CN104151373B - Lignan glycoside compounds and preparation method thereof - Google Patents

Lignan glycoside compounds and preparation method thereof Download PDF

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CN104151373B
CN104151373B CN201410198470.3A CN201410198470A CN104151373B CN 104151373 B CN104151373 B CN 104151373B CN 201410198470 A CN201410198470 A CN 201410198470A CN 104151373 B CN104151373 B CN 104151373B
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ethanol
water
methanol
hydroxyl
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CN104151373A (en
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郭力
熊亮
张廷模
李小红
郭平
郭一平
韩瑜
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SICHUAN WAN'AN DENDROBIUM INDUSTRY DEVELOPMENT Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C07H1/08—Separation; Purification from natural products
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings

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Abstract

The invention provides compounds with a structure as shown in a formula I in the specification, wherein R1 and R2 represent glycosyl, R3 is H, hydroxyl or methoxyl, R4 represents hydroxyl or methoxyl, and R5 represents H, hydroxyl or methoxyl. The invention also provides a preparation method and a use of the compounds. The compounds, namely 8,4'-O-neolignan glycoside compounds obtained from dendrobe, have inhibiting effect on glutamic acid-induced PC12 cellular neural toxicity, have a certain neural cell protecting effect and can be used for treating neurodegenerative diseases.

Description

A kind of lignanoid glycosides compound and preparation method thereof
Technical field
The present invention relates to a kind of 8,4 '-oxygen neolignan glycoside compound and preparation method thereof.
Background technology
Dendrobium is a maximum genus in orchid family, including about 1100 kinds of plants, is distributed mainly on Tropical Asia and peace Foreign island.About 63 kinds of Dendrobium Sws of China, are made for 39 kinds of medicinal Dendrobium Sw.From vertically seeing 100～3000 meters of height above sea level Height be all distributed.Harvest in the fall more than medicinal dendrobium, cutting is dried, or using fresh herb.Sweet in the mouth, cold nature.Energy replenishing YIN and removing heat, benefit Stomach promotes the production of body fluid.For consumption of body fluid by heat, low grade fever excessive thirst, the few tongue of red tongue；Deficiency of stomach-Yin, thirsty and dry pharynx, vomiting is eaten less, vague epigastralgia, tongue The few tongue of light；Deficiency of kidney yin, blurring of vision.
Herba Dendrobii is a common kind in Dendrobium, is distributed widely in southern china each province, early-stage Study shows it Containing various active metabolite, including bibenzyl, luxuriant and rich with fragrance class, Fluorenone, Phenylpropanoid Glycosides, flavone and Coumarinses etc..In Chinese medicine In application, Herba Dendrobii is commonly used for antipyretic, improving eyesight, immunomodulating, antioxidation, antitumor and slow down aging, has widely Physiologically active.Intensification Herba Dendrobii being recognized with people and the progress of modern science and technology, Herba Dendrobii active component and active component Research carry out rapidly, but the research for Herba Dendrobii lignan glycosides is also little, and the activity about neurocyte protection is ground Study carefully and also extremely lack.
Content of the invention
It is an object of the invention to provide the new lignan glycosides compound of the class that comes from Herba Dendrobii.The present invention's is another Purpose is to provide the preparation method of such compound and purposes.
The invention provides the compound as shown in formula or its pharmaceutically acceptable salt, its structure is as follows:
Wherein, r1、r2For glycosyl, r3For h, hydroxyl or methoxyl group；r4For hydroxyl or methoxyl group；r5For h, hydroxyl or methoxy Base.
Further, described structural formula of compound is as follows:
Wherein, described r1、r2It is respectively selected from glucosyl group, xylosyl or rhamanopyranosyl.
Further, described r1、r2It is respectively selected from glucosyl group.
Further, described r3For methoxyl group.
Further, described r4For hydroxyl.
Further, described r5For methoxyl group.
Further, described compound is 4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane -7 ' - Alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides.
Preferably, described compound be ()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen New wood fat alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides.
Present invention also offers above-mentioned ()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen is new Wooden fat alkane -7 '-alkene -7,9,9 '-triol 7, the preparation method of 9 '-bis--o- beta -d-glucose- glycosides, it includes following operational approach:
(1) take stem of Dendrobium, pulverize, plus 95%v/v ethanol extraction, united extraction liquid, after recycling design, obtain ethanol leaching Cream；
(2) ethanol extract is water-dispersible, use ethyl acetate, n-butanol extraction successively, merge n-butanol fraction, reclaim molten After agent, obtain n-butyl alcohol extractum；With nonpolarity macroporous adsorptive resins chromatographic column, n-butyl alcohol extractum is carried out again separating, successively with water, 10% V/v ethanol, 30%v/v ethanol elution, take 30%v/v ethanol elution part, upper anti-phase c18 liquid chromatograph, 5%-90%v/v Aqueous methanol gradient eluting, collects 40%-50% methanol-water elution fraction；
(3) the 40%-50%v/v methanol-water elution fraction in operation (2) is again through hydroxypropyl polydextran gel post separation, first Alcohol-water=1:1 eluting, thin layer is followed the trail of, and collects the eluent containing target compound, recycling design, residue inverted liquid again Phase preparative hplc separates, and purification obtains final product.
By pulverizing medicinal materials in the present invention, it is conventional extraction pre-treating method in field of phytochemistry, medical material can be increased Specific surface area, improves extraction efficiency, if but with raw material extracting directly although extraction efficiency is relatively low, but equally can carry Obtain corresponding chemical composition, can be similarly adapted to the present invention.
Heretofore described ethanol extraction, including various extracting modes such as backflow, warm macerating, ultrasonic, normal pressure or decompression extractions, As long as with ethanol as solvent, being aided with conventional sense means, all can reach same or analogous extraction effect.
When going up macroporous resin and gel column eluting in above-mentioned steps, all can be by thin layer method for tracing commonly used in the art To monitor or suitably to adjust elution action.
Further, described nonpolar macroporous adsorption resin is d101.
Further, in step (3), the chromatographic condition of described reverse phase liquid preparative hplc is as follows:
Chromatographic column is c18Semi-preparative column；Flow velocity is 1.5ml/min；Detection wavelength is 210nm；Mobile phase is 37%v/v first Alcohol-water solution.
Wherein, stem of Dendrobium of the present invention derives from Herba Dendrobii dendrobium aurantiacum The stem of var.denneanum.
Present invention also offers above-claimed cpd or its pharmaceutically acceptable salt protect the medicine of neurocyte in preparation In purposes.
Further, described medicine is prevention or/and the medicine for the treatment of neurodegenerative diseases.
Unless otherwise stated, the original definition of group herein or term offer is applied to this group of entire description Or term.For the term being not specifically defined herein it should according to the disclosure of invention and context, provide this area Technical staff can give their implication.
All stereoisomers of the compounds of this invention, and racemic mixture is also all the part of the present invention.Separately Outward, all of geometric isomer or position isomer are also included.
Term " pharmaceutically acceptable salt " refers to the compounds of this invention or its stereoisomer, and inorganic and/or organic Acid and/or basic salt that bronsted lowry acids and bases bronsted lowry is formed, also include amphion salt (inner salt), also include quaternary ammonium salt, such as alkylammonium salt. These salt can be compound be finally separating with purification in directly obtain.Can also be by by the compounds of this invention, or Its stereoisomer, is obtained by mixing with a number of acid or alkali suitably (such as equivalent).These salt may be molten Form precipitation in liquid and collected with filter method, or reclaim after the solvent evaporates and obtain, or freeze after reaction in aqueous medium It is dried and be obtained.For example, the compounds of this invention and hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid, phosphoric acid, citric acid, malic acid, first are included Acid, maleic acid, acetic acid, malonic acid, pamoic acid, 1,5- naphthalenedisulfonic acid, cyclohexylsulfamic, salicylic acid, adipic acid, penta 2 The shapes such as acid, vanillic acid, oxaloacetic acid, ascorbic acid, lactic acid, fumaric acid, succinic acid, tartaric acid, methanesulfonic acid or p-methyl benzenesulfonic acid The salt becoming, or, the salt containing sodium, potassium, magnesium, zinc or ferrum etc. that the compounds of this invention is formed with alkali, but be not limited thereto.
In addition to compound of the present invention and its pharmaceutically acceptable salt, the related pharmacy of described compound precursor medicine Purposes also should be included within the scope of the present invention, and wherein, described prodrug refers to formula i compound of the present invention The conversion through enzyme or non-enzymatic in vivo obtaining after modifying for chemical structure discharges active component and plays the chemical combination of drug effect Thing.
In one embodiment of the present invention, present invention comprises isotope-labeled formula i compound, described isotope mark Remember that compound refers to same with listed compound phase herein, but one or more of atom replaced by another atom, The atomic mass of this atom or mass number are different from common atomic mass in nature or mass number.Can be with introduction-type iization Isotope in compound includes hydrogen, carbon, nitrogen, oxygen, sulfur, i.e. 2h, 3h, 13c, 14c, 15n, 17o, 18o, 35s.Containing above-mentioned same position The compound of formula i of plain and/or other atom isotope and its stereoisomer, and this compound, stereoisomer can Medicinal salt should be included within the scope of the invention.
In some embodiments, one or more compound of the present invention can be used in conjunction with one another.Also may be selected will The compound of the present invention is used in combination with any other active agent, for preparing the medicine of regulating cell function or treatment disease Thing or pharmaceutical composition.If using one group of compound, can by these compounds simultaneously, respectively or in an orderly manner to tested Object is administered.
The present invention obtain from Herba Dendrobii 8,4 '-oxygen neolignan glycoside compound, the pc12 cell that glutamic acid is led to Neurotoxicity has inhibitory action, has certain neurocyte protection to act on, and can be used for treating neurodegenerative diseases.
Brief description
The ir figure of Fig. 1 compound
The hr-esi-ms figure of Fig. 2 compound
Fig. 3 compound1H-nmr schemes
Fig. 4 compound13C-nmr schemes
The hsqc figure of Fig. 5 compound
The hmbc figure of Fig. 6 compound
The cd figure of Fig. 7 compound
Specific embodiment
Embodiment 1 ()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane -7 ' - The extracting and developing purification of alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides and Structural Identification
(1) experiment material:
1. medical material
Herba Dendrobii picks up from Sichuan Chengdu double fluid, is provided by Sichuan Wan An Herba Dendrobii company, through Chengdu University of Traditional Chinese Medicine's TCD identification Teaching and research room professor Li Min is accredited as the stem of orchid Herba Dendrobii dendrobium aurantiacum var.denneanum.
2. reagent and filler
Column chromatography silica gel, 200～300 mesh (SILVER REAGENT), it is purchased from Qingdao Haiyang silica-gel desiccant factory；
Tlc silica gel g, gf254With h (chemistry is pure), it is purchased from Qingdao Haiyang silica-gel desiccant factory；
Sephadex lh-20 polydextran gel, is purchased from amersham company of Sweden；
gf254Thin layer prepared by silica gel, is purchased from Yantai Jiang You silica gel development corporation, Ltd.；
Chromatograph methanol, 4l/ bottle, it is purchased from fisher company of the U.S.；
The analytical reagent such as petroleum ether, chloroform, dichloromethane, ethyl acetate, n-butyl alcohol, methanol, are purchased from Chengdu section dragonization Work chemical reagent work.
3. experimental apparatus
Agilent1200series high performance liquid chromatograph (U.S. agilent)；
waters synapt g2Hdms high-resolution flight time mass spectrum (U.S. waters)；
Inova-500 nuclear magnetic resonance analyser；
Vector22ft-ir infrared spectrometer (Switzerland bruker)；
Shimadzu uv-260 spectrophotometry instrument (Japanese shimadzu)；
Perkin-elmer341 polariscopy instrument (U.S. perkinelmer)；
Bp211d 100,000/electronic balance (Switzerland sartorius)；
R-210 rotary evaporator (Switzerland buchi)；
Dzg-6050 type vacuum drying oven (the gloomy letter in Shanghai).
(2) extraction of medical material: weigh dry stem of Dendrobium 10kg, pulverize, plus 95% ethanol (30l) flows back 3 times, every time 3 Hour, merge ethanol extract, decompression and solvent recovery, obtain ethanol extract 530g；
(3) the isolating and purifying of composition:
1. ethanol extract is disperseed with water (2.5l), use ethyl acetate (3 × 2.5l), n-butyl alcohol (3 × 2.5l) extraction successively Take, merge n-butanol fraction, after recycling design, obtain n-butyl alcohol extractum 110g；
2. n-butyl alcohol extractum is carried out separate using d-101 type macroporous adsorptive resins (1.5kg), successively with water, 10% Ethanol, 30% ethanol, 50% ethanol and 95% ethanol elution, each elution volume is 4l, obtains corresponding five parts；
3. take 30% ethanol elution part 48g, upper anti-phase c18 medium pressure liquid chromatography, 5%-90% methanol aqueous solution ladder Degree eluting, is monitored with thin layer during collecting 40%-50% methanol-water elution fraction, eluting；
4. further by upper for 40%-50% methanol-water elution fraction (6.5g) hydroxypropyl sephadex column (sephadex Lh-20,20 150 μm, 150g) separate, methanol-water (1:1) eluting, thin layer is followed the trail of, and collects the eluting containing target compound Liquid, recycling design, obtain crude compound；
5. the inverted liquid phantom preparing chromatogram of crude compound separates, chromatographic column model: ultimate type semi-preparative column (250 × 10mm), filler is c18(5μm)；Flow velocity is 1.5ml/min；Detection wavelength is 210nm；Mobile phase is 37% methanol-water Solution, collect chromatograph main peak, decompression and solvent recovery, obtain final product compound ()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-four Methoxyl group -8,4 '-oxygen new wood fat alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides (6.5mg).
(4) Structural Identification of composition: colorless gum, infrared spectrum shows oh (3374cm-1) and aromatic ring (1588 Hes 1502cm-1) absworption peak.High resolution mass spectrum hr-esi-ms provides quasi-molecular ion peak ([m+na]+, m/z783.2681), table The molecular formula of bright compound is c34h48o19, degree of unsaturation is 11.Compound1H-nmr shows two symmetrical 1,3,4,5- tetra- Substituted benzene ring [δ 6.77 (h-2 ', 6 '), 6.72 (h-2,6)] and two fragrant methoxyl group signals (δ 3.78,3.73)；Meanwhile, hydrogen Spectrum two alkene Hydrogen Proton signals [δ 6.59 (d, j=16.0hz, h-7 '), 6.35 (dt, j=16.0,6.0hz, h-8 ')] of display, Dd, j=13.0,6.0hz, h-9 ' a), methylene signals [4.43 (4.20 (dd, j=13.0,6.0hz, the h-9 ' of one company's oxygen B)], show to contain a trans-aryl propenyl fragment in molecule.Additionally, hydrogen spectrum shows the methine of two ortho position couplings Signal [δ 5.11 (d, j=3.5hz, h-7), 4.27 (h-8)] and company's Oxymethylene signal [δ 3.59 (h-9a), 3.17 (h- 9b)], illustrate to contain an aryl phenylpropyl alcohol triol fragment in molecule.By two anomeric proton signals [δ 4.34 (d, j=7.5hz, H-1 ' '), 4.22 (1h, d, j=8.0hz, h-1 " ')] and multiple even Oxymethylenes of δ 3.00-3.70 scope and even oxygen methine Signal, shows to exist two β-glucosyl groups in molecule.In compound13In c nmr and dept, also show above corresponding Carbon signal.Data above illustrate the planar structure of compound be 4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat Alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides.This inference has obtained the confirmation of 2d-nmr further, In hmbc spectrum, h-1 ' ' is related to c-4, h-1 " ' related to c-9, h-2/6 is related to c-1, c-3/5, c-4 and c-7, h-8 and c- 4 ' is related, and h-2 '/6 ' and c-1 ', c-3 '/5 ', c-4 ' and c-7 ' are related, h-7 ' and c-1 ', c-2 '/6 ', c-8 ' and c-9 ' phase Close.
In order to determine the absolute configuration of compound, carry out the enzyme digestion reaction of compound, obtain a monosaccharide and aglycon Compound, further measure monosaccharide specific optical rotation beDetermine that this glucose is d- glucose.According to this lignan glycosides Coupling constant (the j of middle h-7 and h-87,8=3.5hz), may infer that phenylpropyl alcohol triol fragment is 7,8- Soviet Union formula configuration.In addition this wood The cd spectrum of fat element glycosides and its aglycon compound is born in 235nm (δ ε -0.18) and 239nm (δ ε -0.22) display respectively Cotton effect, shows that phenylpropyl alcohol triol fragment is 7s, 8r configuration.Therefore, the accurate molecular structure of compound be ()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- β - D- glucoside.
The invention provides new 8,4 ' obtaining from Herba Dendrobii-oxygen neolignan glycoside [()-(7s, 8r, 7 ' e) -4- Hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose-s Glycosides].Their detection data is as follows:
(1) optical rotation: perkin-elmer341 polariscope measures.
(c=0.20, meoh)
(2) infrared spectrum (ir): vector22ft-ir infrared analysis instrument, kbr tabletting measures.
irkbrνmax: 3374,2920,1588,1502,1462,1420,1331,1226,1124,1071,1023,8 35, 706,615cm-1
(3) high resolution mass spectrum (hr-esi-ms): waters synapt g2Hdms instrument measures.
hresi-ms:m/z783.2681[m+na]+(calcd for c34h48o19Na, 783.2687), molecular formula determines For c34h48o19；
(4) proton nmr spectra (1H-nmr): inova-500spectrometer measures, data is shown in Table 1.
(5) carbon-13 nmr spectra (13C-nmr): inova-500spectrometer measures, data is shown in Table 1.
Table 1. compound1h nmr(500mhz)、13C nmr (125mhz) nuclear magnetic data (measures solvent: dmso-d6；δ: ppm；J:hz)
(6) two dimensional NMR heteronuclear single quantum correlation (hsqc): inova-500spectrometer mensure, will divide In son1H core be joined directly together13C core is associated.
(7) two dimensional NMR heteronuclear multiple-bond Correlated Spectroscopy (hmbc): inova-500spectrometer measure it is determined that The link position of group in compound molecule, confirms compound structure.Hmbc relevant information is shown below (arrow head part).
Illustrate beneficial effects of the present invention below by way of test example.
The neurocyte protection determination of activity of test example 1 compound
The pc12 cell (imictron cell) of exponential phase, discards original fluid, with 5 × 103/ pipe is inoculated in and contains 5% hyclone, 5% horse serum, penicillin (100iu/ml), streptomycin (100 μ g/ml) and l- L-Glutamine (2 μm) In 96 orifice plates of dmem culture medium, in 37 DEG C of co2In incubator cultivate 24 hours, be subsequently adding final concentration of 10 μm, 1 μm and 0.1 μm monomeric compound [()-(7s, 8r, 7 ' e) -4- hydroxyl -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane - 7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose- glycosides], and add glutamic acid to 20 μm in the medium, cultivate 24 Hour, as sample sets.In glutamic acid model group, the pc12 cell of exponential phase, discard original fluid, with containing 20 μm of paddy ammonia The dmem complete medium of acid is cultivated, in blank control group, with the dmem culture medium of 5% hyclone and 5% horse serum Carry out cultivating and all cultivate 24 hours.
Each group adds mtt (final concentration 0.5mg/ml) to be further cultured for 4 hours in every hole after cultivating 24 hours.Remove supernatant, often Hole adds 150 μ l dmso to put concussion 5 minutes on micro oscillator, measures the light at 570nm in biorad550 type microplate reader Density value.Cell viability to be evaluated with relative protection ratio.
Experimental result shows, this compound under the concentration of 10 μm, 1 μm and 0.1 μm, pc12 cell that glutamic acid is caused Damage and there is certain protective effect, relative protection ratio is respectively 48.1 ± 2.5%, 25.7 ± 2.2% and 10.9 ± 1.9%, There is drug effect-dose-dependence, show this 8,4 '-oxygen neolignan glycoside has certain protective role to neurocyte, can use Prevention or treatment in neurodegenerative diseases.
The present invention obtain from Herba Dendrobii 8,4 '-oxygen neolignan glycoside compound, the pc12 cell that glutamic acid is led to Neurotoxicity has inhibitory action, has certain neurocyte protection to act on, and can be used for treating neurodegenerative diseases.

Claims (5)

1. compound or its pharmaceutically acceptable salt it is characterised in that: described compound is ()-(7s, 8r, 7 ' e) -4- hydroxyl Base -3,3 ', 5,5 '-tetramethoxy -8,4 '-oxygen new wood fat alkane -7 '-alkene -7,9,9 '-triol 7,9 '-bis--o- beta -d-glucose-s Glycosides.
2. () described in claim 1-(7s, 8r, 7 ' e)-4- hydroxyl-3,3 ', 5,5 '-tetramethoxy-8,4 '-oxygen new wood fat alkane- 7 '-alkene -7,9,9 '-triol 7, the preparation method of 9 '-bis--o- beta -d-glucose- glycosides it is characterised in that: it includes the side of operation as follows Method:
(1) take stem of Dendrobium, pulverize, plus 95%v/v ethanol extraction, united extraction liquid, after recycling design, obtain ethanol extract；
(2) ethanol extract is water-dispersible, use ethyl acetate, n-butanol extraction successively, merge n-butanol fraction, recycling design Afterwards, obtain n-butyl alcohol extractum；With nonpolarity macroporous adsorptive resins chromatographic column, n-butyl alcohol extractum is carried out again separating, use water, 10%v/v successively Ethanol, 30%v/v ethanol elution, take 30%v/v ethanol elution part, upper anti-phase c18 liquid chromatograph, 5%-90%v/v first Alcohol-water solution gradient elution, collects 40%-50%v/v methanol-water elution fraction；
(3) by the 40%-50%v/v methanol-water elution fraction in step (2) through hydroxypropyl polydextran gel post separation, methanol- Water=1:1 eluting, thin layer is followed the trail of, and collects the eluent containing target compound, recycling design, residue inverted liquid phase system again Standby chromatographic isolation, purification obtains final product；
In step (3), the chromatographic condition of described reverse phase liquid preparative hplc is as follows:
Chromatographic column is c18Semi-preparative column；Flow velocity is 1.5ml/min；Detection wavelength is 210nm；Mobile phase is 37%v/v methanol-water Solution.
3. preparation method according to claim 2 it is characterised in that: described nonpolar macroporous adsorption resin be d101.
4. the compound described in claim 1 or its pharmaceutically acceptable salt use in the medicine of preparation protection neurocyte On the way.
5. purposes according to claim 4 it is characterised in that: described medicine be prevention or/and treatment nervus retrogression disease The medicine of disease.
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