CN105646432B - There is anti EB virus and anti-Kaposi's sarcoma associated herpesvirus action compound and its preparation method and application in hypericum japonicum - Google Patents
There is anti EB virus and anti-Kaposi's sarcoma associated herpesvirus action compound and its preparation method and application in hypericum japonicum Download PDFInfo
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- LREDFVBYDVVZAR-IRTUZJJPSA-N CC(C)C(C(C(C(C)(C)C1=C2C[C@@H](CCC(C)[C@H](CC(C)(C)/C=C/C3)O)[C@@]3(C)O1)O)=C2O)=O Chemical compound CC(C)C(C(C(C(C)(C)C1=C2C[C@@H](CCC(C)[C@H](CC(C)(C)/C=C/C3)O)[C@@]3(C)O1)O)=C2O)=O LREDFVBYDVVZAR-IRTUZJJPSA-N 0.000 description 1
- 0 CC(C)C(c(c(O)cc(*)c1C2)c1OC(C)(C)[C@@](CC1)[C@]2[C@]1(C)O)=O Chemical compound CC(C)C(c(c(O)cc(*)c1C2)c1OC(C)(C)[C@@](CC1)[C@]2[C@]1(C)O)=O 0.000 description 1
- OCGGASCBCJNUED-UPSGKMMVSA-N CC(C)C(c(c([O](C)=C)cc(OC)c1C[C@H](C(C)C(C)CC2)[C@@H]2C(C)(C)[O](C)=C)c1[O](C)=C)=O Chemical compound CC(C)C(c(c([O](C)=C)cc(OC)c1C[C@H](C(C)C(C)CC2)[C@@H]2C(C)(C)[O](C)=C)c1[O](C)=C)=O OCGGASCBCJNUED-UPSGKMMVSA-N 0.000 description 1
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- C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
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- C07D313/02—Seven-membered rings
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Abstract
The invention provides the compound with anti EB virus and anti-KSHV activity and its source, and isolation and purification method and application, specifically isolate and purify to obtain compound 1 18 from hypericum hypericum japonicum, compound 1 10 wherein is isolated and purified out from the hypericum japonicum of Hubei Province Qichun County Dabie Mountains Region collection in October, compound 11 18 is isolated and purified out from the hypericum japonicum of Lushan, Jiangxi city In The Lushan Area August part collection.Antiviral activity research is carried out to two kinds of tumorigenesis herpesvirals by this 18 compounds, it is found that compound 1, the DNA replication dna of 3,4,7 and 8 pairs of Epstein-Barr virus have inhibitory activity；3,6 and 13 17 pairs of Kaposi's sarcoma associated herpesvirus (KSHV) burst timeses of compound are replicated with inhibitory activity.
Description
Technical field
The invention belongs to pharmaceutical technology field, is related to anti EB virus and anti-Kaposi's sarcoma associated herpesvirus effect chemical combination
Compounds and its method for separating and preparing and application, and in particular to isolate and purify process, structural identification, antiviral and suppression virus
DNA replication dna effect etc..
Background technology
Epstein-Barr virus (Epstein-Barr virus, EBV) belongs to herpetoviridae Gammaherpesvirinae, is a kind of thermophilic people
Quasi-lymphocyte is viral, and about 95% health adult carries the virus in global range.EBV mainly hides in mankind's inactive state
Ripe bone-marrow-derived lymphocyte, be infectious mononucleosis pathogen, while with a variety of Human Lymphocytes and epithelium
The occurrence and development of cellularity tumour are relevant, such as nasopharyngeal carcinoma (nasopharyngeal carcinoma, NPC), Hodgkin's disease, T/
Bone-marrow-derived lymphocyte knurl of bone-marrow-derived lymphocyte knurl, Burkitt ' S lymthomas and immune deficiency patient etc., it is generally acknowledged DNA neoplastic diseases
Poison.Epstein-Barr virus is in the important stage that the DNA replication dna of burst times is that it breeds in cell, and therefore, screening and research and development are split for EBV
The medicine of the DNA replication dna of solution phase, have great importance for treatment EBV relevant diseases.
Kaposi's sarcoma associated herpesvirus (Kaposi ' s sarcoma associated herpesvirus, KSHV)
Also known as human herpesvirus 8,hhv 8 (Human herpesvirus 8, HHV-8), belongs to herpetoviridae (Herpesviridae),
It is a kind of double-stranded DNA (dsDNA) virus.KSHV is Kaposi's sarcoma (Kaposi ' s sarcoma, KS), primary effusion leaching
Bar knurl (Primary effusion lynphoma, PEL) and multicenter Calve disease (Multicentre cattleman ' s
Disease, MCD) pathogen, have higher KSHV infection rates and the KS incidences of disease in autonomous region of Xinjiang of China Uygur area.
The method of clinical treatment KSHV relevant diseases makes some progress at present, but these methods can not cure completely, and
And there is certain side effect to human body.Therefore, the medicine replicated for KSHV burst timeses is screened and researches and develops, for treating KSHV phases
Related disorders have great importance.
Hypericum japonicum (Hypericum japonicum) is Guttiferae Hypericum herbaceos perennial hypericum japonicum
The herb of [Hypericum japonicum (Thunb.) Herb], also known as hypericum japonicum, small Samson St Johswort, longleaf rabdosia stem, thousandweight building (Zhejiang
River) etc., originate in Liaoning, on the south Shandong to the Changjiang river each provinces and regions.It is among the people with all herbal medicine, have the effect of clearing heat and detoxicating, hemostasia and detumescence；
It is mainly used in treating catarrhal jaundice, rush down dysentery, child convulsion, infantile malnutrition due to digestive disturbances or intestinalparasites, tonsillitis, acute appendicitis, furuncle snake bite etc..In Europe, America
Among the people also have medicinal record.Modern pharmacological research shows that hypericum japonicum has antibacterial, liver protection, suppresses tumour and prevent and treat cardiovascular
Disease etc. acts on, and develops into injection and clinically treats acute hepatitis, chronic hepatitis.
The content of the invention：
The task of the present invention is to provide pure with the active compound of anti EB virus and anti-KSHV and its source and separation
Change methods and applications.
Realizing the concrete scheme of the present invention is：
Compound provided by the invention with anti EB virus and anti-KSHV activity is with the chemical combination shown in following formula (I)
Thing 1 is to compound 18：
Compound 1：Hypericum japonicum dextrorotation anti EB virus element A [(+)-hyperjaponol A (1)]
Compound 2：The left-handed anti EB virus element A of hypericum japonicum [(-)-hyperjaponol A (2)]
Compound 3：Hypericum japonicum dextrorotation anti EB virus element B [(+)-hyperjaponol B (3)]
Compound 4：The left-handed anti EB virus element B of hypericum japonicum [(-)-hyperjaponol B (4)]
Compound 5：Hypericum japonicum dextrorotation anti EB virus element C [(+)-hyperjaponol C (5)]
Compound 6：The left-handed anti EB virus element C of hypericum japonicum [(-)-hyperjaponol C (6)]
Compound 7：Hypericum japonicum anti EB virus element D (hyperjaponol D), R=CH (CH3)2
Compound 8：Hypericum japonicum anti EB virus element E (hyperjaponol E),
Compound 9：Hypericum japonicum anti EB virus element F (hyperjaponol F),
Compound 10：Hypericum japonicum pannol G (hyperjaponol G)
Compound 11：The anti-KS blister sores toxin A of hypericum japonicum dextrorotation [(+)-japonicol A (11)]
Compound 12：The left-handed anti-KS blister sores toxin A [(-)-japonicol A (12)] of hypericum japonicum
Compound 13：The anti-KS blister sores toxin B of hypericum japonicum dextrorotation [(+)-japonicol B (13)]
Compound 14：The left-handed anti-KS blister sores toxin B [(-)-japonicol B (14)] of hypericum japonicum
Compound 15：The anti-KS blister sores toxin C of hypericum japonicum dextrorotation [(+)-japonicol C (15)]
Compound 16：The left-handed anti-KS blister sores toxin C [(-)-japonicol C (16)] of hypericum japonicum
Compound 17：The anti-KS blister sores toxin D of hypericum japonicum dextrorotation [(+)-japonicol D (17)]
Compound 18：The left-handed anti-KS blister sores toxin D [(-)-japonicol D (18)] of hypericum japonicum
Formula (I)
We are under the guidance of antiviral activity screening, to picking up from Hubei Province Qichun County Dabie Mountains Region and picking up from Jiangxi Province
The hypericum japonicum of Mount Lushan city In The Lushan Area has carried out the antiviral activity composition Study of system, isolated 18 noval chemical compounds.
Wherein, the isolated compound 1-10 from the hypericum japonicum for picking up from Hubei Province Qichun County Dabie Mountains Region, from picking up from Jiangxi Province's hut
The isolated compound 11-18 of nostoc commune grass seeds of Shan Shi In The Lushan Areas.Shown in structural formula such as formula (I).
Antiviral activity researchs are carried out to two kinds of tumorigenesis herpesvirals by this 18 compounds, find compound 1,3,4,
The DNA replication dna of 7 and 8 pairs of Epstein-Barr virus has inhibitory activity；Compound 3,6 and 13-17 are to Kaposi's sarcoma associated herpesvirus
(KSHV) burst times is replicated with inhibitory activity.Prepared the present invention relates to the separation of compound in hypericum japonicum and it has suppression
Make the activity of virus.Compound 1,3,4,7 and 8 is it is expected that develop into treatment lupus erythematosus as caused by Epstein-Barr virus, rheumatism
Property arthritis and nasopharyngeal carcinoma, Hodgkin's disease, T/B lymphocytomas, Burkitt ' S lymthomas and the B of immune deficiency patient
The medicine of the tumor diseases such as lymphocytoma；Compound 3,6 and 13-17 are expected to develop into treatment card as caused by KSHV
The medicine of the diseases such as Podbielniak sarcoma, lymphoma primary effusion and multicenter Calve disease.It this completes the present invention.
The present inventor is carried out by the ethanol extract of the hypericum japonicum herb to picking up from Hubei Province Qichun County Dabie Mountains Region
Isolate and purify, obtain 10 noval chemical compounds, i.e. compound 1-10.Hypericum japonicum herb to picking up from Lushan, Jiangxi city In The Lushan Area
Ethanol extract isolated and purified, obtain 8 noval chemical compounds, i.e. compound 11-18.With a variety of analysis method by use of spectrum and
Other means, it is miscellaneous terpenoid to determine their structure, shown in concrete structure such as formula (I).By to compound 1-18's
Antiviral activity is evaluated, it is found that compound 1,3,4 and 7-9 are induced Epstein-Barr virus in B95-8 cells with phorbol exters (PMA/TPA)
After carry out cracking duplication, show the activity of good suppression viral dna replication, the activity of wherein compound 3 and 7 is especially aobvious
Write, can be as the potential drug for suppressing Epstein-Barr virus drug development；It was found that compound 3,6 and 13-17 to KSHV in iSLK.219
With cracking duplication is carried out after tetracycline (Dox) and sodium butyrate (NaB) induction in cell, it is multiple to show good suppression KSHV cracking
The activity of system, the wherein activity of compound 13 is more notable, can be as the lead compound for suppressing KSHV drug developments.
Another task of the present invention is to provide applications of the compound 1-18 in antiviral drugs is prepared shown in formula (I).
When for compound 3 and 7 when, described antiviral drugs is preferably the medicine of anti EB virus.When for compound 13 when, it is described anti-
Virus drugs are preferably anti-KSHV.
Brief description of the drawings
Fig. 1：Compound hypericum japonicum dextrorotation antivirotic B shown in formula (1), the left-handed antivirotic B of hypericum japonicum, hypericum japonicum are disease-resistant
Toxin D and the plain C of the left-handed anti-KS viruses of hypericum japonicum Structural Identification.It is left-handed to compound hypericum japonicum dextrorotation antivirotic B, hypericum japonicum
Antivirotic B, hypericum japonicum antivirotic D and the plain C of the left-handed anti-KS viruses of hypericum japonicum carry out mass spectrum, ultraviolet spectra, infrared spectrum, rotation
Light, nuclear magnetic resonance, the data test such as circular dichroism spectra and X ray single crystal diffraction, so that it is determined that the structure of compound.The He of compound 3
4：UV(CH3OH)λmax(log ε)=227 (3.22), 242 (3.25), 325 (3.28) nm；IRνmax=3460,2963,2930,
1658,1624,1553,1474,1383cm–1；for1H NMR(600MHz)and 13C NMR(150MHz)data see
Table 1and 2；HRESIMS[M+H]+m/z 457.2946(calcd for C28H41O5,457.2954)。3:Colorless
oil,+135.4(c 0.03,MeOH)；ECD(MeOH)λ(Δε)216(+13.01)nm；4:Colorless
amorphous powder,-134.5(c 0.03,MeOH)；ECD(MeOH)λ(Δε)217(-10.91)nm.Compound
The determination of 3 and 4 absolute configuration is the method by calculating ECD.The surveyed CD (circular dichroism spectra) of experiment Cotton effects with
Calculated value coincide.As shown in Figure 1.
Fig. 2：Compound 7：orange-red oil,+64.7(c 0.11,MeOH)；ECD(MeOH)λ(Δε)227
(+3.23),272(+0.78),317(+0.74)nm；UV(CH3OH)λmax(log ε)=229 (3.64), 240 (3.15), 329
(3.26)nm；IRνmax=3521,3054,2980,2933,2873,1659,1626,1475,1383cm–1；for1H NMR
(400MHz)and 13C NMR(100MHz)data see Table 1and 2；HRESIMS[M+H]+m/z 475.3046
(calcd for C28H43O6,475.3060).The determination of the absolute configuration of compound 7 is the method by calculating ECD.Experiment is surveyed
CD (circular dichroism spectra) Cotton effects coincide with calculated value.As shown in Figure 2.
Fig. 3：The crystal structure of compound 16 is as shown in Figure 3.
Embodiment
Embodiment 1：Compound hypericum japonicum dextrorotation antivirotic B, the left-handed antivirotic B of hypericum japonicum, hypericum japonicum antivirotic D
Preparation and Structural Identification with the plain C of the left-handed anti-KS viruses of hypericum japonicum.
(1) compound hypericum japonicum dextrorotation antivirotic B, the left-handed antivirotic B of hypericum japonicum, hypericum japonicum resist as shown in formula (1)
The plain D of virus and the plain C of the left-handed anti-KS viruses of hypericum japonicum preparation
1. the collection of hypericum japonicum (Hypericum japocicum)：
Pick up from the hypericum japonicum of Hubei Province Qichun County Dabie Mountains Region：October gathers herb 50kg, dries, and is dried in vacuo
Afterwards, it is stored in Pharmaceutical College, Tongji Medical College, Central-China Science ＆. Technol's Chinese herbal medicine sample storehouse.
Pick up from the hypericum japonicum of Lushan, Jiangxi city In The Lushan Area：August part gathers herb, dries, after vacuum drying, is stored in
Pharmaceutical College, Tongji Medical College, Central-China Science ＆. Technol's Chinese herbal medicine sample storehouse.
2. extraction：
Solvent extraction method is used, after dry hypericum japonicum herb is crushed, 95% ethanol is added and carries out seepage pressure effects 4
It is secondary.Be concentrated under reduced pressure recovery ethanol at less than 40 DEG C.The hypericum japonicum of Hubei Province Qichun County Dabie Mountains Region is picked up from, obtains 230.0g leachings
Cream；The hypericum japonicum of Lushan, Jiangxi city In The Lushan Area is picked up from, obtains 130.0g medicinal extract.
3. separation：
230.0g total medicinal extract (hypericum japonicum for picking up from Hubei Province Qichun County Dabie Mountains Region) is mixed with 100-200 mesh silica gel
Sample, after dry column-packing, with petroleum ether-acetone gradient elution (100:1–5:1), TLC is detected, and is merged identical component, is obtained 5
Individual component.For component 3 again by positive reversed-phase silica gel column chromatography repeatedly, gel chromatography and high performance liquid chromatography separation obtain compound
Hypericum japonicum antivirotic B (3.7mg), and chiral resolution is carried out by chiral preparatory column, it is different to obtain the equal mapping of a pair of mass
Structure body, i.e. (±)-hyperjaponol B (3 and 4)；Component 4 is by positive reversed-phase silica gel column chromatography repeatedly, gel chromatography and height
Effect liquid phase chromatogram assigns to compound hypericum japonicum antivirotic D (10.1mg), i.e. hyperjaponol D；
By 130.0g total medicinal extract (hypericum japonicum for picking up from Lushan, Jiangxi city In The Lushan Area) with 120 mesh silica gel mixed samples, do
After method dress post, with petroleum ether-ethyl acetate gradient elution (100:1–5:1), TLC is detected, and after merging same composition, obtains 8
Component.For component 7 by positive reversed-phase silica gel column chromatography repeatedly, gel chromatography and high performance liquid chromatography separation assign to compound nostoc commune
The grass plain C of anti-KS viruses, i.e. (±)-japonicol C (5.1mg), then carry out chiral resolution with chiral preparatory column, obtain a pair
The equal enantiomter of quality, i.e. (±)-japonicol C (15 and 16).
(2) compound hypericum japonicum dextrorotation antivirotic B, the left-handed antivirotic B of hypericum japonicum, hypericum japonicum resist as shown in formula (1)
The plain D of virus and the plain C of the left-handed anti-KS viruses of hypericum japonicum Structural Identification
To compound hypericum japonicum dextrorotation antivirotic B, the left-handed antivirotic B of hypericum japonicum, hypericum japonicum antivirotic D and nostoc commune
The plain C of the left-handed anti-KS viruses of grass carries out mass spectrum, ultraviolet spectra, infrared spectrum, optically-active, nuclear magnetic resonance, circular dichroism spectra and X ray monocrystalline
The data tests such as diffraction, so that it is determined that the structure of compound.
Compound 3 and 4：UV(CH3OH)λmax(log ε)=227 (3.22), 242 (3.25), 325 (3.28) nm；IRνmax
=3460,2963,2930,1658,1624,1553,1474,1383cm–1；for1H NMR(600MHz)and 13C NMR
(150MHz)data see Table 1and 2；HRESIMS[M+H]+m/z 457.2946(calcd for C28H41O5,
457.2954)。3:Colorless oil,+135.4(c 0.03,MeOH)；ECD(MeOH)λ(Δε)216(+13.01)
nm；4:Colorless amorphous powder,-134.5(c0.03,MeOH)；ECD(MeOH)λ(Δε)217(-
10.91)nm.The determination of the absolute configuration of compound 3 and 4 is the method by calculating ECD.The surveyed CD (circular dichroism spectra) of experiment
Cotton effects coincide with calculated value.As shown in Figure 1.
Compound 7：orange-red oil,+64.7(c 0.11,MeOH)；ECD(MeOH)λ(Δε)227(+
3.23),272(+0.78),317(+0.74)nm；UV(CH3OH)λmax(log ε)=229 (3.64), 240 (3.15), 329
(3.26)nm；IRνmax=3521,3054,2980,2933,2873,1659,1626,1475,1383cm–1；for1H NMR
(400MHz)and 13C NMR(100MHz)data see Table 1and 2；HRESIMS[M+H]+m/z 475.3046
(calcd for C28H43O6,475.3060).The determination of the absolute configuration of compound 7 is the method by calculating ECD.Experiment is surveyed
CD (circular dichroism spectra) Cotton effects coincide with calculated value.As shown in Figure 2.
Compound 16：Colorless crystal,-100.6(c 0.24,MeOH)；UV(CH3OH)λmax(logε)
=203 (4.49), 226 (4.37), 289 (4.31) nm；IRνmax=3225,2964,2927,2854,1718,1619,1494,
1460,1420cm–1；ECD(MeOH)λ(Δε)218(+6.80),275(+2.78),307(-10.72)nm；for1H NMR
(400MHz)and 13C NMR(100MHz)datasee Table 1and 2；HRESIMS[M+Na]+m/z 371.1807
(calcd for C20H28O5Na,371.1834).The determination of the absolute configuration of compound 16 is the side by X ray single crystal diffraction
Method.16 crystal structures are as shown in Figure 3.
Embodiment 2：Inhibitory activity of the compound 1-10 to the DNA replication dna of Epstein-Barr virus；Compound 1-18 cracks multiple to KSHV
The inhibitory activity of system.
The evaluation of compound 1-10 anti EB virus activity：Employ firstcell viability
Toxic action of reagent kits (thermofisher) the detection compound thing to cell；Then using with EBV viruses
B95-8 cells crack reconstructed model as compound is assessed to EBV, and it is multiple to enter cracking using TPA (20ng/mL) activation EBV
System, EBV gene copy numbers are detected by QPCR method and assess influence of the compound to duplication.
The evaluation of compound 1-18 anti-KSHV activity：Employ firstcell viability
Toxic action of reagent kits (thermofisher) detection compound to cell；Then restructuring GFP be present using latent
The cell line iSLK.219 of the KSHV viruses of gene cracks reconstructed model as compound is assessed to EBV, is combined using Dox
NaB induces KSHV to be replicated into burst times, the fluorescence intensity that GFP is expressed in observation and analysis Vero cells, so as to learn compound
Horizontal influence is produced to infectious viral particle in cell supernatant.As a result as shown in Table 3.
Table 1.1H NMR data for compounds 3/4,7,and 16(400MHz,J in Hz,in
CDCl3)
a600MHz
Table 2.13C NMR for compounds 3/4,7,and 16(100MHz,J in Hz)
a150MHz
Table 3.anti-EBV activities of compounds 1–10.
Table 4.anti-KSHV activities of compounds 1–18.
Note：It is CC to select index (SI)50/EC50The value of gained, for judging the effect of medicine, SI can be considered have more than 3
Effect, index is bigger, and explanation Antiviral Effect effect is better, in general if the SI values of medicine are more than 10, and EC50Value is relatively
Low (being less than 100 μM), then the medicine can be developed as potential drug.
Experiment conclusion：Compound 1,3,4,7 and 8 shows relatively low toxicity and higher selection index, can be used as suppression
The lead compound of Epstein-Barr virus drug development processed, also, wherein especially notable, the EC of activity of compound 3 and 750Far below sun
Property medicine Gancilovir, and the selection index of compound 7 is higher than Gancilovir, can be used as potential anti EB virus medicine
Developed；Compound 13-17 shows hypotoxicity and higher selection index, can be as the elder generation for suppressing KSHV drug developments
Lead compound.
Claims (9)
1. there is the compound shown in any structure in following structural formula 3,4,7,15 and 16,
Compound 3：Hypericum japonicum dextrorotation anti EB virus element B
Compound 4：The left-handed anti EB virus element B of hypericum japonicum
Compound 7：Hypericum japonicum anti EB virus element D, R=CH (CH3)2
Compound 15：The anti-KS blister sores toxin C of hypericum japonicum dextrorotation
Compound 16：The left-handed anti-KS blister sores toxin C of hypericum japonicum.
2. the preparation method of the compound 3 and compound 4 described in claim 1, comprises the following steps：Using solvent extraction
Method, after dry hypericum japonicum herb is crushed, add 95% ethanol and carry out seepage pressure effects 4 times, less than 40 DEG C at be concentrated under reduced pressure back
Receive ethanol and obtain medicinal extract；By total medicinal extract of gained 100-200 mesh silica gel mixed samples, after dry column-packing, with petroleum ether-acetone gradient
Elution, gradient 100:1–5:1, TLC detection, merges identical component, 5 components is obtained, component 3 is again by repeatedly
Positive reversed-phase silica gel column chromatography, gel chromatography and high performance liquid chromatography separation obtain compound hypericum japonicum antivirotic B, and pass through
Chiral preparatory column carries out chiral resolution, obtains the equal enantiomter of a pair of mass, i.e. compound 3 and compound 4.
3. the preparation method of the compound 7 described in claim 1, comprises the following steps：, will be dry using solvent extraction method
After hypericum japonicum herb crushes, add 95% ethanol and carry out seepage pressure effects 4 times, less than 40 DEG C at the recovery ethanol that is concentrated under reduced pressure soaked
Cream；The total medicinal extract 100-200 mesh silica gel mixed samples that will be obtained, after dry column-packing, with petroleum ether-acetone gradient elution, elution ladder
Spend for 100:1–5:1, TLC detection, merges identical component, 5 components is obtained, component 4 is by positive reverse phase silica gel repeatedly
Column chromatography, gel chromatography and high performance liquid chromatography separation assign to compound hypericum japonicum antivirotic D, i.e. compound 7.
4. the preparation method of the compound 15 and compound 16 described in claim 1, comprises the following steps：Using solvent extraction
Method, after dry hypericum japonicum herb is crushed, add 95% ethanol and carry out seepage pressure effects 4 times, less than 40 DEG C at be concentrated under reduced pressure back
Receive ethanol and obtain medicinal extract；By obtained total medicinal extract with 120 mesh silica gel mixed samples, after dry column-packing, with petroleum ether-ethyl acetate gradient
Elution, gradient 100:1–5:1, TLC detection, after merging same composition, 8 components are obtained, component 7 is passed through repeatedly just
Reversed-phase silica gel column chromatography, gel chromatography and high performance liquid chromatography separation assign to the compound hypericum japonicum plain C of anti-KS viruses, then use hand
Property prepare post carry out chiral resolution, obtain the equal enantiomter of a pair of mass, as compound 15 and compound 16.
5. application of the compound in preparing for antiviral drugs described in claim 1.
6. 3,4 or 7 application in anti EB virus medicine is prepared of compound described in claim 1.
7. the answering in anti-Kaposi's sarcoma associated herpesvirus medicine is prepared of the compound 3,15 or 16 described in claim 1
With.
8. a kind of antiviral drugs preparation, it is characterised in that compound and pharmaceutically acceptable added as described in claim 1
Add antiviral agent made of agent.
9. pharmaceutical preparation according to claim 8, it is characterised in that described medicament is injection, powder-injection, oral
Agent, spray, capsule or suppository.
Priority Applications (1)
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| Anti-Tumor-Promoting Activities of Euglobals from Eucalyptus Plants;Midori Takasaki等;《Biol. Pharm. Bull.》;19951231;第18卷(第3期);参见第436页表1化合物5和16 * |
| 天然产物中三萜类化合物的抗病毒研究;孟正等;《中华中医药学刊》;20110531;第28卷(第5期);全文 * |
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