50 values for acting on MDA-MB-231 cells are 8.3 μ g/mL, are acted on
The IC50 values of LNCaP cells are 5.4 μ g/mL, and the IC50 values for acting on PC-3 cells are 8.1 μ g/mL.
Table 13 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the statistical form of the toxicity of MCF-7 cells
| Concentration (ug/mL) | MCF-7 cell survival rates |
| 0 | 100 |
| 2 | 95.7324 |
| 4 | 87.03979 |
| 6 | 61.04066 |
| 7 | 24.77919 |
| 8 | 16.47573 |
Table 14 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the system of the toxicity of MDA-MB-231 cells
Count table
Table 15 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the statistical form of the toxicity of Hela cells
| Concentration (ug/mL) | Hela cell survival rates |
| 0 | 100 |
| 2 | 94.94533 |
| 3 | 96.07564 |
| 4 | 80.91692 |
| 5 | 46.96562 |
| 6 | 36.15909 |
| 7 | 17.79961 |
| 8 | 2.25004 |
Table 16 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the statistical form of the toxicity of MKN45 cells
| Concentration (ug/mL) | MKN45 cell survival rates |
| 0 | 100 |
| 5 | 95.61764 |
| 10 | 82.62665 |
| 12 | 68.87647 |
| 14 | 51.74232 |
| 16 | 23.62503 |
| 18 | 5.43985 |
Table 17 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the statistical form of the toxicity of PC-3 cells
Table 18 be various concentrations structural formula for (3) dehydroabietylamine derivatives to the statistical form of the toxicity of LNCaP cells
| Concentration (ug/mL) | LNCaP cell survival rates |
| 0 | 100 |
| 2 | 93.77132 |
| 3 | 85.81662 |
| 4 | 80.94556 |
| 5 | 58.09114 |
| 6 | 33.01269 |
| 7 | 8.42202 |
Structural formula is (1), (2), the dehydroabietylamine derivatives of (3) act on the IC50 values of 6 kinds of cancer cells as shown in Figure 10,
Representative structure formula is the dehydroabietylamine derivatives of (1), and representative structure formula is the dehydroabietylamine derivatives of (2), and representative structure formula is
(3) dehydroabietylamine derivatives.As seen from the figure, structural formula be (1), (2), that the dehydroabietylamine derivatives of (3) act on 6 kinds of cancers is thin
The IC50 values of born of the same parents are not high, illustrate structural formula for (1), (2), (3) dehydroabietylamine derivatives to the killing abilities of 6 kinds of cancer cells
By force.
Although embodiment of the present invention is disclosed as above, it is not restricted in specification and embodiment listed
With it can be applied to various suitable the field of the invention completely, can be easily for those skilled in the art
Other modification is realized, therefore under the universal limited without departing substantially from claim and equivalency range, it is of the invention and unlimited
In specific details and shown here as the legend with description.
Claims (10)
1. a kind of dehydroabietylamine derivatives, it is characterised in that the structural formula of the dehydroabietylamine derivatives is in following structural formula
Any one：
2. the method that one kind prepares the dehydroabietylamine derivatives that structural formula as claimed in claim 1 is (1), it is characterised in that
Comprise the following steps：
A1：The dehydroabietylamine that mass fraction is 1.3-1.5 is mixed to simultaneously room temperature mistake with the valeraldehyde that mass fraction is 350-370
At night, obtain mixture 1；
A2：Mixture 1 described in ice bath, and it is 520-600 sodium borohydrides to add mass fraction thereto, obtains mixture 2；
A3：After the mixture 2 that A2 steps obtain is stirred at room temperature overnight, it is evaporated under reduced pressure and removes solvent, obtain mixture 3；
A4：Distilled water is added in the mixture 3 obtained to A3 steps, extracts and collects organic phase 1, by organic phase 1 with anhydrous sulphur
Sour sodium is dried, and is filtered to remove solvent, purifies to obtain the dehydroabietylamine derivatives that structural formula is (1) by column chromatography.
3. preparation structure formula as claimed in claim 2 is the method for the dehydroabietylamine derivatives of (1), it is characterised in that step
In A4, the organic solvent of extraction process is ethyl acetate.
4. the method that one kind prepares the dehydroabietylamine derivatives that structural formula as claimed in claim 1 is (2), it is characterised in that
Comprise the following steps：
B1：The dehydroabietylamine that mass fraction is 1.3-1.5 is mixed to simultaneously ambient temperature overnight with the isobutylaldehyde that mass fraction is 350-370
Obtain mixture 4；
B2：Mixture 4 described in ice bath, and the sodium borohydride that mass fraction is 520-600 is added thereto, obtain mixture 5；
B3：After the mixture 5 that B2 steps obtain is stirred at room temperature overnight, it is evaporated under reduced pressure removing solvent and obtains mixture 6；
B4：After adding distilled water in the mixture 6 that B3 steps are obtained, extract and collect organic phase 2, by organic phase 2 with anhydrous
Sodium sulphate is dried, and after being filtered to remove solvent, purifies to obtain the dehydroabietylamine derivatives that structural formula is (2) by column chromatography.
5. the method that one kind prepares the dehydroabietylamine derivatives that structural formula as claimed in claim 1 is (3), it is characterised in that
Comprise the following steps：
C1：Dehydroabietylamine and absolute methanol are mixed to get mixture 7, the quality of dehydroabietylamine and the volume ratio of absolute methanol are
1.3-1.5g：35-45mL；
C2：The 1- methyl isophthalic acid H- imidazoles -2- formaldehyde that mass fraction is 500-580 is added dropwise into the mixture 7 through C1 step process,
Mixture 3 is obtained, mixture 3 is stored at room temperature 24h；
C3：The solvent in the mixture 3 through C2 step process is removed, after adding deionized water, extracts and collects organic phase 3, will
The anhydrous sodium sulfate drying of organic phase 3, filtering, it is evaporated under reduced pressure and removes solvent, structural formula is obtained as (3) by pillar layer separation
Dehydroabietylamine derivatives；
Wherein, step C2 and C3 is carried out under argon gas protection.
6. the method for preparing dehydroabietylamine derivatives as described in claim 4 or 5, the organic solvent that extraction process uses is two
Chloromethanes.
7. preparation structure formula as claimed in claim 2 is the method for (1) dehydroabietylamine derivatives, it is characterised in that the color
Compose in post purge process, the mobile phase used is petroleum ether and the mixture of ethyl acetate, and the volume ratio of the two is petroleum ether：
Ethyl acetate=4:1.
8. preparation structure formula as claimed in claim 4 is the method for (2) dehydroabietylamine derivatives, it is characterised in that the color
Compose in post purge process, the mobile phase used is petroleum ether and the mixture of ethyl acetate, and the volume ratio of the two is petroleum ether：
Ethyl acetate=10:1.
9. preparation structure formula as claimed in claim 5 is the method for (3) dehydroabietylamine derivatives, it is characterised in that the color
Compose in post purge process, the mobile phase used is ethyl acetate.
10. application of the dehydroabietylamine derivatives described in claim 1 in cancer therapy drug is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711099452.XA CN107759475B (en) | 2017-11-09 | 2017-11-09 | Dehydroabietylamine derivative and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711099452.XA CN107759475B (en) | 2017-11-09 | 2017-11-09 | Dehydroabietylamine derivative and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107759475A true CN107759475A (en) | 2018-03-06 |
| CN107759475B CN107759475B (en) | 2020-09-22 |
Family
ID=61272285
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711099452.XA Active CN107759475B (en) | 2017-11-09 | 2017-11-09 | Dehydroabietylamine derivative and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107759475B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997149A (en) * | 2018-09-07 | 2018-12-14 | 嘉兴学院 | A kind of dehydroabietylamine derivatives and its preparation method and application that aryl replaces |
| CN112538027A (en) * | 2020-12-31 | 2021-03-23 | 江苏省中国科学院植物研究所 | Preparation and application of amide compound of ginkgolic acid |
| CN114315913A (en) * | 2022-01-17 | 2022-04-12 | 嘉兴学院 | Pt (II) complex with anti-tumor activity and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146341A (en) * | 2016-07-26 | 2016-11-23 | 南京林业大学 | A kind of salicylide dehydroabietylamine schiff base compound and its preparation method and application |
| CN106220570A (en) * | 2016-07-26 | 2016-12-14 | 南京林业大学 | Imidazoles dehydroabietylamine amides compound and its preparation method and application |
| CN106243042A (en) * | 2016-07-26 | 2016-12-21 | 南京林业大学 | Imidazoles dehydroabietylamine schiff base compounds and its preparation method and application |
| CN106316930A (en) * | 2016-07-26 | 2017-01-11 | 南京林业大学 | 3-methyl-2-pyridyl-dehydroabietylamine-Schiff base, preparation method and application thereof |
-
2017
- 2017-11-09 CN CN201711099452.XA patent/CN107759475B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146341A (en) * | 2016-07-26 | 2016-11-23 | 南京林业大学 | A kind of salicylide dehydroabietylamine schiff base compound and its preparation method and application |
| CN106220570A (en) * | 2016-07-26 | 2016-12-14 | 南京林业大学 | Imidazoles dehydroabietylamine amides compound and its preparation method and application |
| CN106243042A (en) * | 2016-07-26 | 2016-12-21 | 南京林业大学 | Imidazoles dehydroabietylamine schiff base compounds and its preparation method and application |
| CN106316930A (en) * | 2016-07-26 | 2017-01-11 | 南京林业大学 | 3-methyl-2-pyridyl-dehydroabietylamine-Schiff base, preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| TIINA LAAKSONEN 等: "Synthesis and applications of secondary amine derivatives of (+)-dehydroabietylamine in chiral molecular recognition", 《ORG. BIOMOL. CHEM》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997149A (en) * | 2018-09-07 | 2018-12-14 | 嘉兴学院 | A kind of dehydroabietylamine derivatives and its preparation method and application that aryl replaces |
| CN112538027A (en) * | 2020-12-31 | 2021-03-23 | 江苏省中国科学院植物研究所 | Preparation and application of amide compound of ginkgolic acid |
| CN112538027B (en) * | 2020-12-31 | 2022-08-26 | 江苏省中国科学院植物研究所 | Preparation and application of ginkgolic acid amide compound |
| CN114315913A (en) * | 2022-01-17 | 2022-04-12 | 嘉兴学院 | Pt (II) complex with anti-tumor activity and preparation method and application thereof |
| CN114315913B (en) * | 2022-01-17 | 2023-11-03 | 嘉兴学院 | Pt (II) complex with anti-tumor activity and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107759475B (en) | 2020-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108218927B (en) | Flavonoid glycoside compounds in Elaeagnus angustifolia flower and preparation method thereof | |
| CN105348192B (en) | Isoquinoline alkaloids bases compound of antiviral activity and preparation method thereof in a kind of wing pod Cassia tora | |
| CN106858710B (en) | A kind of benzisoxa furfuran compound that can improve cigarette smoking effect and preparation method and application | |
| CN107759475A (en) | Dehydroabietylamine derivatives and its preparation method and application | |
| CN106117138B (en) | A kind of isoquinoline alkaloids bases compound, preparation method and application with antibacterial activity | |
| Irungu et al. | Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica | |
| CN104761526B (en) | A kind of isoflavonoid with antiviral activity and its preparation method and application | |
| CN108892606A (en) | A kind of condensed-nuclei aromatics class compound and the preparation method and application thereof with antibacterial functions | |
| CN110483535A (en) | A kind of isoquinolin tricyclic alkaloid compound and its preparation method and application | |
| CN108774114A (en) | A kind of luxuriant and rich with fragrance class compound and the preparation method and application thereof in rush | |
| CN108358991A (en) | It is a kind of it is clear it is wide spend in triterpene compound and its preparation method and application | |
| CN108911953A (en) | A kind of luxuriant and rich with fragrance class compound and the preparation method and application thereof derived from natural plants | |
| CN105949065B (en) | A kind of sesquiterpenoids, its preparation method and its application in resisting tobacco mosaic virus drug is prepared | |
| CN109730359A (en) | Triterpene compound in a kind of adiantum cpilus-veneris and preparation method thereof and the application in electronic cigarette | |
| CN106146383B (en) | A kind of iso-indoles alkaloid compound, preparation method and application in tobacco | |
| CN109438545A (en) | A kind of natural antibacterial compound and preparation method thereof and the application in electronic cigarette | |
| CN107556325B (en) | The separation method of Alkaloid monomer in a kind of Diels Stephania Root | |
| CN102977059B (en) | Phenylpropanoid compound, and preparation method and application thereof | |
| CN106565654B (en) | A kind of novel flavone compound, Its Preparation Method And Use extracted from Bai Yun Shen | |
| CN102977065A (en) | Flavonoid compound and preparation method and application thereof | |
| CN105646151B (en) | A kind of purposes of acetylene compound and preparation method thereof and the compound | |
| CN109180471A (en) | Water cape jasmine monoterpenes compound crocusatinN and jasminosideB preparation method and application | |
| CN105503971B (en) | A kind of phytochemical, preparation method and application | |
| CN103896755A (en) | Chalcone compound and preparation method and application thereof | |
| CN115160335A (en) | Phthalide dimer and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |