CN110357864A - A kind of pyrroles's sesquiterpenoids and its preparation method and application - Google Patents
A kind of pyrroles's sesquiterpenoids and its preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of pyrroles's sesquiterpenoids and its preparation method and application, belong to field of medicaments.This pyrroles's sesquiterpenoids structure novel, and there is immunosuppressive action, it can be used for preparing immunosuppressor, have a extensive future.The general structure of this pyrroles's sesquiterpenoids is as follows:
Description
Technical field
The present invention relates to field of medicaments, in particular to a kind of pyrroles's sesquiterpenoids and preparation method thereof and
Purposes.
Background technique
T lymphocyte activation, proliferation and differentiation are most important to the immune response of host, their function needs stringent
Control, to ensure that corresponding immune response is in suitable control range.The T lymphocyte proliferation of disorder can lead to many itself
Immunity disease, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, psoriasis etc..Immunosuppressor
Such as rapamycin, cyclosporin, tacrolimus, mycophenolate are often widely used in this kind of disease for the treatment of.However, pathogen
There is significant otherness for different patients with drug susceptibility.During treatment, if the effect of monotherapy
It is unobvious, then to use conjoint therapy, sequential therapy etc..Therefore, we there is an urgent need to research and develop more immunosuppressor to help
Help those sufferers insensitive to previous therapy.
Miscellaneous terpene natural products is distributed widely in bacterium, fungi, marine organisms and higher plant, they are terpenoids
The hybrid products of object and other kinds of natural products.It is in recent years, more and more about the research report of miscellaneous terpene natural products,
Miscellaneous terpenoid already becomes a hot spot in Natural products research field, they or there is diversified novel chemistry knot
Structure, or certain significant bioactivity can be shown.At present, it has been reported that miscellaneous terpene chemical structure quantity well below nature
The potential output in boundary.Therefore, miscellaneous terpene natural products is studied, especially to those researchs report less hypotype into
The excavation of the double-depth of row chemical structure and bioactivity is of great advantage.
Summary of the invention
The purpose of the present invention is to provide a kind of pyrroles's sesquiterpenoids and its preparation method and application, and the present invention mentions
This pyrroles's sesquiterpenoids structure novel supplied, and there is immunosuppressive action, it can be used for preparing immunosuppressor, answer
With having a extensive future.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of pyrroles's sesquiterpenoids, structural formula is as shown in general formula I:
In formula, C11-R1Selected from by substituted or unsubstituted C4~10Alkane, substituted or unsubstituted cycloalkane, substitution or not
The group of at least one of substituted heterocycloalkane composition；
R2Selected from OH or H；
It is expressed as singly-bound or double bond.
Further, in preferred embodiments of the present invention, above-mentioned R1Selected from by substituted or unsubstituted C4~10Alkane takes
The group of at least one of generation or unsubstituted pentamethylene, substituted or unsubstituted tetrahydrofuran composition.
Further, in preferred embodiments of the present invention, work as C7-C8-C9-C10Between when being singly-bound, C8With C11Between
Form C8-O-C11Key, R1Structure it is as follows:
Further, in preferred embodiments of the present invention, work as C7-C8-C9-C10Between only a double bond and be located at
C8-C9Between when, C11-R1Structure it is as follows:
Further, in preferred embodiments of the present invention, work as C7With C8Between be double bond when, C11-R1Selected from by following base
The group of group's composition:
Further, in preferred embodiments of the present invention, above-mentioned pyrroles's sesquiterpenoids, for following number 1~6
Any particular compound:
A kind of preparation method of above-mentioned pyrroles's sesquiterpenoids comprising:
015 strain of streptomycete Streptomyces sp.KIB is subjected to fermented and cultured, obtains culture solution；
After culture solution is extracted with ethyl acetate, total medicinal extract is obtained, total medicinal extract is isolated and purified using chromatography separation method, is obtained
To formula (I) compound；Wherein, chromatography separation method includes silica gel column chromatography, glucan Sephadex LH-20 gel column layer
Analysis, half preparative high-performance liquid chromatographic of reverse phase.
Further, in preferred embodiments of the present invention, the condition for carrying out fermented and cultured to strain is: temperature 27-33
DEG C, incubation time 8-12 days；The fluid nutrient medium that fermented and cultured is carried out to strain includes: glucose 15-25 according to parts by weight
Part, 3-8 parts of beef extract, 3-8 parts of peptone, 3-8 parts of yeast extract powder, 3-8 parts of sodium chloride, 1-5 parts of calcium carbonate.
A kind of application of above-mentioned pyrroles's sesquiterpenoids in preparation immunosuppressor.
A kind of pharmaceutical composition, active constituent include above-mentioned pyrroles's sesquiterpenoids and pharmaceutically acceptable
Auxiliary material.
Compared with prior art, the invention has the benefit that
This pyrroles's sesquiterpenoids structure novel provided by the invention, and there is immunosuppressive action, it can be used for
Immunosuppressor is prepared, the treatment of autoimmune disease is facilitated.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1: the hydrogen spectrum Chemical shift differences of 1 chirality Mosher ester of compound are analyzed and analyze chemical combination in Mosher model
The absolute configuration of C-10 carbon in 1 molecule of object.
Fig. 2: the hydrogen spectrum Chemical shift differences of 3 chirality Mosher ester of compound are analyzed and analyze chemical combination in Mosher model
The absolute configuration of C-10 carbon in 3 molecule of object.
Fig. 3: the calculating of compound 4 and actual measurement electronic circular dichroism figure.
Fig. 4: the calculating of compound 5 and actual measurement electronic circular dichroism figure.
Fig. 5: the calculating of compound 6 and actual measurement electronic circular dichroism figure.
Fig. 6: the compound 1-6 inhibiting effect that the human T-cell that dual anti-(anti-CD3/anti-CD28) is activated is proliferated
IC50Value.
Fig. 7: compound 1-6 is proliferated the human T-cell of phytohemagglutin phytolectin (phytohemagglutin, PHA) induced activation
Inhibiting effect IC50Value.
Fig. 8: compound does not inhibit the activation of T cell, it, which is generated by the retardance activating T cell period in the G0/G1 phase, exempts from
Epidemic disease inhibiting effect.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
In a first aspect, present embodiment provides a kind of pyrroles's sesquiterpenoids, structural formula is as shown in general formula I:
In formula, C11-R1Selected from by substituted or unsubstituted C4~10Alkane, substituted or unsubstituted cycloalkane, substitution or not
The group of at least one of substituted heterocycloalkane composition；
R2Selected from OH or H；
It is expressed as singly-bound or double bond.
Further, above-mentioned R1Selected from by substituted or unsubstituted C4~10Alkane, substituted or unsubstituted pentamethylene, substitution
Or the group of at least one of unsubstituted tetrahydrofuran composition.
Further, work as C7-C8-C9-C10Between when being singly-bound, C8With C11Between form C8-O-C11Key, R1Structure
It is as follows:
According to the convention of the art, used in structural formula hereFor describe group part or substituent group with
The key of core or backbone structure junction.
Further, work as C7-C8-C9-C10Between only a double bond and be located at C8-C9Between when, C11-R1Structure such as
Under:
Further, work as C7With C8Between be double bond when, C11-R1Selected from the group being made of following groups:
Further, compound shown in formula I any particular compound described in number 1~6 as follows:
In the present invention, use is defined below:
“C4~10Alkyl " refers to the linear chain or branched chain one of 4~10 saturations and/or unsaturated carbon atom and hydrogen atom composition
Valence residue, such as butyl (Bu), isobutyl group, tert-butyl (t-Bu), pentenyl, cyclobutenyl, butynyl, pentynyl, hexin base etc.,
It can be unsubstituted or is selected from as replaced undefined substituent group by one or more identical or different.
" naphthenic base " refers to the non-aromatic monovalence list for containing 3,4,5,6,7,8,9,10,11,12,13 or 14 carbon atoms
Ring, bicyclic or tricyclic residue, every kind can be saturated or unsaturated, and can be unsubstituted or one or more
Replaced the identical or different substituent group defined selected from the present invention.
" Heterocyclylalkyl " refers to non-aromatic contain 3,4,5,6,7,8,9,10,11,12,13 or 14 carbon atoms one
Valence monocyclic, bicyclic or tricyclic residue comprising 1,2,3,4,5 or 6 identical or different miscellaneous original selected from nitrogen, oxygen and sulphur
Son.Every kind can be saturated or unsaturated, and can be unsubstituted or identical or different by one or more choosings
Replaced the substituent group defined from the present invention.
" substituent group " is halogen, carboxyl, ester group, C1~6Alkyl, alkoxy, acyl group, acylamino-, sulfonyl, sulfydryl, alkane sulphur
Base, naphthenic base, Heterocyclylalkyl, amino, alkylamino, dialkylamino, cyano, difluoromethyl, trifluoromethyl or with above-mentioned group
C1~4Alkyl.
Second aspect, present embodiment provide a kind of preparation method of above-mentioned pyrroles's sesquiterpenoids comprising with
Lower step:
Step S1: 015 strain of streptomycete Streptomyces sp.KIB is subjected to fermented and cultured, obtains culture solution；
Wherein, 015 strain of streptomycete Streptomyces sp.KIB is that document discloses strain (i.e. S.sp.KIB 015),
The document are as follows: Isolation and Biosynthesis of Labdanmycins:Four New Labdane
Diterpenes from Endophytic Streptomyces, Organic Chemistry Frontiers, 2018,5,
1272–1279。
Further, the condition for carrying out fermented and cultured to strain is: 27-33 DEG C of temperature, incubation time 8-12 days；Or it is
29-31 DEG C of temperature, incubation time 9-11 days.
Further, carry out the fluid nutrient medium of fermented and cultured to strain includes: glucose 15-25 according to parts by weight
Part, 3-8 parts of beef extract, 3-8 parts of peptone, 3-8 parts of yeast extract powder, 3-8 parts of sodium chloride, 1-5 parts of calcium carbonate.
Alternatively, the fluid nutrient medium includes: 18-23 parts of glucose according to parts by weight, and 4-6 parts of beef extract, peptone 4-6
Part, 4-6 parts of yeast extract powder, 4-6 parts of sodium chloride, 2-4 parts of calcium carbonate.
Step S2: after the culture solution is extracted with ethyl acetate, obtaining total medicinal extract, is separated using chromatography separation method pure
Change total medicinal extract, obtains formula (I) compound；Wherein, the chromatography separation method includes silica gel column chromatography, glucan
Sephadex LH-20 gel filtration chromatography, half preparative high-performance liquid chromatographic of reverse phase.
The third aspect, present embodiment provide a kind of above-mentioned pyrroles's sesquiterpenoids in preparation immunosuppressor
Using.
Inventor is studies have shown that this 6 kinds of pyrroles's sesquiterpenoids that present embodiment provides all have stronger exempt from
Epidemic disease inhibiting effect.Wherein, the most significant with the immunosuppressive action of compound 4.Compound 4 is by retardance activating T cell week
Phase generates immunosuppressive action in the G0/G1 phase.Thus illustrate, this pyrroles's sesquiterpenoids that present embodiment provides
It can be used for preparing immunosuppressor, facilitate the treatment of immune deficiency disorder.
Fourth aspect, present embodiment provide a kind of pharmaceutical composition, and active constituent includes above-mentioned pyrroles's sesquiterpenoids
Compound and pharmaceutically acceptable auxiliary material.
The pharmaceutical composition contains pharmaceutically various typical additives (such as excipient), pharmaceutical preparation is made.
According to therapeutic purposes, which can be made to various types of administration unit dosage forms, such as tablet, pill, pulvis, liquid
Body, suspension, gel, lotion, emulsifiable paste, granule, hard capsule, suppository and injection (solution and suspension, generally injection)
Deng.Preferably, the dosage form of the pharmaceutical composition is injection, for locally injecting (such as subcutaneous, nerve surrounding, joint cavity
Deng)；Alternatively, the dosage form of the pharmaceutical composition is gel, lotion, emulsifiable paste etc., part can be coated on；Alternatively, the pharmaceutical composition
Dosage form be tablet, pill, pulvis, granule, hard capsule etc., be administered orally and reach anesthesia or analgesic effect.
In order to shape the pharmaceutical composition of tablet form, it can be used this field any of and widely used figuration
Agent.For example, carrier, such as lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, avicel cellulose and silicon
Acid etc.；Adhesive, such as water, ethyl alcohol, propyl alcohol, common syrup, glucose solution, starch solution, penetrating judgment solution, carboxymethyl cellulose
Element, lac, methylcellulose and potassium phosphate, polyvinylpyrrolidone etc.；Disintegrating agent, such as dried starch, mosanom, agar powder and sea
With powder, sodium bicarbonate, calcium carbonate, the aliphatic ester of polyethylene sorbitan, lauryl sodium sulfate, stearic acid monoglycerides,
Starch and lactose etc.；Disintegration inhibitor, such as white sugar, glycerol tristearate, coconut oil and hydrogenated oil and fat；Adsorption enhancer, such as season
Amine base and lauryl sodium sulfate etc.；Wetting agent, such as glycerol, starch；Adsorbent, such as starch, lactose, kaolin, bentonite
With colloid silicic acid etc.；And lubricant, such as pure talcum, stearate, boric acid powder and polyethylene glycol etc..If necessary
Words can also use common coated material to make tablet as sugar coated tablet, painting gelatin film tablet, enteric coated tablets, film coated tablets, double
Tunic tablet and multilayer tablet.
In order to shape the pharmaceutical composition of pill, it can be used this field any of and widely used inborn nature
Agent, for example, carrier, such as lactose, starch, coconut oil, hardened vegetable oils, kaolin and talcum；Adhesive, such as gum arabic
Powder, yellow work rubber powder, gelatin and ethyl alcohol etc.；Disintegrating agent, such as agar and Kelp Powder.
In order to shape the pharmaceutical composition of suppository form, it can be used this field any known and widely used inborn nature
Agent, such as ester, gelatin and the semi-synthetic glyceride of polyethylene glycol, coconut oil, higher alcohol, higher alcohol etc..
, can be by solution and suspension liquid disinfectant in order to prepare the pharmaceutical composition of injection form, and it is preferably added suitable chlorine
Change sodium, glucose or glycerol etc., is made and the isotonic injection of blood.When preparing injection, it is possible to use in the art any
Common carrier, for example, the isooctadecanol and polyethylene of water, ethyl alcohol, propylene glycol, the isooctadecanol of ethoxylation, polyoxy
The aliphatic ester etc. of anhydro sorbitol.In addition, common lytic agent, buffer and analgesic etc. can also be added.
Pyrroles's sesquiterpenoids as shown in formula (I) of the invention and its pharmaceutically acceptable salt are in pharmaceutical composition
Content in object can be selected, generally can be mass percent 0.1~99.9% in a wide range without specifically limited,
Preferably mass percent 1~70%, more preferably mass percent 1~30%.
In the present invention, the medication of the pharmaceutical composition is not particularly limited.Can according to patient age, gender and
Other conditions and symptom select the preparation of various dosage forms to be administered.For example, tablet, pill, solution, suspension, lotion, granule
It is oral administration with capsule；Injection can carry out muscle with injection merely, inject in intradermal, subcutaneous or abdomen；Suppository is to be administered into
Rectum.
In the present invention, use can be properly selected according to method of administration, patient age, gender and other conditions and symptom
Pharmaceutical quantities.Common dosage can are as follows: about 0.01~300mg active pharmaceutical ingredient/kg body weight/day.In general, it each gives
Medicine unit dosage forms can contain the active pharmaceutical ingredient of 1~200mg.Without prejudice to the field on the basis of common sense, above-mentioned each preferred stripe
Part, can any combination to get each preferred embodiment of the present invention.
Unless otherwise indicated, term disclosed in the present invention and abbreviation have the meaning of their standards.
Feature and performance of the invention are described in further detail with reference to embodiments:
Embodiment 1
The preparation of compound 1-6 and Structural Identification:
One, preparation process:
1. fermentation condition
The configuration of seed culture fluid: it takes beef extract 6.0g, tryptone 10.0g to be dissolved in appropriate amount of deionized water, then plus goes
Ionized water is settled to 2000mL, adjusts pH to 7.0.Gained seed culture fluid is averagely dispensed into 40 250 mL baffled
In Ermlenmeyer bottles, high-temperature sterilization 30min, spare at 121 DEG C.By streptomycete Streptomyces sp.KIB 015
Strain is inoculated into above-mentioned culture medium, and 30 DEG C, shaking table culture 48 hours under the conditions of 200rpm, obtain seed culture fluid.
The configuration of fermentation culture: glucose 800g, beef extract 200g, peptone 200g, yeast extract powder 120g, chlorine are taken
Change sodium 200g, calcium carbonate 120g are dissolved in 40L deionized water, and stirring is allowed to sufficiently dissolve, tune pH to 7.0.Gained 40L is sent out
Ferment culture solution is averagely dispensed into Ermlenmeyer bottles of 160 1000mL baffled, the high-temperature sterilization at 121 DEG C
30min, it is spare.It takes the seed culture fluid 12.5mL prepared in above-mentioned steps to be inoculated into one bottle of fermentation fermentation culture, repeats
Operation completes inoculation operation, then shaking table culture 10 days under the conditions of 30 DEG C, 200rpm.
2. extracting separation
The fermentation liquid that fermentation obtains is obtained into fermented supernatant fluid and mycelia through centrifugal treating (3500rpm, 15min, room temperature)
Body is extracted three times fermented supernatant fluid using isometric ethyl acetate, recycles ethyl acetate in 40 DEG C of reduced pressures, obtain
Medicinal extract part has 9.0g altogether.For the mycelium that fermentation liquid centrifugal treating obtains, using being filtered under diminished pressure after 2L acetone ultrasonication
Filtrate is taken, recycles acetone in 40 DEG C of reduced pressures, gained water phase is extracted three times with 500mL ethyl acetate again, dense in 40 DEG C of decompressions
The total 1.0g in medicinal extract part two is obtained after contracting；Merge two parts medicinal extract and obtains total medicinal extract 10.0g.By total medicinal extract 200-300 mesh silicon
Glue mixes sample, dry column-packing, carries out silica gel column chromatography, with petroleum ether-acetic acid second gradient elution (10:1-0:1), TLC real-time monitoring,
Merge identical flow point, 5 polarity sections are obtained.
Polarity section 3 is through sephadex Sephadex LH-20 and the isolated chemical combination of half preparative high-performance liquid chromatographic of reverse phase
Object 1 (18.0mg), compound 3 (10.0mg) and compound 6 (4.0mg).
Polarity section 4 is through sephadex Sephadex LH-20 and the isolated chemical combination of half preparative high-performance liquid chromatographic of reverse phase
Object 2 (3.0mg), compound 4 (42.0mg) and compound 5 (4.0mg).
Two, Structural Identification:
Compound 1-6's1H and13C NMR data is as shown in Table 1 and Table 2:
1 compound 1-3's of table1H and13C NNR data (Recordedin CD3OD, Jin hz)
aNMR data(δ)were measured at 500MHz for 1H and at 125MHz for 13C.
bNMR data(δ)were measured at 800MHz for 1H and at 200MHz for 13C.
cNMR data(δ)were measured at 600MHz for 1H and at 150MHz for 13C
doverlapped signals.
2 compound 4-6's of table1H and13C NMR data (Recorcded in CD3OD, Jin Hz)a
aNMR data(δ)were measured at 600MHz for 1H and at 150MHz for 13C.
By high resolution mass spectrum to compound 1-6, ultraviolet spectra, infrared spectroscopy, specific rotatory power, electronic circular dichroism,
The data such as nuclear magnetic resonance carry out comprehensive analysis (in conjunction with table 1, table 2 and Fig. 1 to Fig. 6), so that it is determined that the structure of compound 1-6.
Experimental example
Below with reference to cell experiment to 6 pyrroles's sesquiterpenoids provided in an embodiment of the present invention in immunosupress side
The effect in face is evaluated.
One, experimentation:
1. compound 1-6 is to Anti-human-CD3/CD28 induced activation and phytohemagglutin phytolectin induced activation people T
The inhibiting effect of cell Proliferation.
Compound 1-6 is thin to Anti-human-CD3/CD28 induced activation and phytohemagglutin phytolectin induced activation people T
The inhibiting effect of born of the same parents' proliferation is determined by flow cytometry analysis, and 5-carboxyfluorescein diacetate is chosen
The case where succinimide ester (CFSE) is used as marker, handles without the T cell and respective compound of induced activation is made
For negative control (0%), the case where T cell through induced activation is handled without respective compound as positive control (100%),
As a result as shown in Figure 6 and Figure 7.
2. compound 4 is proliferated the Mechanism Study for generating inhibiting effect to T cell.
Human T-cell through dual anti-anti-CD3/anti-CD28 induced activation through various concentration compound 4 (1.25,5,
20 μM) and (50 μM) of drug LY294002 processing, it is incubated for 24 hours, the expression of T cell surface molecular CD25 passes through fluidic cell
Instrument analysis determines, as a result takes in Fig. 8 shown in A and B.Supernatant in aforesaid operations is after collection via enzyme-linked immunosorbent assay
(ELISA) the secretion situation for measuring proleulzin (IL-2), as a result as shown in C in Fig. 8.Meanwhile using 1.25,5 or 20 μM
Compound 4 or (0.1 μM) of drug rapamycin human T-cell of the processing through dual anti-anti-CD3/anti-CD28 induced activation,
The period locating for flow cytometry analysis cell after 72 hours, as a result as shown in D in Fig. 8.
Two, experiment conclusions:
Compound 1-6 to Anti-human-CD3/CD28 induced activation and phytohemagglutin phytolectin
Human T-cell's proliferation of (phytohemagglutin, PHA) induced activation shows different degrees of inhibiting effect, with chemical combination
The inhibitory activity that object 4 is shown is the most significant.
Show that compound 4 can show significantly human T-cell for the Mechanism Study of the immunosuppressive activity of compound 4
Immunosuppressive action, rather than to human T-cell generate cytotoxic effect.When compound 4 shows immunosuppressive action and it is immunized
The secretion of the expression and proleulzin (IL-2) that activate closely bound up T cell surface molecular CD25 is unrelated, it is lived by retardance
The change T cell period generates immunosuppressive action in the G0/G1 phase.
Compound 1-6 has the potentiality for being developed into immunosuppressor as a result,.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of pyrroles's sesquiterpenoids, structural formula is as shown in general formula I:
In formula, C11-R1Selected from by substituted or unsubstituted C4~10It is alkane, substituted or unsubstituted cycloalkane, substituted or unsubstituted
At least one of heterocycloalkane composition group；
R2Selected from OH or H；
It is expressed as singly-bound or double bond.
2. pyrroles's sesquiterpenoids according to claim 1, which is characterized in that R1Selected from by substituted or unsubstituted
C4~10The group of at least one of alkane, substituted or unsubstituted pentamethylene, substituted or unsubstituted tetrahydrofuran composition.
3. pyrroles's sesquiterpenoids according to claim 1, which is characterized in that work as C7-C8-C9-C10Between be list
When key, C8With C11Between form C8-O-C11Key, R1Structure it is as follows:
4. pyrroles's sesquiterpenoids according to claim 1, which is characterized in that work as C7-C8-C9-C10Between only one
A double bond and be located at C8-C9Between when, C11-R1Structure it is as follows:
5. pyrroles's sesquiterpenoids according to claim 1, which is characterized in that work as C7With C8Between be double bond when,
C11-R1Selected from the group being made of following groups:
6. pyrroles's sesquiterpenoids according to claim 1, which is characterized in that it is described in following number 1~6
Any particular compound:
7. a kind of preparation method of pyrroles's sesquiterpenoids as claimed in any one of claims 1 to 6, which is characterized in that its
Include:
015 strain of streptomycete Streptomyces sp.KIB is subjected to fermented and cultured, obtains culture solution；
After the culture solution is extracted with ethyl acetate, total medicinal extract is obtained, total leaching is isolated and purified using chromatography separation method
Cream obtains formula (I) compound；Wherein, the chromatography separation method includes silica gel column chromatography, glucan Sephadex LH-20
Gel filtration chromatography, half preparative high-performance liquid chromatographic of reverse phase.
8. the preparation method of pyrroles's sesquiterpenoids according to claim 7, which is characterized in that the strain into
The condition of row fermented and cultured is: 27-33 DEG C of temperature, incubation time 8-12 days；The liquid training of fermented and cultured is carried out to the strain
Feeding base includes: 15-25 parts of glucose according to parts by weight, and 3-8 parts of beef extract, 3-8 parts of peptone, 3-8 parts of yeast extract powder, chlorine
Change sodium 3-8 parts, 1-5 parts of calcium carbonate.
9. a kind of pyrroles's sesquiterpenoids as claimed in any one of claims 1 to 6 answering in preparation immunosuppressor
With.
10. a kind of pharmaceutical composition, which is characterized in that its active constituent includes such as pyrrole of any of claims 1-6
Cough up sesquiterpenoids and pharmaceutically acceptable auxiliary material.
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| US20060052436A1 (en) * | 2004-08-18 | 2006-03-09 | Venkat Rami Reddy Macherla | Pyrroloterpenes and use of the same as antimicrobial and anticancer agents |
| CN102174083A (en) * | 2011-02-16 | 2011-09-07 | 中国科学院昆明植物研究所 | Compositae cyclopeptide, immunosuppressive medicine using compositae cyclopeptide as active ingredient and preparation method and application of compositae cyclopeptide |
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2019
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|---|---|---|---|---|
| US20060052436A1 (en) * | 2004-08-18 | 2006-03-09 | Venkat Rami Reddy Macherla | Pyrroloterpenes and use of the same as antimicrobial and anticancer agents |
| CN102174083A (en) * | 2011-02-16 | 2011-09-07 | 中国科学院昆明植物研究所 | Compositae cyclopeptide, immunosuppressive medicine using compositae cyclopeptide as active ingredient and preparation method and application of compositae cyclopeptide |
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| DONG-ZE LIU等: "《Structural elucidation and NMR assignments of two new pyrrolosesquiterpenes from Streptomyces sp. Hd7-21》", 《MAGN. RESON. CHEM.》 * |
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