CN106187984A - A kind of mouth xanthones compounds and its preparation method and application - Google Patents
A kind of mouth xanthones compounds and its preparation method and application Download PDFInfo
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- CN106187984A CN106187984A CN201610536316.1A CN201610536316A CN106187984A CN 106187984 A CN106187984 A CN 106187984A CN 201610536316 A CN201610536316 A CN 201610536316A CN 106187984 A CN106187984 A CN 106187984A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—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
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
- C07D311/86—Oxygen atoms, e.g. xanthones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/51—Gentianaceae (Gentian family)
Abstract
The invention discloses the mouth xanthones compounds (1) of a kind of suppression 5 alpha-reductases, described mouth xanthones compounds be from black purple Herba Swertiae bimaculatae (Swertia atroviolaceaIsolated in), its molecular formula is C18H18O5, this Compound nomenclature is: 6 (2 ethoxy) 1,7 dimethoxy 3 methyl mouth diphenylene ketone oxide, English entitled 6 (2 hydroxyethyl) 1,7 dimethoxy 3 methyl xanthone, has a following structural formula:(1) preparation method of described mouth xanthones compounds, is with black purple Herba Swertiae bimaculatae as raw material, obtains through extractum extraction, MCI decolouring, silica gel column chromatography, high pressure liquid chromatography separating step.Described mouth xanthones compounds, through 5 alpha-reductase active testings, has good inhibiting effect to 5 alpha-reductases.The compounds of this invention simple in construction, and there are preferable 5 alpha-reductase inhibitory action, can be as the lead compound preparing 5 alpha reductase inhibitors.
Description
Technical field
The invention belongs to technical field of phytochemistry, be specifically related to a kind of extract, from black purple Herba Swertiae bimaculatae, the mouth obtained first
Xanthones compounds.Meanwhile, the invention still further relates to preparation method and the 5α-reductase inhibitory activity thereof of this compound.
Background technology
Swertia (Swertia) it is a genus under Gentianaceae, about 170 kinds of the whole world, China has more than 80 to plant, mainly
It is distributed in the ground such as Yunnan, Sichuan.In China, this platymiscium is used as medicine with a long history, and medicinal have 35 kinds, has clearing heat secreting bile, dehumidifying solution
The effects such as poison, are usually used in treating the diseases such as acute Jaundice Jaundice, osteomyelitis.The chemical composition of this platymiscium is enriched, and mainly has
The compounds such as mouth diphenylene ketone oxide, flavone, iridoid, triterpene and alkaloid.Black purple Herba Swertiae bimaculatae (Swertia atroviolacea) be Swertia herbaceos perennial, be born in height above sea level 3400～4575 m patana,
In many tors top or rock seam, it it is the peculiar kind in Diqingzangzu area, Yunnan Province.
Mouth diphenylene ketone oxide has another name called dibenzopyrans ketone, and its derivant is widely present in nature, is the important of medicinal plants
One of effective ingredient.Owing to mouth diphenylene ketone oxide analog derivative is to have Fen Xing functional group on three rings of linear array, mostly have rich
Rich biological activity and medical value；Xanthone derivative has physiology and pharmacological activity widely, has antitumor, guarantor
Protect cardiovascular, reduce blood glucose, antioxidation, the pharmacological action such as antibacterial, but a lot of pharmacological mechanism is still in the research and probe stage,
So that its pharmacologically active and the research with configuration relationship thereof receive much attention.The present invention is isolated one from the black purple Herba Swertiae bimaculatae
Planting the mouth xanthones compounds with 5α-reductase inhibitory activity, this compound it is not yet seen relevant report.
Summary of the invention
The first object of the present invention is to provide a kind of new mouth xanthones compounds；Second purpose is to provide described mouth
The preparation method of xanthones compounds；3rd purpose is to provide described mouth xanthones compounds as 5α-reductase inhibitor
Application.
The first object of the present invention is achieved in that described mouth xanthones compounds is complete from dry black purple Herba Swertiae bimaculatae
Isolated in grass, its molecular formula is C18H18O5, it is named: 6-(2-ethoxy)-1,7-dimethoxy-3-methyl-mouth diphenylene ketone oxide,
English entitled 6-(2-hydroxyethyl)-1,7-dimethoxy-3-methyl-xanthone, there is following structural formula:
This compound is light yellow gum thing.
The second object of the present invention is achieved in that the preparation method of the mouth xanthones compounds described in, is with dry
Dry black purple Herba Swertiae bimaculatae herb is raw material, through extractum extraction, MCI decolouring, silica gel column chromatography, high pressure liquid chromatography step, specifically
For:
A, extractum extract: taking dry black purple Herba Swertiae bimaculatae herb is raw material, is pulverized, with extracting 3 ~ 5 under 95% ethanol room temperature
Secondary, each 3 days, united extraction liquid, filtration, concentrating under reduced pressure extracting solution, stand, filter precipitate, be condensed into extractum a；
B, MCI decolour: extractum a MCI post decolours, and with 80%-95% methanol aqueous solution eluting, merge organic facies, and concentrating under reduced pressure becomes
Extractum b；
C, silica gel column chromatography: 80 ~ 100 mesh silica gel dry column-packings of extractum b weight ratio 8 ~ 10 times amount carry out silica gel column chromatography；With
Volume proportion is that the chloroform/acetone solution of 1:0,9:1,8:2,7:3,6:4,1:1 and 0:1 carries out gradient elution, collects gradient and washes
De-liquid, concentration, merge identical part；
D, high pressure liquid chromatography separate: the 7:3 part inverted C18 medium pressure liquid chromatography of step C eluent is isolated and purified, institute
Obtain the eluent that 20 ~ 35 min chromatographic peaks are corresponding, isolated and purified through high pressure liquid chromatography further, obtain described mouth diphenylene ketone oxide class
Compound.
The structure of mouth xanthones compounds prepared by method described above is to identify out by the following method:
The compounds of this invention is light yellow gum thing；High resolution mass spectrum (HRESIMS) provides quasi-molecular ion peakm/z
337.1059 [M+Na]+(value of calculation 337.1052).In conjunction with1H and13 C H NMR spectroscopy provides molecular formula C18H18O5, insatiable hunger
It is 10 with degree.Ultraviolet spectra has absorption maximum at 338,256 and 210 nm, it was demonstrated that there is aromatic ring structure in compound；Red
External spectrum data also confirm that and there are hydroxyl (3420 cm in compound-1), carbonyl (1654 cm-1) and aromatic ring 1606,1529,
1468 cm-1) functional group.Compound1H and13C NMR data (table-1) display compound has 18 carbon and 18 hydrogen letters
Number, including a 1,3,6,7-quaternary mouth diphenylene ketone oxide skeleton [Ind.Crop.Prod., 58, 125 (2014)]
(C-1 ~ C-9, C-4a, C-8a ~ C10a；H-2, H-4, H-5 and H-8), an ethoxy (C-1 ' and C-2 '；H2-1 ' and H2-
2 '), a virtue nuclear substituted methyl (C-3 ' and H3-3 '), 2 methoxyl groups (δ H55.9 q and 56.3 q；3.80 s and
3.83 s).Compound exists H2-1′ (δH2.62) and C-5 (δ C 119.8)、C-6 (δ C 141.3)、C-7 (δ C
158.5), H2-2′ (δH3.64) and C-6 (δ C141.3), and H-5 (δ H7.02) and C-1 ' (δ C 35.2)
HMBC is correlated with (Fig. 3), it can be verified that ethoxy is substituted in the C-6 position of compound.According to H3-3′ (δH2.38) and C-2 (δ C
112.2)、C-3 (δ C 147.2)、C-4 (δ C108.6) HMBC is correlated with, it can be verified that methyl is substituted in the C-3 of compound
Position.Two methoxy substitutions can be by two methoxyl group hydrogen (δ at C-1 and C-7H 3.80 and 3.83) respectively with C-1 (δ C
160.2) and C-7 (δ C158.5) HMBC is relevant to be confirmed.Typical proton signal in compound [δ H 7.08 d
(2.2), 6.87 d (2.2), 7.02 s, 7.43 s] the mouth diphenylene ketone oxide B ring of also supporting the present invention is the 6,7-bis-replacement, C
Ring is 1,3-bis-replacement.So far the structure of the compounds of this invention is determined, Compound nomenclature is: 6-(2-ethoxy)-1,7-
Dimethoxy-3-methyl-mouth diphenylene ketone oxide.
Infrared, the ultraviolet of compound and mass spectrometric data: UV (methanol),λ max (log ε ) 210 (4.06)、256
(3.64), 338 (3.47), IR (pressing potassium bromide troche)ν max 3420、3085、2928、1654、1606、1529、1468、
1412、1360、1273、1208、1158、1064、869 cm-1；1H NMR and13C NMR data (CDCl3, 500 and 125
MH) ,-1 it is shown in Table；ESI-MS (positive ion mode)m/z 337 [M+Na]+;HR-ESI-MS (positive ion mode)m/z [M + Na]+337.1059 (value of calculation 337.1052, C18H18NaO5)。
Table-1. compound1H NMR and13(solvent is C to C NMR data5D5N)
| No. | d C | d H (m, J , Hz) | No. | d C | d H (m, J , Hz) |
| 1 | 160.2 s | 4a | 154.4 s | ||
| 2 | 112.2 d | 7.08 d (2.2) | 8a | 113.9 s | |
| 3 | 147.2 s | 9a | 110.2 s | ||
| 4 | 108.6 d | 6.87 d (2.2) | 10a | 148.2 s | |
| 5 | 119.8 d | 7.02 s | 1′ | 35.2 t | 2.62 t (7.2) |
| 6 | 141.3 s | 2′ | 63.2 t | 3.64 t (7.2) | |
| 7 | 158.5 s | 3′ | 24.2 q | 2.38 s | |
| 8 | 111.5 d | 7.43 s | 1-OMe | 55.9 q | 3.80 s |
| 9 | 176.7 s | 7-OMe | 56.3 q | 3.83 s |
The third object of the present invention is achieved in that described mouth xanthones compounds answering as 5α-reductase inhibitor
With.
The compounds of this invention is separated, by nuclear magnetic resonance, NMR and measuring method of mass spectrum first from black purple Herba Swertiae bimaculatae
It is defined as a mouthful xanthones compounds, and characterizes its concrete structure.This compound is tested through 5α-reductase inhibitory activity, result
Showing, it is 68.4 ± 4.3% to 5α-reductase suppression ratio, shows that this compound has prominent 5α-reductase inhibitory activity.
The compounds of this invention novel structure activity preferably, can have good answering as the guiding compound of 5α-reductase inhibitor
Use prospect.
Accompanying drawing explanation
Fig. 1 is the proton nmr spectra of mouth xanthones compounds of the present invention；
Fig. 2 is the carbon-13 nmr spectra of mouth xanthones compounds of the present invention；
Fig. 3 be mouth xanthones compounds of the present invention main HMBC and1H-1H COSY relevant indicators.
Detailed description of the invention
The present invention is described in further detail with embodiment below in conjunction with the accompanying drawings, but never in any form to the present invention
Being any limitation as, based on present invention teach that any conversion or improvement made, each falling within protection scope of the present invention.
Except as otherwise noted, the percent employed in the present invention is percentage by volume.
Mouth xanthones compounds of the present invention, is isolated from dry black purple Herba Swertiae bimaculatae herb, its molecule
Formula is C18H18O5, there is following structural formula:
This compound is light yellow gum thing, named: 6-(2-ethoxy)-1,7-dimethoxy-3-methyl-mouth diphenylene ketone oxide, English
Literary fame is 6-(2-hydroxyethyl)-1,7-dimethoxy-3-methyl-xanthone.
The preparation method of mouth xanthones compounds of the present invention, is with dry black purple Herba Swertiae bimaculatae herb as raw material,
Through extractum extraction, MCI decolouring, silica gel column chromatography, high pressure liquid chromatography step, particularly as follows:
A, extractum extract: taking dry black purple Herba Swertiae bimaculatae herb is raw material, is pulverized, with extracting 3 ~ 5 under 95% ethanol room temperature
Secondary, each 3 days, united extraction liquid, filtration, concentrating under reduced pressure extracting solution, stand, filter precipitate, be condensed into extractum a；
B, MCI decolour: extractum a MCI post decolours, and with 80%-95% methanol-water eluting, merge organic facies, and concentrating under reduced pressure becomes extractum
b；
C, silica gel column chromatography: 80 ~ 100 mesh silica gel dry column-packings of extractum b weight ratio 8 ~ 10 times amount carry out silica gel column chromatography；With
Volume proportion is that the chloroform/acetone solution of 1:0,9:1,8:2,7:3,6:4,1:1 and 0:1 carries out gradient elution, collects gradient and washes
De-liquid, concentration, merge identical part；
D, high pressure liquid chromatography separate: the 7:3 part inverted C18 medium pressure liquid chromatography of step C eluent is isolated and purified, institute
Obtain the eluent that 20 ~ 35 min chromatographic peaks are corresponding, isolated and purified through high pressure liquid chromatography further, obtain described mouth diphenylene ketone oxide class
Compound.
The extractum b of described step C, before silica gel column chromatography, mixes molten by the chloroform/methanol of weight ratio 1.5～3 times amount
Agent is dissolved, and then weighs the 80～100 mesh silica gel mixed samples of 1 ~ 1.5 times with extractum.
The anti-phase C18 medium pressure liquid chromatography of described D step is isolated and purified be with 21.2 mm × 250 mm, 5μThe C of m18
Chromatographic column is fixing phase, and the acetonitrile with 45% is flowing phase, and flow velocity is 20 mL/min, and UV-detector detection wavelength is 338
Nm, each sample introduction 2 mL, collect the chromatographic peak of 20 ~ 35 min.
Eluent corresponding to 20 ~ 35min chromatographic peak of described D step, before high pressure liquid chromatography is isolated and purified, first takes off
Except solvent again with methanol is dissolved.
The high pressure liquid chromatography of described D step is isolated and purified be with 9.4 mm × 250 mm, 5μThe C of m18Chromatographic column is
Fixing phase, the methanol with 52% is flowing phase, and flow rate of mobile phase is 3 mL/min, and UV-detector detection wavelength is 338 nm, often
Secondary sample introduction 50μL, collects chromatographic peak during 25.2 min, is evaporated after repeatedly adding up.
The application of the present invention is the application in preparing 5α-reductase inhibitor of the described mouth xanthones compounds.
Black purple Herba Swertiae bimaculatae raw material used by the present invention is not by territorial restrictions, and the black purple Herba Swertiae bimaculatae in any source place all can realize
The present invention, to pick up from the black purple Herba Swertiae bimaculatae raw material in enlightening celebrating area, Yunnan Province, the present invention will be further described below.
Unreceipted concrete technology or condition person in embodiment, according to the technology described by the document in this area or condition or
Person is carried out according to product description.Agents useful for same or instrument unreceipted production firm person, be can by purchase obtain normal
Rule product.If the solution in the present invention only gives solute, do not disclose solvent, then those skilled in the art should know molten
Agent is water.In the present invention, pure chloroform refers to 100% chloroform, and pure acetone refers to that 100% acetone, pure methanol refer to 100% methanol.
Embodiment 1
To pick up from the regional black purple Herba Swertiae bimaculatae of Yunnan Province's enlightening celebrating as raw material.Black purple Herba Swertiae bimaculatae herb is sampled 2.5 kg and shines dry powder
Broken, to extract 4 times under 95% ethanol room temperature, extract 3 days, each 3.5L of extracting solution every time, extracting solution merges, and filters, concentrating under reduced pressure
Become extractum, obtain extractum 121g.Extractum MCI post decolours, and elution requirement is methanol/water 90:10, and the extractum after decolouring is with 240 grams
Chloroform/methanol mixed solvent dissolves, and is subsequently adding 120 grams of 100 mesh silica gel and mixes sample.After mixing sample, by 600 grams of dry method of 100 mesh silica gel
Dress post；The chloroform/acetone solution being followed successively by 1:0,9:1,8:2,7:3,6:4,1:1 and 0:1 by volume ratio carries out gradient elution, receives
Collection gradient eluent, concentration, merge identical part, and wherein volume proportion is that 7:3 elution fractions is passed through hydraulic fluid in anti-phase C18
Phase chromatograph, this medium pressure liquid chromatography use 21.2 mm × 250 mm, 5μThe C of m18Chromatographic column, flow rate of mobile phase is 20 mL/
Min, flowing is the acetonitrile of 45% mutually, and UV-detector detection wavelength is 210,230 nm, and each sample introduction 2 mL collects 20 ~ 35
Eluent corresponding to min chromatographic peak, dissolves with methanol after eluent desolvation, and lysate is passed through high pressure liquid chromatography again and enters
Row isolated and purified, this high pressure liquid chromatography use 9.4 mm × 250 mm, 5μThe C of m18Chromatographic column, flow rate of mobile phase is 3
ML/min, flowing is the methanol of 52% mutually, and UV-detector detection wavelength is 338 nm, each sample introduction 50μL, collects chromatographic peak
The eluent that retention time is corresponding when being 25.2 min, is evaporated after repeatedly adding up, obtains described mouth xanthones compounds.
Embodiment 2
To pick up from the regional black purple Herba Swertiae bimaculatae of Yunnan Province's enlightening celebrating as raw material.Black purple Herba Swertiae bimaculatae herb sampling 2.0kg is shone dry grinding,
To extract 3 times under 95% ethanol room temperature, extracting 3 days, each 3.0L of extracting solution, extracting solution merges every time, filters, and concentrating under reduced pressure becomes
Extractum, obtains extractum 105g.Extractum MCI post decolours, and elution requirement is methanol/water 90:10, and the extractum after decolouring is with 200 grams of chlorine
Imitative/methanol mixed solvent dissolves, and is subsequently adding 100 grams of 80 mesh silica gel and mixes sample.After mixing sample, with 500 grams of dry column-packings of 80 mesh silica gel；
The chloroform/acetone solution being followed successively by 1:0,9:1,8:2,7:3,6:4,1:1 and 0:1 by volume ratio carries out gradient elution, collects ladder
Degree eluent, concentration, merge identical part, and wherein volume proportion is that 7:3 elution fractions is passed through hydraulic fluid phase color in anti-phase C18
Spectrum, this medium pressure liquid chromatography use 21.2 mm × 250 mm, 5μThe C of m18Chromatographic column, flow rate of mobile phase is 20 mL/min,
Flowing is the acetonitrile of 45% mutually, and UV-detector detection wavelength is 210,230 nm, and each sample introduction 2 mL collects 20 ~ 35 min colors
Eluent corresponding to spectral peak, dissolves with methanol after eluent desolvation, and lysate is passed through high pressure liquid chromatography again to be carried out point
From purification, this high pressure liquid chromatography use 9.4 mm × 250 mm, 5μThe C of m18Chromatographic column, flow rate of mobile phase is 3 mL/
Min, flowing is the methanol of 52% mutually, and UV-detector detection wavelength is 338 nm, each sample introduction 50μL, collects chromatographic peak and protects
Stay the eluent that the time is corresponding when being 25.2 min, be evaporated after repeatedly adding up, obtain described mouth xanthones compounds.
Embodiment 3
The compound of Example 1 preparation, for light yellow gum thing；
Assay method is: with nuclear magnetic resonance, NMR, identify structure in conjunction with other spectroscopic technique.
High resolution mass spectrum (HRESIMS) provides quasi-molecular ion peakm/z 337.1059 [M+Na]+(value of calculation
337.1052).In conjunction with1H and13 C H NMR spectroscopy provides molecular formula C18H18O5, degree of unsaturation is 10.Ultraviolet spectra 338,
Absorption maximum is had, it was demonstrated that compound exists aromatic ring structure at 256 and 210 nm；Ir data also confirms that in compound
There are hydroxyl ((3420 cm-1)), carbonyl (1654 cm-1) and aromatic ring 1606,1529,1468 cm-1) functional group.Compound1H and13C NMR data (table-1) display compound there are 18 carbon and 18 hydrogen signals, take including a 1,3,6,7-tetra-
The mouth diphenylene ketone oxide skeleton in generation [Ind.Crop.Prod., 58,125 (2014)] (C-1 ~ C-9, C-4a, C-8a ~ C10a；
H-2, H-4, H-5 and H-8), an ethoxy (C-1 ' and C-2 '；H2-1 ' and H2-2 '), a nuclear substituted methyl of virtue
(C-3 ' and H3-3 '), 2 methoxyl groups (δ H55.9 q and 56.3 q；3.80 s and 3.83 are s).Compound exists H2-1′
(δH2.62) and C-5 (δ C 119.8)、C-6 (δ C 141.3)、C-7 (δ C158.5), H2-2′ (δH3.64) and C-
6 (δ C141.3), and H-5 (δ H7.02) and C-1 ' (δ C 35.2) HMBC is correlated with (Fig. 3), it can be verified that ethoxy
It is substituted in the C-6 position of compound.According to H3-3′ (δH2.38) and C-2 (δ C 112.2)、C-3 (δ C 147.2)、C-4
(δ C108.6) HMBC is correlated with, it can be verified that methyl is substituted in the C-3 position of compound.Two methoxy substitutions are at C-1 and C-7
Can be by two methoxyl group hydrogen (δH 3.80 and 3.83) respectively with C-1 (δ C160.2) and C-7 (δ C158.5) HMBC
It is correlated with and is confirmed.The typical proton signal of compound [δ H 7.08 d (2.2)、6.87 d (2.2)、7.02 s、7.43 s]
Also the mouth diphenylene ketone oxide B ring supporting the present invention is the 6, and 7-bis-replacement, C ring is 1,3-bis-replacement.So far the knot of the compounds of this invention
Structure is determined, Compound nomenclature is: 6-(2-ethoxy)-1,7-dimethoxy-3-methyl-mouth diphenylene ketone oxide.
Infrared, the ultraviolet of compound and mass spectrometric data: UV (methanol),λ max (log ε ) 210 (4.06)、256
(3.64), 338 (3.47), IR (pressing potassium bromide troche)ν max 3420、3085、2928、1654、1606、1529、1468、
1412、1360、1273、1208、1158、1064、869 cm-1；1H NMR and13C NMR data (CDCl3, 500 and 125
MH) ,-1 it is shown in Table；ESI-MS (positive ion mode)m/z 337 [M+Na]+;HR-ESI-MS (positive ion mode)m/z [M + Na]+337.1059 (value of calculation 337.1052, C18H18NaO5)。
Table-1. compound1H NMR and13(solvent is C to C NMR data5D5N)
| No. | d C | d H (m, J , Hz) | No. | d C | d H (m, J , Hz) |
| 1 | 160.2 s | 4a | 154.4 s | ||
| 2 | 112.2 d | 7.08 d (2.2) | 8a | 113.9 s | |
| 3 | 147.2 s | 9a | 110.2 s | ||
| 4 | 108.6 d | 6.87 d (2.2) | 10a | 148.2 s | |
| 5 | 119.8 d | 7.02 s | 1′ | 35.2 t | 2.62 t (7.2) |
| 6 | 141.3 s | 2′ | 63.2 t | 3.64 t (7.2) | |
| 7 | 158.5 s | 3′ | 24.2 q | 2.38 s | |
| 8 | 111.5 d | 7.43 s | 1-OMe | 55.9 q | 3.80 s |
| 9 | 176.7 s | 7-OMe | 56.3 q | 3.83 s |
Embodiment 4
In Example 1, the mouth xanthones compounds of preparation carries out 5α-reductase inhibitory activity test, and test case is as follows:
The method that active testing uses dispersive liquid-liquid microextraction-makings to be used in conjunction is tested, and concrete operations are: by 50μG prostatitis
Gland microsomal protein, 500nM testosterone (T), 1mM dithiothreitol, DTT (DTT), 25μL DMSO is dissolved in 40mM sodium phosphate
Buffer solution (pH 6.5) is configured to reactant liquor, and is dissolved to 0.5 ml, adds 250 in reactant liquorμM nicotinamide adenine dinucleotide phosphate
(NADPH) start enzymatic reaction, and cultivate 60 minutes in 37 DEG C of vibration water-baths.500 are added to reactant liquor afterwards in ice bathμL MeCN stops enzymatic reaction.Mouth xanthones compounds, testosterone and the side of dihydrotestosterone dispersive liquid-liquid microextraction of preparation
Formula extracts.Reactant liquor continuously adds 50μL internal standard substance T-d3(175 nM) and DHT-13C3(175 nM) and 50μL tri-
Vinyl chloride, and be transferred in the conical pipe equipped with 3 ml water.Close conical pipe, manually after concussion, be centrifuged 3 points with 5000 × g
Clock, after being centrifuged, will comprise the 30 of the mouth xanthones compounds of preparationμL lower floor material is transferred in new bottle,
The nitrogen stream using gentleness is dried at room temperature for.30 are added after being driedμl MSTFA+NH4I+DTE(500:4:2 vol/wt/
Wt) under domestic microwave (600 w), reaction makes compound carry out silylation reactive for 5 minutes.After having reacted, extract 1μ
L reactant carries out GC/MS analysis.T/ T-d3With DHT/ DHT-13C3Between ratio can be to testosterone with through 5α-reductase
The dihydrotestosterone that reaction generates quantifies, and the amount of the dihydrotestosterone by generating after contrast enzymatic reaction determines tested chemical combination
The 5α-reductase inhibitory activity of thing.
The positive control of the mouth xanthones compounds 5α-reductase inhibitory activity using finasteride to be test preparation,
Finasteride is dissolved in DMSO, and with 40mM buffer solution of sodium phosphate (pH 6.5) is diluted, and extracts 1μM's is dilute
Release liquid and carry out enzymatic reaction.For determining the finasteride IC to 5α-reductase inhibitory activity50Value, uses variable concentrations
Finasteride (0.01～1μM) test, the equal parallel assay of each concentration 3 times.
By above method of testing, determine the 5α-reductase suppression ratio of the mouth xanthones compounds of preparation be 68.4 ±
4.3%, display compound has prominent 5α-reductase inhibitory activity.
Claims (7)
1. a mouth xanthones compounds, it is characterised in that described mouth xanthones compounds is from dry black purple Herba Swertiae bimaculatae herb
Middle isolated, its molecular formula is C18H18O5, named: 6-(2-ethoxy)-1,7-dimethoxy-3-methyl-mouth diphenylene ketone oxide, English
Literary fame is 6-(2-hydroxyethyl)-1,7-dimethoxy-3-methyl-xanthone, has a following structural formula:
。
2. the preparation method of a mouth xanthones compounds according to claim 1, it is characterised in that with dry black purple
Herba Swertiae bimaculatae herb is raw material, through extractum extraction, MCI decolouring, silica gel column chromatography, high pressure liquid chromatography step, particularly as follows:
A, extractum extract: taking dry black purple Herba Swertiae bimaculatae herb is raw material, is pulverized, with extracting 3 ~ 5 under 95% ethanol room temperature
Secondary, each 3 days, united extraction liquid, filtration, concentrating under reduced pressure extracting solution, stand, filter precipitate, be condensed into extractum a；
B, MCI decolour: extractum a MCI post decolours, and with 80 ~ 95% methanol aqueous solution eluting, merge organic facies, and concentrating under reduced pressure becomes leaching
Cream b；
C, silica gel column chromatography: 80 ~ 100 mesh silica gel dry column-packings of extractum b weight ratio 8 ~ 10 times amount carry out silica gel column chromatography；With
Volume proportion is that the chloroform/acetone solution of 1:0,9:1,8:2,7:3,6:4,1:1 and 0:1 carries out gradient elution, collects gradient and washes
De-liquid, concentration, merge identical part；
D, high pressure liquid chromatography separate: the 7:3 part inverted C18 medium pressure liquid chromatography of step C eluent is isolated and purified, institute
Obtain the eluent that 20 ~ 35 min chromatographic peaks are corresponding, isolated and purified through high pressure liquid chromatography further, obtain described mouth diphenylene ketone oxide class
Compound.
The preparation method of the most according to claim 2 mouthful of xanthones compounds, it is characterised in that the extractum b of described step C
Before silica gel column chromatography, dissolve with the chloroform/methanol mixed solvent of weight ratio 1.5～3 times amount, then weigh 1 ~ 1.5 with extractum
80～100 mesh silica gel mixed samples again.
The preparation method of the most according to claim 2 mouthful of xanthones compounds, it is characterised in that described D step anti-phase
C18 medium pressure liquid chromatography is isolated and purified be with 21.2 mm × 250 mm, 5μThe C of m18Chromatographic column is fixing phase, with 45%
Acetonitrile for flowing phase, flow velocity is 20 mL/min, UV-detector detection wavelength be 338 nm, each sample introduction 2 mL, collect 20 ~
The chromatographic peak of 35 min.
The preparation method of the most according to claim 2 mouthful of xanthones compounds, it is characterised in that the 20 of described D step ~
Eluent corresponding to 35min chromatographic peak is before high pressure liquid chromatography is isolated and purified, and first desolvation again with methanol is dissolved.
The preparation method of the most according to claim 2 mouthful of xanthones compounds, it is characterised in that the high pressure liquid of described D step
Phase chromatographic separation and purification be with 9.4 mm × 250 mm, 5μThe C of m18Chromatographic column is fixing phase, and the methanol with 52% is for flowing
Phase, flow rate of mobile phase is 3 mL/min, and UV-detector detection wavelength is 338 nm, each sample introduction 50μL, collects 25.2
Chromatographic peak during min, is evaporated after repeatedly adding up.
7. the application in preparing 5α-reductase inhibitor of the mouth xanthones compounds described in a claim 1.
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| CN107467712A (en) * | 2017-07-28 | 2017-12-15 | 云南中烟工业有限责任公司 | It is a kind of with the tobacco sauce additive of antibacterial activity and its application |
| CN113234084A (en) * | 2021-05-18 | 2021-08-10 | 云南民族大学 | Compound with anti-rotavirus activity in agrimony and thalictrum aquilegifolium and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107467712A (en) * | 2017-07-28 | 2017-12-15 | 云南中烟工业有限责任公司 | It is a kind of with the tobacco sauce additive of antibacterial activity and its application |
| CN107467712B (en) * | 2017-07-28 | 2019-05-21 | 云南中烟工业有限责任公司 | A kind of tobacco sauce additive and its application with antibacterial activity |
| CN113234084A (en) * | 2021-05-18 | 2021-08-10 | 云南民族大学 | Compound with anti-rotavirus activity in agrimony and thalictrum aquilegifolium and preparation method thereof |
| CN113234084B (en) * | 2021-05-18 | 2023-05-05 | 云南民族大学 | Compound with anti-rotavirus activity in Meadowrue of Crane celebration and preparation method thereof |
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