CN106349032A - Bibenzyl compound, preparation method thereof and use thereof in preparation of antitumor drugs - Google Patents

Bibenzyl compound, preparation method thereof and use thereof in preparation of antitumor drugs Download PDF

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Publication number
CN106349032A
CN106349032A CN201610722938.3A CN201610722938A CN106349032A CN 106349032 A CN106349032 A CN 106349032A CN 201610722938 A CN201610722938 A CN 201610722938A CN 106349032 A CN106349032 A CN 106349032A
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compound
pharmaceutically acceptable
solvate
acceptable salt
ethyl acetate
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CN106349032B (en
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彭成
戴鸥
熊亮
仰莲
郭力
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Chengdu University of Traditional Chinese Medicine
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Chengdu University of Traditional Chinese Medicine
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a compound represented by a formula II (shown in the description) or pharmaceutically acceptable salt, crystal forms and solvates thereof. According to the compound, R1 and R2 are respectively independently selected from hydroxyl group or sulfydryl; and R3 and R4 are respectively independently selected from C1-C4 alkyl or halogen-substituted C1-C4 alkyl.

Description

Bibenzyl compound and preparation method thereof and the purposes in preparing antitumor drug
Technical field
The present invention relates to Bibenzyl compound and preparation method thereof and the purposes in preparing antitumor drug.
Background technology
Existing document reports Bibenzyl compound as follows, has suppression passive cutaneous anaphylaxis, PCA (passive Cutaneous anaphylaxis) and suppression rbl-2h3 cell (basophilic leukemia cell) release β-hexosaminidase Drug effect and purposes (see matsuda h et al.antiallergic phenanthrenes and ... planta med 2004；70:847-855):
At present, there are no the research report of compound shown in formula, more there are no chemical combination shown in formula Thing is used for preparing the research report of antitumor drug.
Content of the invention
It is an object of the invention to provide all different new Bibenzyl compound of a kind of structure and medical value: formula institute The compound showing.
The compound shown in formula or its pharmaceutically acceptable salt, crystal formation, solvate that the present invention provides:
Wherein,
r1、r2Separately it is selected from hydroxyl or sulfydryl；
r3、r4Separately it is selected from c1～c4Alkyl or the c of halogen substiuted1～c4Alkyl.
Further, r1、r2It is simultaneously selected from hydroxyl.
Further, r3、r4Separately it is selected from methyl, ethyl, propyl group or isopropyl.
Further, described compound is
Present invention also offers a kind of method of prepare compound c, it comprises the following steps:
I, take Pseudobulbus Bletillae (Rhizoma Bletillae), with ethanol extraction, obtain ethanol extract；
Ii, take ethanol extract, concentrate, obtain fluid extract；
Iii, fluid extract is water-dispersible, use ethyl acetate, n-butanol extraction, combined ethyl acetate part successively, reclaim Solvent, obtains ethyl acetate extract；
Iv, take ethyl acetate extract, using silica gel column chromatography, with petroleum ether-acetone=100:1,50:1,30:1 be successively Eluant carries out gradient elution, obtains eluent fr.16 during petroleum ether-acetone=30:1；
The upper anti-phase polystyrene type resin post of v, fr.16, successively with alcohol-water=10:90,30:70,50:50,70:30, 90:10,100:0 carry out gradient elution for eluant, obtain fr.16-j during alcohol-water=100:0；
Vi, fr.16-j upper sephadex chromatography post, with methylene chloride-methanol=1:1 as eluant, eluting 0.8 successively Times column volume, 2.2 times of column volumes, respectively obtain fr.16-j-1, fr.16-j-2；
Vii, fr.16-j-2 through silica gel column chromatography, with methylene chloride-methanol=1:0 as eluant, 3 cylinders of eluting Long-pending, recycling design, obtain fr.16-j-2a；Fr.16-j-2a passes through and prepares thin layer chromatography, with dichloromethane-acetone=20:1 is Developing solvent, rf=0.65, separate, obtain compound c.
Further,
In step iv, the amount of described ethyl acetate extract is 155～165g, and the condition of gradient elution is as follows:
In step v, the amount of described fr.16 is 15～20g, and the condition of gradient elution is as follows:
Present invention also offers above-mentioned compound or its pharmaceutically acceptable salt, crystal formation, solvate are controlled in preparation Purposes in the medicine for the treatment of and/or prophylaxis of tumours.
Further, described tumor is cancer.
Further, described cancer is pulmonary carcinoma.
Present invention also offers a kind for the treatment of and/or prophylaxis of tumours pharmaceutical composition, it be with above-claimed cpd or its Pharmaceutically acceptable salt, crystal formation, solvate are active component, add the preparation that the adjuvant pharmaceutically commonly used prepares.
The noval chemical compound shown in formula that the present invention provides, has good inhibiting effect to tumor cell, particularly, right Lung carcinoma cell has good inhibiting effect, its ic50Reach 6.37 μ g/ml；Meanwhile, the preparation method letter of the compounds of this invention Just, reaction condition is gentle, is easy to operate and controls, energy consumption is little, yield is high, low cost is especially suitable for industrialization production.
The compound providing in the present invention and derivant can according to iupac (IUPAC) or Cas (chemical abstracts service, columbus, oh) nomenclature is named.
Definition with regard to the use term of the present invention: unless otherwise stated, it is initial that group herein or term provide Definition is applied to this group or the term of entire description；For the term being not specifically defined herein it should according to open Content and context, provide those skilled in the art and can give their implication.
" replacement " refers to that the hydrogen atom in molecule is replaced by other different atoms or molecule.
In hydrocarbon group, the minima of carbon content and maximum are represented by prefix, for example, prefix ca～cbAlkyl table Bright any comprise " a " is to the alkyl of " b " individual carbon atom.Thus, for example, c1～c4Alkyl refers to comprise the alkane of 1～4 carbon atom Base, in other words, c1～c4Alkyl includes methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group.
Term " pharmaceutically acceptable " refers to certain carrier, load, diluent, adjuvant, and/or the salt being formed is usual In chemistry or physically compatible with the other one-tenth split-phases constituting certain pharmaceutical dosage form, and physiologically compatible with by body phase.
Term " salt " and " pharmaceutically useful salt " refer to above-claimed cpd or its stereoisomer, with inorganic and/or organic acid The acid being formed with alkali and/or basic salt, also include amphion salt (inner salt), also include quaternary ammonium salt, such as alkylammonium salt.This A little salt can be compound be finally separating with purification in directly obtain.Can also be by by above-claimed cpd, or it is vertical Body isomer, is obtained by mixing with a number of acid or alkali suitably (such as equivalent).These salt may be in the solution Form precipitation and collected with filter method, or reclaim after the solvent evaporates and obtain, or lyophilization after reaction in aqueous medium It is obtained.Heretofore described salt can be the hydrochlorate of compound, sulfate, citrate, benzene sulfonate, hydrobromate, hydrogen Fluorate, phosphate, acetate, propionate, succinate, oxalates, malate, succinate, fumarate, maleic acid Salt, tartrate or trifluoroacetate.
The method of application of the compounds of this invention or pharmaceutical composition is not particularly limited, and representational method of application includes (but being not limited to): oral, parenteral (intravenouss, intramuscular or subcutaneous) and local are administered.
Solid dosage formss for oral administration include capsule, tablet, pill, powder and granule.In these solid formulation In type, reactive compound is mixed with least one conventional inert excipients (or carrier), such as sodium citrate or dicalcium phosphate, or with Following compositions mix: (a) filler or bulking agent, for example, starch, Lactose, sucrose, glucose, Mannitol and silicic acid；B () bonds Agent, for example, hydroxymethyl cellulose, alginate, gelatin, polyvinyl pyrrolidone, sucrose and arabic gum；(c) wetting agent, example As glycerol；(d) disintegrating agent, for example, agar, Calcium Carbonate, potato starch or tapioca, alginic acid, some composition silicates, And sodium carbonate；(e) retarding solvent, such as paraffin；(f) absorbsion accelerator, for example, quaternary ammonium compound；(g) wetting agent, such as spermaceti Alcohol and glyceryl monostearate；(h) adsorbent, for example, Kaolin；(i) lubricant, for example, Talcum, calcium stearate, Hard Fat Sour magnesium, solid polyethylene glycol, sodium lauryl sulphate, or its mixture.In capsule, tablet and pill, dosage form also can comprise Buffer agent.
Solid dosage formss such as tablet, Sugar Sphere, capsule, pill and granule can using coating and shell material preparation, such as casing and Other materials well known in the art.They can comprise reactive compound in opacifying agent, and, this compositionss or compound Release can discharge in a delayed fashion in certain part in digestive tract.The example of adoptable embedding component is polymeric material And Wax.If necessary, reactive compound also can be with one or more of above-mentioned excipient formation microencapsulation form.
Liquid formulation for oral administration includes pharmaceutically acceptable emulsion, solution, suspension, syrup or tincture. Except active ingredient beyond the region of objective existence, liquid dosage form can comprise the conventional inert diluent adopting in this area, such as water or other solvent, increases Solvent and emulsifying agent, example is known, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3 butylene glycol, dimethyl formyl Amine and oil, particularly Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, maize embryo oil, olive oil, Oleum Ricini and Oleum sesami or the mixture of these materials Deng.
In addition to these inert diluents, compositionss also can comprise auxiliary agent, such as wetting agent, emulsifying agent and suspending agent, sweet taste Agent, correctivess and spice.
Except active ingredient beyond the region of objective existence, suspension can comprise suspending agent, for example, ethoxylation isooctadecane alcohol, polyoxyethylene Mixture of Sorbitol and Isosorbide Dinitrate, Microcrystalline Cellulose, aluminium methoxide and agar or these materials etc..
For parenteral injection compositionss can comprise physiologically acceptable sterile, aqueous or anhydrous solution, dispersion liquid, Suspension or emulsion, and for being again dissolved into the sterilized powder of aseptic Injectable solution or dispersion liquid.Suitable aqueous and Nonaqueous carrier, diluent, solvent or excipient include water, ethanol, polyhydric alcohol and its suitable mixture.
Dosage form for the compounds of this invention of local administration includes ointment, powder, patch, propellant and inhalant. Active component aseptically with physiologically acceptable carrier and any preservative, buffer agent, or if necessary may need Propellant be mixed together.
Pharmaceutically acceptable adjuvant of the present invention, refers to the material being included in dosage form in addition to the active ingredient (s.
Pharmaceutically acceptable complementary composition of the present invention, it has certain physiologically active, but the addition of this composition Leading position in treatment of diseases for the aforementioned pharmaceutical compositions will not be changed, and only play auxiliary effect, these auxiliary Effect is only the utilization to this composition known activity, is the usual adjuvant treatment modality of field of medicaments.If will be above-mentioned complementary Composition is used cooperatively with pharmaceutical composition of the present invention, still falls within the scope of protection of the invention.
Obviously, the above according to the present invention, according to ordinary technical knowledge and the customary means of this area, without departing from Under the premise of the present invention above-mentioned basic fundamental thought, modification, replacement or the change of other various ways can also be made.
The specific embodiment of form by the following examples, remakes further specifically to the above of the present invention Bright.But this scope being interpreted as the above-mentioned theme of the present invention should not be only limitted to Examples below.All based on the above of the present invention The technology realized belongs to the scope of the present invention.
Brief description
Fig. 1 is the hr-esi-ms spectrum of the compounds of this invention c.
Fig. 2 is the compounds of this invention c's1H nmr composes.
Fig. 3 is the compounds of this invention c's13C nmr composes.
Specific embodiment
Used in the specific embodiment of the invention, raw material, equipment are known product, are obtained by buying commercially available prod.
1. medical material
Bletilla striata medicinal materials are purchased from Neijiang City in Sichuan Province in August, 2012, are accredited as white through Chengdu University of Traditional Chinese Medicine professor Li Min And the dry tuber of bletilla striata (thunb.) rchb.f..
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, gf254 and h (chemistry is pure), are purchased from Qingdao Haiyang silica-gel desiccant factory；
Mci gel chp 20p, 75～150 μm, be anti-phase polystyrene type resin, is purchased from Mitsubishi chemical company；
Sephadex lh-20 polydextran gel, is purchased from amersham company of Sweden；
Thin layer prepared by gf254 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, ethyl acetate, n-butyl alcohol, acetone, methanol, are purchased from Chengdu Ke Long chemical reagent factory.
3. experimental apparatus
Cometro 6000 high performance liquid chromatograph (U.S. cometro)；
Waters synapt g2hdms high-resolution flight time mass spectrum (U.S. waters)；
Nuclear magnetic resonance analyser: bruker-600 nuclear magnetic resonance analyser；Temperature of the measurement: 297k；Using solvent peak-to-peak signal as reference；
Vector 22ft-ir infrared spectrometer (Switzerland bruker)；
Shimadzu uv-260 spectrophotometry instrument (Japanese shimadzu)；
Bp211d 100,000/electronic balance (Switzerland sartorius)；
R-210 rotary evaporator (Switzerland buchi)；
Dzg-6050 type vacuum drying oven (the gloomy letter in Shanghai).
Embodiment 1, the extraction of compound c and Structural Identification
(1) extraction of medical material:
The Bletilla striata medicinal materials coarse powder (3kg) being dried, with 95% alcohol reflux 3 times (30l × 3), each 2h；
(2) the isolating and purifying of composition:
1., ethanol extract (90l) through concentrating under reduced pressure dry semisolid flow extractum 510g；
2., semisolid flow extractum (500g) is used water (5l) to disperse, use ethyl acetate (20l), n-butyl alcohol (20l) extraction successively Take, combined ethyl acetate part, decompression and solvent recovery, obtain ethyl acetate extract 160g；
3., ethyl acetate extract (160g) is carried out separate using silica gel column chromatography, petroleum ether: acetone carries out gradient and washes De-, eluent detects through thin layer chromatography, obtains petroleum ether: eluent fr.16 during acetone=30:1；
The condition of gradient elution is as follows:
4., fr.16 component (18g) processes through mci and carries out gradient elution with the ethanol water of 10%-100%v/v, and ties Close thin layer chromatography to be detected, respectively obtain 10 component fr.16-a～fr.16-j；
The condition of gradient elution is as follows:
5., fr.16-j component (3.0g) is through gel lh-20 chromatographic column, with methylene chloride-methanol=1:1 as eluant, Carry out eluting, fr.16-j-1, fr.16-j-2, fr.16-j-3 are respectively 0.8 times of column volume of eluting, 2.2 times of column volumes, 3 times of posts The component collected successively during volume, wherein fr.16-j-2 group are divided into the concentration position of bibenzyl derivative；
6., fr.16-j-2 component (1.8g) is through silica gel column chromatography, respectively with methylene chloride-methanol 1:0,200:1, 100:1,50:1 carry out eluting, 3 column volumes of each ratio eluent, decompression and solvent recovery, collect 1:0 eluting position Fr.16-j-2a, with prepare thin layer chromatography (developing solvent as dichloromethane-acetone=20:1, rf=0.65) separate and obtain compound c；
In Pseudobulbus Bletillae (Rhizoma Bletillae) during the colour developing of Bibenzyl compound thin layer chromatography, spray, with 10% sulphuric acid ethanol test solution, develops the color at 105 DEG C The many displaing yellows of 3min, Chinese red, to blush speckle, can be used for the trace detection of bibenzyl；
Compound c molecular formula c23h24o4, high resolution mass spectrum data: hr-esi-ms m/z 363.1605 [m-h]- (c23h23o4Value of calculation be 363.1596), degree of unsaturation be 12；
Compound c proton nmr spectra (1H-nmr) and carbon-13 nmr spectra (13C-nmr) by bruker-av-600 core Magnetic resonance device measures, and concrete data is shown in Table 1；
Table 1, compound c1H nmr (600mhz) and13c nmr(150mhz)in cd3cocd3Data
Determined by above-mentioned data, for 3 '-hydroxyl -4- to hydroxyl benzyl -3,5- dimethoxy bibenzyl, its structure is such as compound c Under:
Below by way of test example, illustrate beneficial effects of the present invention.
Test example 1 antitumor is tested
(1) experiment material:
1. cell
Lung carcinoma cell a549 derives from atcc company of the U.S..
2. experimental apparatus
Hwcl-1 temperature constant magnetic stirring bathes (Zhengzhou Greatwall Scientific Industrial ＆ Trading Co., Ltd.)；
Bp211d 100,000/electronic balance (Switzerland sartorius)；
Dzg-6050 type vacuum drying oven (the gloomy letter in Shanghai)；
Microplate reader (thermo 3001, thermo fisher scientific company)；
Electronic balance (esj120-4 type, Longteng Electronic Weighing Instrument Co., Ltd., Shenyang)；
Super-clean bench (mcv-b161f (t), Japanese sanyo company)；
Microscope (primo vert, axiocam erc 5s, zeiss company)；
co2Incubator (hh.cp-t, Shanghai Qi Xin scientific instrument company limited).
(2) experimental technique:
1. cell inoculation
Digest the cell of exponential phase with 0.25% pancreatin.It is made into slender with the cell culture medium culture containing 10%fbs Born of the same parents' suspension.Counted using cell counting count board, by a549 tumor cell inoculation in good condition in 96 orifice plates, make cell density be 4 ×103Individual/ml, every hole adds cell suspension 100 μ l, is placed in 37 DEG C, 5%co2Culture 24h in incubator.
2. drug treating
Each sample, from the beginning of 20 μ g/ml, with culture medium gradient dilution sample, 2 times of dilutions, arranges 5 drug level, often Individual concentration does multiple holes test.With concentration be 20,10,5,2.5,1.25 μ g/ml every hole dosing 100 μ l, each concentration set 3 multiple Hole, is repeated 3 times.Negative control group is the culture medium solution containing appropriate dmso, and blank control group is not celliferous culture medium And solvent.96 orifice plates are put back to incubator, 37 DEG C of effect 72h.
3. colour developing and ic50Calculating
After 72h effect finishes, under the conditions of lucifuge, every hole adds mtt solution (5g/l) 20 μ l, after continuing to incubate culture 4h, abandons Fall supernatant, every hole adds 150 μ l dmso, is placed in and shakes 10min at a slow speed on shaking table, after so that first a ceremonial jade-ladle, used in libation is fully dissolved, uses microplate reader Od value at measurement 570nm wavelength.
Using improvement karber's method ic50=log-1[xm-i (∑ p-0.5)] is calculated, the Cmax of wherein xm: design Logarithm value；I: the logarithm value of each concentration multiple proportions concentration；σ p: each group growth inhibition ratio sum；0.5: empirical.By weight Multiple three tests, are calculated 3 ic50Value (reservation two-decimal), averages；Result of the test is shown in Table 2.
Table 2, the cytotoxic activity ic to a549 tumor cell for the Bibenzyl compound c of the present invention50
no. ic50(μg/ml)
Compound c 6.37
The above results show, Bibenzyl compound of the present invention has good inhibiting effect to tumor cell, can be used in Prepare antitumor drug.
In sum, the noval chemical compound shown in formula that the present invention provides, has good inhibiting effect to tumor cell, Particularly, to lung carcinoma cell, there is good inhibiting effect, its ic50Reach 6.37 μ g/ml；Meanwhile, the system of the compounds of this invention Preparation Method is easy, and reaction condition is gentle, is easy to operate and controls, energy consumption is little, yield is high, low cost is especially suitable for industry metaplasia Produce.

Claims (10)

1. the compound shown in formula or its pharmaceutically acceptable salt, crystal formation, solvate:
Wherein,
r1、r2Separately it is selected from hydroxyl or sulfydryl；
r3、r4Separately it is selected from c1～c4Alkyl or the c of halogen substiuted1～c4Alkyl.
2. compound according to claim 1 or its pharmaceutically acceptable salt, crystal formation, solvate it is characterised in that: r1、r2It is simultaneously selected from hydroxyl.
3. compound according to claim 1 or its pharmaceutically acceptable salt, crystal formation, solvate it is characterised in that: r3、r4Separately it is selected from methyl, ethyl, propyl group or isopropyl.
4. the compound according to Claims 2 or 3 or its pharmaceutically acceptable salt, crystal formation, solvate, its feature exists In: described compound is
5. a kind of method of prepare compound c it is characterised in that: it comprises the following steps:
I, take Pseudobulbus Bletillae (Rhizoma Bletillae), with ethanol extraction, obtain ethanol extract；
Ii, take ethanol extract, concentrate, obtain fluid extract；
Iii, fluid extract is water-dispersible, use ethyl acetate, n-butanol extraction successively, combined ethyl acetate part, recycling design, Obtain ethyl acetate extract；
Iv, take ethyl acetate extract, using silica gel column chromatography, successively with petroleum ether-acetone=100:1,50:1,30:1 as eluting Agent carries out gradient elution, obtains eluent fr.16 during petroleum ether-acetone=30:1；
The upper anti-phase polystyrene type resin post of v, fr.16, successively with alcohol-water=10:90,30:70,50:50,70:30,90: 10th, 100:0 carries out gradient elution for eluant, obtains fr.16-j during alcohol-water=100:0；
Vi, fr.16-j upper sephadex chromatography post, with methylene chloride-methanol=1:1 as eluant, 0.8 times of post of eluting successively Volume, 2.2 times of column volumes, respectively obtain fr.16-j-1, fr.16-j-2；
Vii, fr.16-j-2 through silica gel column chromatography, with methylene chloride-methanol=1:0 as eluant, 3 column volumes of eluting, return Receive solvent, obtain fr.16-j-2a；Fr.16-j-2a passes through and prepares thin layer chromatography, with dichloromethane-acetone=20:1 for launching Agent, rf=0.65, separate, obtain compound c.
6. according to claim 5 prepare compound b method it is characterised in that:
In step iv, the amount of described ethyl acetate extract is 155～165g, and the condition of gradient elution is as follows:
In step v, the amount of described fr.16 is 15～20g, and the condition of gradient elution is as follows:
7. the compound described in Claims 1 to 4 any one or its pharmaceutically acceptable salt, crystal formation, solvate are in system Purposes in the medicine of standby treatment and/or prophylaxis of tumours.
8. purposes according to claim 7 it is characterised in that: described tumor be cancer.
9. purposes according to claim 8 it is characterised in that: described cancer be pulmonary carcinoma.
10. a kind for the treatment of and/or prophylaxis of tumours pharmaceutical composition it is characterised in that: it is any one with Claims 1 to 4 The described compound of item or its pharmaceutically acceptable salt, crystal formation, solvate are active component, add the adjuvant pharmaceutically commonly used The preparation preparing.
CN201610722938.3A 2016-08-24 2016-08-24 Bibenzyl compound and preparation method thereof and purposes in the preparation of antitumor drugs Expired - Fee Related CN106349032B (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105001064A (en) * 2015-07-10 2015-10-28 浙江中医药大学 Bletilla striata fibrous root blestriarene A and preparation method and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105001064A (en) * 2015-07-10 2015-10-28 浙江中医药大学 Bletilla striata fibrous root blestriarene A and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
仰莲 等: "白及的化学成分及生物活性研究进展", 《中药与临床》 *
韩广轩 等: "中药白及中一新的联苄化合物", 《药学学报》 *

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