CN108358948B - Tetraterpenes compound and its preparation method and application - Google Patents
Tetraterpenes compound and its preparation method and application Download PDFInfo
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Abstract
A kind of method that preparation is extracted the present invention provides tetraterpenes compound and its from disk meat sesame soft coral, the tetraterpenes compound for inventing offer has T cell hypotype regulation activity, and cytotoxicity is low, can be used for preparing immunoregulation medicament.The tetraterpenes compound also is used as lead compound, and the drug to develop new opens new approach.
Description
Technical field
The present invention relates to pharmaceutical technology fields, more particularly to a kind of tetraterpenes compound and its preparation method and application.
Background technique
Disk meat sesame soft coral (latin name Sarcophyton trocheliophorum) belongs to Alcyonaria
(Octocorallia), soft coral mesh (Alcyonacea), Alcyoniidae (Alcyoniidae) animal.1974 from
Isolated sarcophine indicates the beginning that terpenoid is studied in meat sesame soft coral category coral in S.glaucum
【Ne′eman I,Fishelson L,Kashman Y.Sarcophine.New toxin from the soft coral
Sarcophyton glaucum(Alcyonaria).Toxicon,1974,12(6):593-598.].Nearly 40 years hereafter
In time, terpenoid in coral gradually becomes natural products because of its Chemical Diversity abundant and significant bioactivity
One of hot spot of research.
Also containing one kind, structure is complicated, the unique tetraterpene compound of skeleton in coral, and the structure feature of such compound is
Two Cesong alkyl type diterpines are combined together by a cyclohexene unit, and the substituent group on dimerization Cystatins C molecule passes through
Different degrees of oxidation causes the multiple types such as hydroxyl, ether, carboxymethyl and lactone functional group, and biosynthesis viewpoint thinks
It is to be synthetically formed by two Cystatins Cs by intermolecular Diels-Alder reac-tions.Guo Yuewei seminar is in recent years
Dimerization Cystatins C compound in the meat soft coral of report be reviewed [Li Yufen, Liang Linfu, Xiao Wei, Liang Jingyu,
The chemical and biological activity progress organic chemistry of dimerization Cesong alkyl type diterpine compound in Guo Yuewei meat sesame soft coral category
2013,33:1157-1166.】
Early period, researcher once carried out much disk meat sesame soft coral Sarcophyton trocheliophorum
Research, therefrom has found polyhydroxy sterol [(1) Dong, H.；Gou,Y.L.；Kini,R.M.；Xu,H.X.；Chen,S.X.；
Teo,S.L.；But,P.P.A new cytotoxic polyhydroxysterol from soft coral
Sarcophyton trocheliophorum.Chem.Pharm.Bull.2000,48,1087-1089；(2)Chen,W.T.；
Liu,H.L.；Yao,L.G.；Guo,Y.W.9,11-Secosteroids and polyhydroxylated steroids
from two South China Sea soft corals Sarcophyton trocheliophorum and
Sinularia flexibilis.Steroids 2014,92,56-61.], sequiterpene [Anjaneyulu, A.S.；Rao,
V.L.；Sastry,V.G.；Rao,D.V.Trocheliophorin:a novel rearranged sesquiterpenoid
from the Indian Ocean soft coral Sarcophyton trocheliophorum.J.Asian Nat Prod
Res 2008,10,597-601.], Cesong alkyl type diterpine [(1) Grote, D.；Soliman,H.S.；Shaker,K.H.；
Hamza,M.；Seifert,K.Cembranoid diterpenes and a briarane diterpene from
corals.Nat.Prod.Res.2006,20,285-291；(2)Liang,L.F.；Gao,L.X.；Li,J.；
Taglialatela-Scafati,O.；Guo,Y.W.Cembrane diterpenoids from the soft coral
Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors.B
ioorg.Med.Chem.Lett.2013,21,5076-5080；(3)Liang,L.-F.；Lan,L.-F.；Taglialatela-
Scafati,O.；Guo,Y.-W.Sartrolides A-G and bissartrolide,new cembranolides from
the South China Sea soft coral Sarcophyton trocheliophorum
Marenzeller.Tetrahedron 2013,69,7381-7386；(4)Liang,L.F.；Chen,W.T.；Mollo,E.；
Yao,L.G.；Wang,H.Y.；Xiao,W.；Guo,Y.W.Sarcophytrols G-L,Novel Minor Metabolic
Components from South China Sea Soft Coral Sarcophyton trocheliophorum
Marenzeller.Chem.Biodivers.2017,14,Epub,doi:10.1002/cbdv.201700079；(5)Liang,
L.F.；Chen,W.T.；Li,X.W.；Wang,H.Y.；Guo,Y.W.New Bicyclic Cembranoids from the
South China Sea Soft Coral Sarcophyton trocheliophorum.Sci.Rep.2017,7,46584；
(6)Liu,K.M.；Cheng,C.H.；Chen,W.F.；Lu,M.C.；Fang,L.S.；Wen,Z.H.；Su,J.H.；Wu,Y.C.；
Sung,P.J.Trocheliolide A,a Hydroperoxycembranoidal Diterpene from the
Octocoral Sarcophyton trocheliophorum.Nat.Prod.Commun.2015,10,1163-1165；(7)
Liu,K.M.；Lan,Y.H.；Su,C.C.；Sung,P.J.Trocheliolide B,a New Cembranoidal
Diterpene from the Octocoral Sarcophyton trocheliophorum.Nat.Prod.Commun.20
16,11,21-22；(8)Chen,W.T.；Liang,L.F.；Li,X.W.；Xiao,W.；Guo,Y.W.Further New
Highly Oxidative Cembranoids from the Hainan Soft Coral Sarcophyton trocheli
] and Furanones ingredient [Gomaa, M.N. ophorum.Nat.Prod.Bioprospect.2016,6,97-102.；
Soliman,K.；Ayesh,A.；Abd El-Wahed,A.；Hamza,Z.；Mansour,H.M.；Khalifa,S.A.；Mohd
Ali,H.B.；El-Seedi,H.R.Antibacterial effect of the red sea soft coral
Sarcophyton trocheliophorum.Nat.Prod.Res.2015,1-6.].But before this patent, there has been no from circle
The report of dimerization Cesong alkyl type diterpine is found in disk meat soft coral.
Summary of the invention
Based on this, the object of the present invention is to provide a kind of tetraterpenes compound of dimerization Cesong alkyl type diterpine, the tetraterpenes
Compound has the expression of one of following structural formula:
The tetraterpenes compound extracts from disk meat sesame soft coral in one of the embodiments,.
A kind of application of the tetraterpenes compound in immunoregulation medicament, anti-tumor drug or antibacterials.
A kind of preparation method of the tetraterpenes compound, comprising:
S1 is provided and is crushed disk meat sesame soft coral；
S2 obtains the disk meat sesame soft coral methanol and/or acetone extraction of the crushing after the concentration of gained extracting solution
First medicinal extract；
First medicinal extract is suspended in water, and is extracted with ether by S3, obtains ether extraction liquid, the ether extraction
The second medicinal extract is obtained after liquid concentration；
Second medicinal extract is suspended in methanol aqueous solution by S4, and with n-hexane extraction, will be by the n-hexane extraction
Third medicinal extract is obtained after methanol aqueous solution concentration afterwards；
The third medicinal extract is carried out silica gel column chromatography separation by S5, is flowing with the mixed solution of methylene chloride and methanol
Gradient elution is mutually carried out, successively obtains fraction 1 to fraction 14；And
Fraction 7 of the fraction 1 into fraction 14 is carried out glucose gel chromatography, with the mixing of methanol and chloroform by S6
Solution is that mobile phase is eluted, and successively obtains fraction 71 to fraction 77, fraction 73 of the fraction 71 into fraction 77 is used
High performance liquid chromatography is isolated and purified, and obtains compound bistrochelide E, compound bistrochelide C respectively
With compound bistrochelide D；And/or
Fraction 8 of the fraction 1 into fraction 14 is subjected to glucose gel chromatography, with the mixed solution of methanol and chloroform
It is eluted for mobile phase, successively obtains fraction 81 to fraction 85, by fraction 84 of the fraction 81 into fraction 85 with efficiently
Liquid chromatogram is purified, and obtains compound glaucumolide A, compound glaucumolide B, compound respectively
Bistrochelide B and compound bistrochelide A.
In one of the embodiments, in the step S5, using the mixed solution of methylene chloride and methanol as mobile phase
Carry out gradient elution the step of include:
In the mixed liquor for making the methylene chloride and methanol, the volume ratio of the methylene chloride and the methanol is from 100:1
Gradient elution is carried out to 1:1.
The volume ratio of methanol and chloroform is 1:1.2 in the mixed liquor of the methanol and chloroform in one of the embodiments,
To 1.2:1.
The glucose gel of the fraction 7 and/or the fraction 8 chromatography can be used in one of the embodiments,
Sephadex LH-20 gel column carries out.
The content of methanol is 80wt% to 95wt% in the methanol aqueous solution in one of the embodiments,.
In one of the embodiments, in the step S2 by the disk meat sesame soft coral methanol of the crushing and/or
The step of acetone extraction includes:
The disk meat sesame soft coral of the crushing is multiple with acetone ultrasonic extraction, obtain acetone extract, again with methanol
Ultrasonic extraction is multiple, obtains methanol extract liquid, merges the acetone extract and the methanol extract liquid, obtains the extraction
Liquid.
The fraction 73 or the fraction 84 are isolated and purified with high performance liquid chromatography in one of the embodiments,
When, mobile phase used be 70%~80% acetonitrile solution.
Present invention separation and Extraction from disk meat soft coral obtains the loose alkane type in the west of the dimerization in seven kinds of tetraterpenes compounds
Diterpene compound.Tetraterpenes compound provided by the invention has T cell hypotype regulation activity, and cytotoxicity is low, can use
In preparing immunoregulation medicament.The tetraterpenes compound also is used as lead compound, and the drug to develop new opens newly
Approach.
Detailed description of the invention
Fig. 1 is effect of vigor test data figure of the tetraterpenes compound provided by the invention to mouse boosting cell；
Fig. 2 is proliferative effect test data figure of the tetraterpenes compound provided by the invention to mouse CD3+T sub-types of cells；
Fig. 3 is influence of the tetraterpenes compound provided by the invention to mouse CD4+T sub-types of cells and CD8+ sub-types of cells
Test data figure.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, by the following examples, it and combines attached
Figure, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only to explain this hair
It is bright, it is not intended to limit the present invention.
The present invention is extracted from disk meat sesame soft coral and isolated seven kinds of tetraterpenes compound glaucumolide A
It is respectively as follows: with the chemical structural formula of glaucumolideB and bistrochelide A-E, seven kinds of tetraterpenes compounds
Compound glaucumolide A, the glaucumolide B and bistrochelide A-E belongs to dimerization
Cesong alkyl type diterpine.Compound glaucumolide A, the glaucumolide B and bistrochelide A-E has good
Good antitumor and antibacterial activity, can be applied in immunoregulation medicament.The compound glaucumolide A,
Glaucumolide B and bistrochelide A-E can also be used as lead drug for researching and developing new drug.
The present invention also provides the compound glaucumolide A is extracted and separated from disk meat sesame soft coral,
The method of glaucumolide B and bistrochelide A-E, specifically can include:
S1 is provided and is crushed disk meat sesame soft coral；
S2 obtains the disk meat sesame soft coral methanol and/or acetone extraction of the crushing after the concentration of gained extracting solution
First medicinal extract；
First medicinal extract is suspended in water, and is extracted with ether by S3, obtains ether extraction liquid, the ether extraction
The second medicinal extract is obtained after liquid concentration；
Second medicinal extract is suspended in methanol aqueous solution by S4, and with n-hexane extraction, will be by the n-hexane extraction
Third medicinal extract is obtained after methanol aqueous solution concentration afterwards；
The third medicinal extract is carried out silica gel column chromatography separation by S5, is flowing with the mixed solution of methylene chloride and methanol
Gradient elution is mutually carried out, successively obtains fraction 1 to fraction 14；And
Fraction 7 of the fraction 1 into fraction 14 is carried out glucose gel chromatography, with the mixing of methanol and chloroform by S6
Solution is that mobile phase is eluted, and successively obtains fraction 71 to fraction 77, fraction 73 of the fraction 71 into fraction 77 is used
High performance liquid chromatography is isolated and purified, and obtains compound bistrochelide E, compound bistrochelide C respectively
With compound bistrochelide D；And/or
Fraction 8 of the fraction 1 into fraction 14 is subjected to glucose gel chromatography, with the mixed solution of methanol and chloroform
It is eluted for mobile phase, successively obtains fraction 81 to fraction 85, by fraction 84 of the fraction 81 into fraction 85 with efficiently
Liquid chromatogram is purified, and obtains compound glaucumolide A, compound glaucumolide B, compound respectively
Bistrochelide B and compound bistrochelide A.
In step sl, the disk meat sesame soft coral can be acquired from the Chinese Xisha Islands.
In step s 2, the disk meat sesame soft coral methanol and/or acetone of the crushing are slightly mentioned.It can will be described
The disk meat sesame soft coral methanol and/or acetone of crushing carry out ultrasonic wave extraction.It can be used methanol and/or acetone to the powder
Broken disk meat sesame soft coral is repeatedly extracted.It in one embodiment, can be by the disk meat sesame soft coral of the crushing with third
Ketone ultrasonic extraction is multiple, obtains acetone extract, and again with methanol ultrasonic extraction is multiple, obtains methanol extract liquid, merges described third
Ketone extracting solution and the methanol extract liquid, obtain the extracting solution.
In step s 4, the content of methanol can be 80wt% to 95% in the methanol aqueous solution, may be, for example, 90wt%.
In step s 5, the step of carrying out gradient elution as mobile phase using the mixed solution of methylene chloride and methanol can be with
It is to make in the mixed solution of the methylene chloride and methanol, the volume ratio of methylene chloride and methanol carries out gradient change from big to small
Change, such as change of gradient can be carried out from 100:1 to 1:1.
In step s 6, the volume ratio of methanol and chloroform can be for 1:1.2 extremely in the mixed solution of the methanol and chloroform
1.2:1 may be, for example, 1:1.Sephadex LH-20 can be used in the glucose gel of the fraction 7 and/or the fraction 8 chromatography
Gel column carries out.When the fraction 73 or the fraction 84 are isolated and purified with high performance liquid chromatography, mobile phase used is
70%~80% acetonitrile-aqueous solution.
It is prepared by the separation of embodiment 1glaucumolide A, glaucumolide B, bistrochelide A-E
Select the disk meat sesame soft coral Sarcophyton trocheliophorum sample of Chinese Xisha Islands acquisition
(weight in wet base 3.2kg) is shredded, then is crushed with machine, and acetone ultrasonic extraction 5 times, again with methanol ultrasonic extraction 3 times, every time
1.5L, 30 minutes, until extracting solution is substantially colorless.Merge acetone and methanol extract liquid, coarse extract is concentrated under reduced pressure to obtain, coarse extract is used
The distilled water ultrasound of 1L is suspended, and extracts 5 times (1L/ times) with ether, merges ether extraction liquid, is concentrated under reduced pressure, obtains brown ether layer
Medicinal extract 61g.Ether layer medicinal extract is suspended with the 90% methanol-water solution ultrasound of 0.5L, with n-hexane extraction 5 times (0.5L/ times), is closed
And n-hexane layer extract liquor, brown medicinal extract 100g is concentrated under reduced pressure to obtain, bronzing is concentrated under reduced pressure to obtain in 90% methanol-water solution of residue
Medicinal extract 12g.
By 12g bronzing medicinal extract, sample is mixed in 20g silica gel (300-400 mesh), through 300g normal-phase silica gel column chromatography (column internal diameter
About 5cm, pillar height about 25cm, 200-300 mesh silica gel), with methylene chloride/methanol gradient elution (100:1-1:1), according to
The monitoring of HSGF254 lamellae, and developed the color by 10% sulfuric acid vanillic aldehyde, it is collected respectively by fraction polarity size, collects merge altogether
14 fraction, that is, fractions 1 are obtained to fraction 14 (Fr.1~Fr.14).Fr.7 is passed through into Sephandex LH-20 gel column chromatography layer
It analyses (column internal diameter about 2cm, pillar height about 143cm), mobile phase is methanol: chloroform=1:1 is collected by automatic receptor, lamellae prison
Survey, be divided into 7 flow point Fr.71~77, wherein Fr.73 isolated and purified with semi-preparative HPLC (70% acetonitrile-aqueous solution,
Flow velocity: 2mL/min), it obtains compound 7 (4.2mg, tR=34.5min), compound 5 (59.6mg, tR=49.5min) and change
It closes object 6 (8.8mg, tR=52.8min).Fr.8 is chromatographed by Sephandex LH-20 gel column chromatography, and mobile phase is methanol:
Chloroform=1:1, is collected by automatic receptor, and lamellae monitoring is divided into 5 flow point Fr.81~85, and wherein Fr.84 is prepared with half
Type HPLC is isolated and purified (74% acetonitrile-aqueous solution, flow velocity: 2mL/min), and compound 1 (112.8mg, tR=are obtained
32.1min), compound 2 (194.5mg, tR=38.1min), compound 4 (62.1mg, tR=43.5min) and compound 3
(4.4mg, tR=45.4min).
The Structural Identification of 2 compound of embodiment
The present invention divides from Chinese Xisha Islands of South China Sea disk meat sesame soft coral Sarcophyton trocheliophorum
From obtained compound 1-7, correspondence is named as glaucumolide A, glaucumolide B, bistrochelide A-E,
And to compound glaucumolide A, glaucumolide B, the bistrochelide A-E (i.e. compound 1-7) into
The test of row nuclear magnetic resonance, specific data are as follows:
Glaucumolide A (compound 1): white crystal；Optical activity(c 1.1,MeOH)；Electronics
Circular dichroism spectra ECD (MeOH, c 4.3 × 10-4)λmax(Δ ε)=205 (+46.9), 235 (- 14.3) nm；Solid circular dichroism spectra ECD
(KCl)λmax(Φ)=205 (+27.7), 236 (- 13.9), 375 (+1.4) nm；UV absorption data UV (MeOH) λmax(logε)
203(4.04),242(3.83)nm；Infrared absorption data IR (film) νmax=3469,2944,1676,1737,1681,1606,
1453 1238cm-1.1H and13C NMR data is shown in Table 1-3；High resolution mass spectrum HRESIMS [M+NH4]+m/z:708.4476
(calcd for C42H62NO8,708.4475)。
Glaucumolide B (compound 2): white amorphous powder；Optical activity(c 0.7,
MeOH)；Electronic circular dichroism ECD (MeOH, c 4.3 × 10-4)λmax(Δ ε)=203 (+27.3), 233 (- 4.6), 255 (-
6.6)nm；UV absorption data UV (MeOH) λmax(logε)203(4.07),242(3.88)nm；Infrared absorption data IR
(film)νmax=3464,2946,1765,1737,1682,1607,1439,1239cm-1.1H and13C NMR data is shown in Table 1-3；
High resolution mass spectrum HRESIMS [M+H]+m/z:691.4209(calcd for C42H59O8,691.4204)。
Bistrochelide A (compound 3): white amorphous powder；Optical activity(c 0.8,
MeOH)；Electronic circular dichroism ECD (MeCN, c 4.0 × 10-4)λmax(Δ ε)=205 (+9.11), 253 (- 2.84) nm；It is ultraviolet
Absorb data UV (MeOH) λmax(logε)201(3.77),244(3.43)nm；Infrared absorption data IR (film) νmax=3465,
2935,1959,1737,1682,1606,1444,1239cm-1.1H and13C NMR data is shown in Table 1-3；High resolution mass spectrum HRESIMS
[M+NH4]+m/z:708.4468(calcd for C42H62NO8,708.4475)。
Bistrochelide B (compound 4): white amorphous powder；Optical activity(c 3.0,
MeOH)；Electronic circular dichroism ECD (MeOH, c 4.3 × 10-4)λmax(Δ ε)=207 (+24.1), 233 (- 8.9) nm；Ultraviolet suction
Receive data UV (MeOH) λmax(logε)204(4.11),240(3.65)nm；Infrared absorption data IR (film) νmax=3419,
2934,1963,1736,1439,1378,1240,1025cm-1.1H and13CNMR data are shown in Table 1-3；High resolution mass spectrum HRESIMS
[M+H]+m/z:691.4209(calcd for C42H59O8,691.4204)。
Bistrochelide C (compound 5): white amorphous powder；Optical activity(c 1.7,
MeOH)；Electronic circular dichroism ECD (MeOH, c 4.3 × 10-4)λmax(Δ ε)=205 (+30.3), 231 (- 10.7) nm；It is ultraviolet
Absorb data UV (MeOH) λmax(logε)202(3.77)nm；Infrared absorption data IR (film) νmax=3451,2930,1762,
1735,1709,1686,1453,1241cm-1.1H and13CNMR data are shown in Table 1-3；High resolution mass spectrum HRESIMS [M+H]+m/z:
693.4359(calcd for C42H61O8,693.4361)。
Bistrochelide D (compound 6): white amorphous powder；Optical activity(c 1.1,
MeOH)；Electronic circular dichroism ECD (MeOH, c 2.0 × 10-4)λmax(Δ ε)=216 (+11.9), 254 (- 3.3) nm；Ultraviolet suction
Receive data UV (MeOH) λmax(logε)201(3.83)nm；Infrared absorption data IR (film) νmax=3436,2927,1759,
1737,1712,1687,1444,1240cm-1.1H and13C NMR data is shown in Table 1-3；High resolution mass spectrum HRESIMS [M+NH4]+m/
z:710.4630(calcd for C42H64NO8,710.4626)。
Bistrochelide E (compound 7): white amorphous powder；Optical activity(c 1.4,
MeOH)；Electronic circular dichroism ECD (MeOH, c 5.8 × 10-4)λmax(Δ ε)=205 (+17.3), 234 (- 2.9), 259 (-
0.5),304(-5.1)nm；UV absorption data UV (MeOH) λmax(logε)202(3.84)nm；Infrared absorption data IR
(film)νmax=3454,2930,1766,1738,1698,1454,1379,1230cm-1.1H and13C NMR data is shown in Table 1-3；
High resolution mass spectrum HRESIMS [M+Na]+m/z:671.3930(calcd for C40H56NaO7,671.3918)。
Table 1.Glaucumolide A-B and bistrochelide A-B's (compound 1-4)1H NMR(CDCl3,
500MHz) data
Table 2.bistrochelide C-E's (compound 5-7)1H NMR(CDCl3, 500MHz) and data
Table 3.Glaucumolide A-B and bistrochelide A-E's (compound 1-7)13C NMR(CDCl3,
125MHz) data
Embodiment 3: compound Glaucumolide A-B and bistrochelide A-E immunoregulatory activity
The splenocyte (2 × 106 cells/ml) for picking up from C57BL/6 mouse adds compound incubation for 24 hours, with sword bean ball egg
White A (Con A) is used as positive control (5 g/ milliliters of μ).Cell is collected, PBS washing passes through FACScan fluidic cell immediately after
Instrument detects Apoptosis (BD, the U.S.).Influence of the compound to the differentiation of T cell subgroup is studied, splenocyte adds compound incubation
It uses for 24 hours, ConA compound collects cell as positive control, uses PE-CD3, FITC-CD4 and percp/cy5.5-CD8 respectively
Dyeing.The percentage of CD3+, CD4+T and CD8+T cell uses flow cytometry analysis.Data result is with average value ± S.D. (n
=3) it presents.* p < 0.05, * * < 0.01, if blank control group.
Using flow cytometry to compound 1-7 (i.e. compound glaucumolide A-B and bistrochelideA-
E it) carries out ion vitro immunization and adjusts determination of activity, it is right using the activated splenocytes of concanavalin A (Con A) induction as the positive
According to these compounds are also tested the cells apoptosis of mouse boosting cell, as a result, it has been found that compound is by 3 μM of concentration
Under there is very low cytotoxicity (referring to Figure 1) to the splenocyte of test.Under the conditions of 3 μm, with flow cytomery CD3
The percentage and CD4+/CD8+ ratio of+cell, using concanavalin A as positive control (5 μ g/ml).As a result, it has been found that compound
Glaucumolide A and bistrochelide B can significantly induce CD3+T cell Proliferation (referring to Fig. 2).Compound
Glaucumolide A and bistrochelide C significantly increase CD4+/CD8+ ratio, and compound bistrochelide A is then
Reducing CD4+/CD8+ ratio reduces (referring to Fig. 3).
It is above-mentioned the experimental results showed that, tetraterpenes compound provided by the invention have certain T cell hypotype regulation activity,
And there is lower cytotoxicity, therefore can be used for preparing immunoregulation drug.The present invention provides guide to develop new drug
Compound opens new approach to further investigate and developing new drug, is conducive to develop and use Ocean Medicinal resource.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of tetraterpenes compound, which is characterized in that indicated by one of following chemical structural formula:
2. a kind of tetraterpenes compound as described in claim 1 is preparing the application in immunoregulation medicament.
3. a kind of preparation method of tetraterpenes compound as described in claim 1 characterized by comprising
S1 is provided and is crushed disk meat sesame soft coral；
The disk meat sesame soft coral methanol and/or acetone extraction of the crushing are obtained first after the concentration of gained extracting solution by S2
Medicinal extract；
First medicinal extract is suspended in water, and is extracted with ether by S3, obtains ether extraction liquid, and the ether extraction liquid is dense
The second medicinal extract is obtained after contracting；
Second medicinal extract is suspended in methanol aqueous solution by S4, and with n-hexane extraction, will be by after the n-hexane extraction
Third medicinal extract is obtained after methanol aqueous solution concentration；
S5, by the third medicinal extract carry out silica gel column chromatography separation, using the mixed solution of methylene chloride and methanol as mobile phase into
Row gradient elution successively obtains fraction 1 to fraction 14；And
Fraction 7 of the fraction 1 into fraction 14 is carried out glucose gel chromatography, with the mixed solution of methanol and chloroform by S6
It is eluted for mobile phase, successively obtains fraction 71 to fraction 77, by fraction 73 of the fraction 71 into fraction 77 with efficiently
Liquid chromatogram is isolated and purified, and obtains compound bistrochelide E, bistrochelide C and compound respectively
bistrochelide D；And/or
Fraction 8 of the fraction 1 into fraction 14 is subjected to glucose gel chromatography, is stream with the mixed solution of methanol and chloroform
Dynamic phase is eluted, and successively obtains fraction 81 to fraction 85, fraction 84 of the fraction 81 into fraction 85 is used efficient liquid phase
Chromatography is purified, and obtains compound glaucumolide A, compound glaucumolide B, compound respectively
Bistrochelide B and compound bistrochelide A.
4. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that in the step S5, with
The mixed solution of methylene chloride and methanol is that the step of mobile phase carries out gradient elution includes:
In the mixed liquor for making the methylene chloride and methanol, the volume ratio of the methylene chloride and the methanol is from 100:1 to 1:1
Carry out gradient elution.
5. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that the methanol and chloroform it is mixed
Closing the volume ratio of methanol and chloroform in liquid is 1:1.2 to 1.2:1.
6. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that the fraction 7 and/or described
The glucose gel chromatography of fraction 8 is carried out using Sephadex LH-20 gel column.
7. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that first in the methanol aqueous solution
The content of alcohol is 80wt% to 95wt%.
8. the preparation method of tetraterpenes compound according to claim 7, which is characterized in that first in the methanol aqueous solution
The content of alcohol is 90wt%.
9. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that will be described in the step S2
The step of disk meat sesame soft coral methanol and/or acetone extraction of crushing includes:
The disk meat sesame soft coral of the crushing is multiple with acetone ultrasonic extraction, obtain acetone extract, again with methanol ultrasound
It extracts repeatedly, obtains methanol extract liquid, merge the acetone extract and the methanol extract liquid, obtain the extracting solution.
10. the preparation method of tetraterpenes compound according to claim 3, which is characterized in that by the fraction 73 or institute
When stating fraction 84 and being isolated and purified with high performance liquid chromatography, acetonitrile solution that mobile phase used is 70%~80%.
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