CN107033221A - Two small-molecular peptides and preparation method thereof and the application in antiviral drugs is prepared - Google Patents
Two small-molecular peptides and preparation method thereof and the application in antiviral drugs is prepared Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
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- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
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Abstract
Application the invention discloses two small-molecular peptides and preparation method thereof and in antiviral drugs is prepared.Shown in the structure such as formula (I) of two described small-molecular peptides.Isolated new cyclic pentapeptide compound Aspergillpeptide D, the linear peptide compounds Aspergillpeptide E, the research available for antiviral lead compound with the anti-virus activities of HSV 1 in the zymotic fluid of the Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO.M 2012397 of the invention that grown nonparasitically upon another plant altogether from one plant of gorgonian.
Description
Technical field：
The invention belongs to marine organisms field, and in particular to a cyclic pentapeptide compound and a linear peptide compounds and its
Preparation method and the application in anti-HSV-1 virus drugs are prepared.
Background technology：
Living marine resources are enriched, and metabolite type is various, and structure is novel, has preferable bioactivity, is in recent years
The focus of researcher.Peptides are the big types in marine organism metabolite, the ocean peptides tool having now been found that
There are cell toxicant, antibacterial, fouling resistance isoreactivity, it is another kind of that there is neuropharmacology activity, the Peptide toxin Ziconotide of such as cone shell
It is first marine drug (trade name Prialt) with analgesic activity, is used as chronic pain caused by treatment spinal cord injury
Bitterly.In the secondary metabolite of marine microorganism, peptides also occupy important ratio, the metabolite of marine bacteria
What it is more than 56% is peptides.
Spore exanthema virus belongs to the member of spore exanthema virus family, and with α, three types of beta, gamma, wherein HSV-1S belongs to α types.
HSV clinical manifestation is multifarious, generally mild or symptomless infection, but neonate and immunocompromised person can cause seriously
Infection.HSV-1 is mainly infected by respiratory tract, skin and mucous membrane close contact, causes lip, pharynx, eye and skin infection, few
It is several, cause genital infection.After essential spore rash infects, hidden in the hiding and trigeminal neuralgia (HSV- because the virus of its remaining is long-term
1), such as generate heat when the reduction of body body drag or some excitation conditions, suffer from cold, infect and can cause recurrent infection.
Main nucleoside medicine treatment gebitalis virus clinical at present infects, it is adaptable to HSV- primary and recurrence
Sexuality dye, then hard to work to incubation period, conventional medicine is mainly ACV and its similar medicine, and selectivity is high, aligns
Normal cytotoxicity is small, but long-term use has certain side effect, causes contact dermatitis etc., produces resistance Zhu, therefore, exploitation profit
With new resource, seek preferably anti-HSV medicines imperative.
The content of the invention：
First purpose of the present invention is to provide a new cyclic pentapeptide compound with anti-HSV-1 virus activities
An Aspergillpeptid e D and new linear peptide compounds Aspergillpeptide E.
The new cyclic pentapeptide compound of the present invention and a new linear peptide compounds, its structural formula such as formula (I) institute
Show,
Wherein compound 1：It is named as Aspergillpeptide D；Compound 2：It is named as Aspergillpeptide
E。
Cyclic pentapeptide compound Aspergillpeptide D, the linear peptide compounds Aspergillpeptide E of the present invention
It is prepared by the following method, this method comprises the following steps：
(a) Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO are prepared：M 2012397 zymotic fluid；
(b) the zymotic fluid macroporous resin adsorption for obtaining step (a), then rinses macroreticular resin with water and removes culture medium
Composition, again with methanol or alcohol flushing macroreticular resin obtain methanol or ethanol extract；Also the zymotic fluid that step (a) can be obtained
Extracted with ethyl acetate, dichloromethane or chloroform solvent, be concentrated to give ethyl acetate extract, dichloromethane extract or chloroform
Extract；
(c) by step (b) methanolic extract, ethanol extract, ethyl acetate extract, dichloromethane extract or
Chloroform extract passes through normal-phase silica gel column chromatography, be respectively successively 100% with dichloromethane and methanol volume ratio, 90%,
80%th, 70%, 60% and 50% methylene chloride-methanol system gradient elution, collection respectively is with methylene chloride volume fraction
90% and 60% methylene chloride-methanol is the eluant, eluent component A, the B that rinse, the two components respectively through silicagel column with
Gel filtration chromatography obtains crude product, is purified through HPLC, respectively obtains compound Aspergillpeptide D and compound
Aspergillpeptide E。
Zymotic fluid described in step (a) can be prepared by the following method：By Aspergillus Aspergillus sp.SCSGAF
0076CCTCC NO：M 2012397 is inoculated into the applicable culture medium of aspergillus fungi, is made under common fermentation condition,
It is preferred that preparation method be by Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO：M 2012397 is in aspergillus
Grown in the applicable plating medium of fungi, after fungi grows spore, fungi is up to filled to the three of water with bamboo stick from flat board
In the bottle of angle, fungi liquid is inoculated into culture medium and (300ml culture mediums is filled in 1L triangular flasks) with liquid-transfering gun, in being stored at room temperature training
Support 30 days, obtain zymotic fluid, described culture medium is：Every liter of 20g containing sorbierite, yeast extract 3g, MgSO4·7H2O 0.3g, taste
Smart 10g, tryptophan 2g, KH2PO40.5g, maltose 20g, sea salt 30g, methanol 5ml, surplus are water, pH 6.5.
Concentration described in step (b), which is used, to be concentrated under reduced pressure.
Cyclic pentapeptide compound Aspergillpeptide D, the linear peptide compounds Aspergillpeptide E of the present invention
Find that they have anti-HSV-1 virus activities, its IC through experiment50Value is respectively 9.5,19.8 μM；And compound
Aspergillpeptide D can also suppress ACV antibody-resistant bacterium HSV-1-106 and HSV-1-153 in 12.5 μM of concentration
Caused cytopathy, inhibiting rate about 50%.
Thus third object of the present invention is to provide ring thing peptide compounds aspergillpeptide D or linear peptides
Applications of the compound aspergillpeptide E in antiviral drugs is prepared.
Described antiviral drugs is preferably anti-HSV-1 virus drugs.
A kind of antiviral drugs, it is characterised in that contain compound Aspergillpeptide D or compound
Aspergillpeptide E are used as active component.
Fourth object of the present invention is to provide Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO：M
2012397 are preparing a cyclic pentapeptide compound Aspergillpeptide D and linear peptide compounds Aspergillpeptide
Application in E.
The present invention grows nonparasitically upon another plant Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO altogether from one plant of gorgonian：M
The isolated two new cyclic pentapeptide compounds with anti-HSV-1 virus activities in 2012397 zymotic fluid
Aspergillpeptide D, linear peptide compounds Aspergillpeptide E, these compounds have anti-HSV-1 viruses living
Property, the lead compound of the antibiotic with anti-HSV-1 viruses can be developed into.
The Aspergillus sp.SCSGAF 0076 of the present invention, Chinese Typical Representative culture is preserved on October 11st, 2012
Thing collection (CCTCC), address：Wuhan, China Wuhan University, its deposit number is：CCTCC NO：M 2012397, the bacterium
Plant and be disclosed in the patent No.：ZL 201210431886.6, denomination of invention：One class cycle tetrapeptide compound and preparation method thereof and system
In the patent of application in standby fouling resistance agent.
Embodiment：
Following examples are that the present invention is further illustrated, rather than limitation of the present invention.
Embodiment 1：
By sorbierite 20g, yeast extract 3g, MgSO4·7H2O 0.3g, monosodium glutamate 10g, tryptophan 2g, KH2PO40.5g, wheat
Bud sugar 20g, methanol 5ml, sea salt 30g mixing, with water constant volume to 1L, pH is to 6.5 for regulation, obtains 1L culture mediums, in this manner
Configure culture medium.In the conical flask that the culture medium is fitted into about 330 1000mL, every bottle of about 300mL steams in 115 DEG C of high pressures
Vapour sterilizes 25 minutes.
By Aspergillus Aspergillus sp.SCSGAF 0076CCTCC NO：M 2012397 is applicable in aspergillus fungi
Plating medium in grow, after fungi grows spore, with bamboo stick by fungi from moved on flat board fill water triangular flask in,
Fungi is inoculated into culture medium and (300ml culture mediums is filled in 1L triangular flasks) with liquid-transfering gun, in room temperature (26 DEG C) quiescent culture
After 30 days, zymotic fluid is collected.
The zymotic fluid 100L macroporous resin adsorptions that will be obtained through above-mentioned medium culture, then rinse macroreticular resin with water
Remove medium component, then macroreticular resin is rinsed with ethanol (can also use methanol) and obtain ethanol extract, (zymotic fluid can also use second
Acetoacetic ester, dichloromethane or chloroform extraction), it is concentrated under reduced pressure to give alcohol extracts 85g.Alcohol extracts purification on normal-phase silica gel
(100-200 mesh) dry method is mixed after sample, loads glass chromatography column (the thin silica gel of H), normal temperature reduced pressure chromatography uses dichloromethane body successively
(methanol ratio is or not the methylene chloride-methanol system gradient elution that fraction is 100%, 90%, 80%, 70%, 60%, 50%
It is disconnected to increase), each flow point is merged according to thin-layer chromatography situation, eluting solvent is reclaimed, is evaporated flow point and is shifted with methanol.Collect respectively
It is the component A, B that eluant, eluent is rinsed with the methylene chloride-methanol that methanol volume fraction is 90% and 60%.Component A is frequent
Silica gel column chromatography separation (diameter 3cm, column length 60cm, containing the thin silica fillers of H) is pressed, with chloroform/methanol (v/v 100:0-50:50)
For eluting solvent system, gradient elution obtains 5 small components, wherein with chloroform/methanol (v/v 90:10) component afforded
Inverted silica gel dry method is mixed after sample, loads glass chromatography column (diameter 5cm, column length 50cm, containing anti-phase Rp-18 fillers), normal temperature subtracts
Pressure column chromatography, successively with water-first that methanol volume fraction is 10%, 30%, 40%, 50%, 60%, 70%, 85% and 100%
Alcohol system gradient elution (methanol ratio is continued to increase), collects the component that methanol volume fraction is 60%, by gel (diameter
10mm, column length 1600mm, gel are sephedexLH-20, and mobile phase is volume ratio 1:1 methanol-chloroform), obtain crude product, crude product
Using efficient liquid phase preparative separation, Detection wavelength is 280nm, and flow velocity is 5mL/min, and mobile phase is methanol-water (v/v 47:
53), chromatographic column is phenomenex Gemini 10mm × 250mm, obtains (the t of compound 1R=27.0min).Component B is through just
The phase silica gel column chromatography dichloromethane that use methylene chloride volume fraction is 100%, 90%, 80%, 70%, 60%, 50% successively-
Methanol system gradient elution, collects the component that methylene chloride volume fraction is 80% elution, then using reversed phase chromatography column chromatography according to
Secondary use methanol volume fraction is 10%, 30%, 40%, 50%, 60%, 70%, 85% and 100% water-methanol system gradient
Elute (methanol ratio is continued to increase), collect the component that methanol volume fraction is 45% elution, using efficient liquid phase preparative separation,
Detection wavelength is 280nm, and flow velocity is 5mL/min, and mobile phase is acetonitrile-water (v/v 72:28), chromatographic column is phenomenex
Gemini 10mm × 250mm, obtain (the t of compound 2R=30.0min)
Structure is estimated：
Compound 1,1H and13C H NMR spectroscopies data as shown in table 1, are provided by high resolution mass spectrum (HRESIMS) at m/z
Quasi-molecular ion peak 728.3680 [M+H]+, with reference to NMR spectra data, the molecular formula for learning compound is C40H49N5O8。13C
H NMR spectroscopy, which is shown in low field area, the carbon signal (δ of 5 acid amides or ester carbonyl groupC168.4,169.0,169.6,170.2,170.5),
There is α-C signal (δ of 5 amino acid in high field regionC49.2,55.4,55.4,60.7,62.0),1H H NMR spectroscopies show 3 acyls
Amine proton signal (δH8.63,6.99,6.63), this illustrates that the compound is a cyclic peptide compound.Pass through HSQC, HMBC
And H-H COSY signals, it is known that the compound contains 2 oxygen methyl-tyrosines (O-Me-Tyr), N-methyl tyrosine (N-Me-
Tyr), proline (Pro), valine (Val), further by HSQC, HMBC and H-H COSY, it is presumed that going out the chemical combination
The connected mode of thing amino acid fragment is Val- (N-Me-) Tyr- (O-Me-) Tyr- (O-Me-) Tyr-Pro, determines the compound
Planar structure such as formula (I) show.
The absolute configuration of compound 1 is determined by Marfey reactions.Basic skills：1. compound hydrolysis.Weigh this
Compound 0.5mg is dissolved in 1ml 6N HCl, 17 hours under the conditions of 115 DEG C, and cooling is dissolved in 100ul water after being evaporated；②
Marfey reacts.In 100ul water sample samples, plus 1M NaHCO320ul, FDAA (1%, acetone solution) 100ul, 40 DEG C of conditions
Lower 1 hour, after cooling, 20ul 2M HCl are added, methanol is dissolved in after being evaporated；3. HPLC is analyzed.With 15%-45% acetonitrile/water
Gradient elution is carried out, 0.04%TFA, flow velocity 1.0ml/min, Detection wavelength 340nm, analysis chromatographic column are wherein contained in aqueous phase
For YMC-Pack ODS-A column (250 × 10mm).Standard items D-Ala, L-Ala, D-Pro, L-Pro, N-Me-D-Tyr,
N-Me-L-Tyr, O-Me-D-Tyr, O-Me-L-Tyr, carried out with same method it is above-mentioned 2., 3. handle.Eventually through relatively more anti-
The FDAA derivatives and standard items FDAA derivatives of thing is answered to be defined as L-Val, N-Me-D-Tyr in the HPLC retention times analyzed,
O-Me-L-Tyr, and L-Pro (as formula I is shown), thereby determine that the structural formula of compound 1 as shown in 1 in formula (I), compound 1
It is named as Aspergillpeptide D.
Compound 2,1H and13C H NMR spectroscopies data as shown in table 2, are provided by high resolution mass spectrum (HRESIMS) at m/z
Quasi-molecular ion peak 467.2296 [M+H]+, with reference to NMR spectra data, the molecular formula for determining compound is C25H30N4O5。13C
H NMR spectroscopy, which is shown in low field area, the carbon signal (δ of 3 acid amides or ester carbonyl groupC161.9,171.9,173.5),1H H NMR spectroscopies are shown
Go out 3 amide proton signal (δH8.78,8.63,10.85), this illustrates that the compound is a peptides, passes through
HSQC, HMBC and H-H COSY signals, thus it is speculated that the compound includes 3 amino acid fragments, respectively valine (Val), junket
Propylhomoserin (Tyr) and tryptophan (Trp).Further by HMBC coherent signals, NH-Val (δH8.63) with C=O-Trp (δC
171.9) it is related, NH-Trp (δH8.78) with C=O-Tyr (δC161.9) it is related, so that it is determined that the row of the compound amino acid
Row mode is Tyr-Trp-Val, determines that the planar structure such as formula (I) of the compound is shown.
The absolute configuration of compound 2 is determined by above-mentioned identical Marfey reactions.After compound hydrolysis, standard items
D-Val, L-Val, D-Tyr, L-Tyr, D-Trp, L-Trp are handled with identical method, eventually through comparing reactant
FDAA derivatives and standard items FDAA derivatives are defined as D-Val, D-Tyr in the HPLC retention times analyzed.In compound
Tryptophan is after hydrolysis, and HPLC does not detect tryptophan, because L-type tryptophan as precursor substance is added to culture medium
In, so it is presumed that 2 institutes being configured as in L-Trp, the structural formula such as formula (I) of compound 2 of the tryptophan in the compound
Show, compound 2 is named as Aspergillpeptide E.
Table 1：Compound 11H and13C data (500,125MHz, DMSO-d6,δppm)
Table 2：Compound 21H and13C data (500,125MHz, DMSO-d6,δppm)
Embodiment 2：The peptides Aspergillpeptide D of ring five, linear peptide compounds Aspergillpeptide
E anti-HSV-1 virus activities test
Sample is observed by using mtt assay to survey the cytotoxicity and cytopathic effect method (CPE methods) of Vero cells
Test agent is to herpes simplex virus (HSV-1 15577) bacterial strain, ACV antibody-resistant bacterium HSV-1-106 and ACV
The inhibitory action of antibody-resistant bacterium HSV-1-153 institutes cytopathogenic effect, understand Aspergillpeptide D and
Aspergillpeptide E anti-herpes simplex virus I-form (HSV- I) effect.Cytopathic effect method is summarized as follows：(1)
Vero cells are with 1.5*105Individual/ml is inoculated in 96 porocyte culture plates, 100ug/ holes, puts 37 degree, 5%CO2, cultivate 24h length
Into individual layer.(2) grown cultures liquid is abandoned, by the peptides compound a spergillpeptide D of ring five, the linear peptides of various concentrations
Compound aspergillpeptide E and HSV-1 viral dilution liquid (100TCID50) cell monolayer is added to after isometric mixing, often
Individual concentration sets 4 multiple holes, while setting positive drug ACV (ACV) control group, normal cell controls group and virus control group.
(3) 37 DEG C, 5%CO2Continue to cultivate 48h.(4) after 48h, light Microscopic observation, record cytopathic effect (CPE).Cytopathy
Degree evaluation：0~25% for+, 26%~50% is ++, 51%~75% is +++, 76%~100% is ++++.Detailed Experimental
Method bibliography (J.Ethnopharm.2002,79,205-211) is described.
Experimental result shows, cytotoxic activity test show compound Aspergillpeptide D and
Aspergillpeptide E suppress the maximal non-toxic concentration TC of host's Vero cell growths0Respectively 81.9,153.2 μM；
Under their maximal non-toxic concentration, the anti-HSV-1 viruses of compound Aspergillpeptide D and Aspergillpeptide E
IC50Value is respectively 9.5,19.8 μM；In addition, compound Aspergillpeptide D can also suppress in 12.5 μM of concentration Ah
Cytopathy caused by VCV antibody-resistant bacterium HSV-1-106 and HSV-1-153, inhibiting rate about 50%.Positive control Ah former times Lip river
The IC of the anti-HSV-1 viruses of Wei50It is worth for 3.0 μM, suppresses the maximal non-toxic concentration TC of host's Vero cell growths0For>1000μM.Though
Right Aspergillpeptide D and Aspergillpeptide E anti-HSV-1 virus activities are not so good as ACV, but they
The nucleoside compound of ACV series is not belonging to, mechanism of action will be different from ACV, and compound
Aspergillpeptide D also have better inhibition effect to ACV antibody-resistant bacterium HSV-1-106 and HSV-1-153.Thus
It can be seen that Aspergillpeptide D, Aspergillpeptide E have preferable anti-HSV-1 virus activities.
Claims (9)
1. small-molecule peptide compound, its structural formula as shown in compound 1 or compound 2 in formula (I),
Wherein compound 1 is compound Aspergillpeptide D, and compound 2 is compound Aspergillpeptide E.
2. compound Aspergillpeptide D and compound Aspergillpeptide E described in a kind of claim 1
Preparation method, it is characterised in that this method comprises the following steps：
(a) the CCTCC NO of Aspergillus Aspergillus sp.SCSGAF 0076 are prepared：M 2012397 zymotic fluid；
(b) the zymotic fluid macroporous resin adsorption for obtaining step (a), then with water rinse macroreticular resin remove culture medium into
Point, again with methanol or alcohol flushing macroreticular resin obtain methanol or ethanol extract；Or the zymotic fluid second for obtaining step (a)
Acetoacetic ester, dichloromethane or chloroform solvent extraction, are concentrated to give ethyl acetate extract, dichloromethane extract or chloroform recovery
Thing；
(c) by step (b) methanolic extract, ethanol extract, ethyl acetate extract, dichloromethane extract or chloroform
Extract passes through normal-phase silica gel column chromatography, be respectively successively 100% with dichloromethane and methanol volume ratio, 90%, 80%,
70%th, 60% and 50% methylene chloride-methanol system gradient elution, collection methylene chloride volume fraction is 90% He respectively
60% methylene chloride-methanol is component A, the B that eluant, eluent is rinsed, and the two components are respectively through silicagel column and gel column
Chromatography obtains crude product, is purified through HPLC, respectively obtains compound Aspergillpeptide D and compound
Aspergillpeptide E。
3. preparation method according to claim 2, it is characterised in that the zymotic fluid described in step (a) is by following
It is prepared by method：By the CCTCC NO of Aspergillus Aspergillus sp.SCSGAF 0076：M 2012397 is suitable in aspergillus fungi
Grow, after fungi grows spore, scraped fungi into the triangular flask being filled with water from flat board with bamboo stick in plating medium,
Fungi is inoculated into culture medium with liquid-transfering gun, in being stored at room temperature culture 30 days, zymotic fluid is obtained, described culture medium is：Often
Rise 20g containing sorbierite, yeast extract 3g, MgSO4·7H2O 0.3g, monosodium glutamate 10g, tryptophan 2g, KH2PO40.5g, maltose
20g, sea salt 30g, methanol 5ml, surplus are water, pH 6.5.
4. preparation method according to claim 2, it is characterised in that the concentration described in step (b), which is used, to be concentrated under reduced pressure.
5. the compound Aspergillpeptide D or compound Aspergillpeptide E described in claim 1 are in system
Application in standby antiviral drugs.
6. application according to claim 5, it is characterised in that described antiviral drugs is the medicine of anti-HSV-1 viruses.
7. a kind of antiviral drugs, it is characterised in that contain the compound Aspergillpeptide D described in claim 1
Or compound Aspergillpeptide E are used as active component.
8. antiviral drugs according to claim 7, it is characterised in that described antiviral drugs is anti-HSV-1 viruses
Medicine.
9. the CCTCC NO of Aspergillus Aspergillus sp.SCSGAF 0076：M 2012397 is in prepare compound
Application in Aspergillpeptide D or compound Aspergillpeptide E.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993269A (en) * | 2012-11-01 | 2013-03-27 | 中国科学院南海海洋研究所 | Cyclo-tetrapeptide compounds, preparation method thereof and application of cyclo-tetrapeptide compounds in preparation of anti-fouling agent |
| CN103265550A (en) * | 2013-04-17 | 2013-08-28 | 中国科学院南海海洋研究所 | Alkaloid compound, preparation method thereof, application thereof in preparing paints resisting marine biofouling and anticancer drugs |
| CN105384727A (en) * | 2015-10-10 | 2016-03-09 | 中国科学院南海海洋研究所 | Tetramic acid compound and preparation method thereof, and application of tetramic acid compound in preparing anti-tumor and anti-viral drugs |
-
2017
- 2017-02-08 CN CN201710069098.XA patent/CN107033221A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993269A (en) * | 2012-11-01 | 2013-03-27 | 中国科学院南海海洋研究所 | Cyclo-tetrapeptide compounds, preparation method thereof and application of cyclo-tetrapeptide compounds in preparation of anti-fouling agent |
| CN103265550A (en) * | 2013-04-17 | 2013-08-28 | 中国科学院南海海洋研究所 | Alkaloid compound, preparation method thereof, application thereof in preparing paints resisting marine biofouling and anticancer drugs |
| CN105384727A (en) * | 2015-10-10 | 2016-03-09 | 中国科学院南海海洋研究所 | Tetramic acid compound and preparation method thereof, and application of tetramic acid compound in preparing anti-tumor and anti-viral drugs |
Non-Patent Citations (2)
| Title |
|---|
| XUAN MA ET AL.: "Antiviral peptides from marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501", 《TETRAHEDRON LETTERS》 * |
| 农旭华等: "柳珊瑚共附生真菌Aspergillus terreus SCSGAF0162 中土震素和丁内酯类化合物的研究", 《中国化学会第十届全国天然有机化学学术会议论文集》 * |
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