CN111018689A - Patchouli alcohol type sesquiterpene compound and application thereof - Google Patents
Patchouli alcohol type sesquiterpene compound and application thereof Download PDFInfo
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- CN111018689A CN111018689A CN201911217163.4A CN201911217163A CN111018689A CN 111018689 A CN111018689 A CN 111018689A CN 201911217163 A CN201911217163 A CN 201911217163A CN 111018689 A CN111018689 A CN 111018689A
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- patchouli alcohol
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- tamiflu
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- GGHMUJBZYLPWFD-UHFFFAOYSA-N patchoulialcohol Chemical compound C1CC2(C)C3(O)CCC(C)C2CC1C3(C)C GGHMUJBZYLPWFD-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229930004725 sesquiterpene Natural products 0.000 title claims abstract description 18
- GGHMUJBZYLPWFD-MYYUVRNCSA-N Patchouli alcohol Natural products O[C@@]12C(C)(C)[C@H]3C[C@H]([C@H](C)CC1)[C@]2(C)CC3 GGHMUJBZYLPWFD-MYYUVRNCSA-N 0.000 title claims abstract description 14
- -1 sesquiterpene compound Chemical class 0.000 title claims abstract description 14
- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical compound OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 claims abstract description 20
- 229940061367 tamiflu Drugs 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 18
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 241000606265 Valeriana jatamansi Species 0.000 claims description 10
- 241000222666 Boerhavia diffusa Species 0.000 claims description 5
- 235000011751 Pogostemon cablin Nutrition 0.000 claims description 5
- 229940079593 drug Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 238000010898 silica gel chromatography Methods 0.000 abstract description 6
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- 239000007791 liquid phase Substances 0.000 abstract 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
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- 150000001875 compounds Chemical class 0.000 description 8
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- 239000003153 chemical reaction reagent Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
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- 208000004232 Enteritis Diseases 0.000 description 3
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- 241000792902 Valerianaceae Species 0.000 description 3
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical class C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 3
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- RAPAFGOPSFDECW-UHFFFAOYSA-N (-)-(1R,3R,6S,7S,8S,10R)-3-acetoxy-2,2,6,8-tetramethyltricyclo[5.3.1.03,8]undecan-10-one Natural products C1C2C(C)CCC3(O)C2(C)CC(OC(C)=O)C1C3(C)C RAPAFGOPSFDECW-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
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- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
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- 241000282465 Canis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
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- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
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- 101001039853 Sonchus yellow net virus Matrix protein Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 229940124393 anti-influenza virus drug Drugs 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
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- 206010064097 avian influenza Diseases 0.000 description 1
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- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
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- 238000007796 conventional method Methods 0.000 description 1
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- 208000001848 dysentery Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
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- 206010022437 insomnia Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
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- 210000003127 knee Anatomy 0.000 description 1
- GIKLTQKNOXNBNY-OWOJBTEDSA-N lewisite Chemical compound Cl\C=C\[As](Cl)Cl GIKLTQKNOXNBNY-OWOJBTEDSA-N 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
- 150000005692 lignans Chemical class 0.000 description 1
- 235000009408 lignans Nutrition 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229960002194 oseltamivir phosphate Drugs 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229960000888 rimantadine Drugs 0.000 description 1
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- 230000002048 spasmolytic effect Effects 0.000 description 1
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- 230000002936 tranquilizing effect Effects 0.000 description 1
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- XLZVKKAUANEKGL-UHFFFAOYSA-N valeriananoid A Natural products C1C2C(C)CCC3(O)C2(C)CC(=O)C1C3(C)C XLZVKKAUANEKGL-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
- C07C49/487—Saturated compounds containing a keto group being part of a ring containing hydroxy groups
- C07C49/507—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic
- C07C49/513—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/16—Acetic acid esters of dihydroxylic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
Abstract
The invention discloses patchouli alcohol type sesquiterpene compounds and application thereof, wherein two patchouli alcohol type sesquiterpene compounds are obtained by soaking extraction, silica gel column chromatography rough separation, silica gel column chromatography fine separation and liquid phase purification, and the two patchouli alcohol type sesquiterpene compounds have the activity of resisting Tamiflu-resistant H1N1 influenza virus and can be applied to the preparation of lead drugs for treating Tamiflu-resistant H1N1 influenza virus infection.
Description
Technical Field
The invention belongs to the technical field of plant medicinal components and resistance to Tamiflu-resistant influenza viruses, and particularly relates to two patchouli alcohol type sesquiterpene compounds and application thereof.
Background
The large-scale prevalence of Influenza A Virus (IAV) can cause extremely high morbidity and mortality. The major influenza in the 3 th 20 th century (i.e., spanish influenza (H1N 1) in 1918, asian influenza (H2N 2) in 1957 and hong kong influenza (H3N 2) in 1968), H1N1 in 2009, and highly pathogenic avian influenza types H5N1 in 2010 and H7N9 in 2013, which cause death in over ten thousand people worldwide, are all caused by influenza a virus. The influenza virus has the obvious characteristic of high mutation rate of gene replication, so that the current antiviral drugs taking replication as targets are inactivated easily, thereby generating drug resistance and being difficult to generate effective vaccines. To date, there are two major classes of FDA-approved anti-influenza drugs. The first, the adamantanes (amantadine and rimantadine), mainly destroy the activity of the ion channel of the influenza M2 protein. However, the american centers for disease prevention and control have found, on spot, that 100% of H3N2 strain in 2008-09 and H1N1 strain in 2009 pandemic have drug resistance to adamantane drugs, and thus such drugs are no longer used clinically. The second group, tamiflu (oseltamivir phosphate) and lewisite, mainly inhibit the neuraminidase activity of influenza viruses. However, duffy, as a first-line drug against influenza virus, showed resistance to 99.6% of seasonal influenza virus (H1N 1) in 2008-09. Therefore, the development of novel anti-influenza virus drugs is imminent.
China is rich in species, and Chinese medicaments have a long history. Therefore, the extraction and separation technology is beneficial to obtaining the lead compound for resisting the Tamiflu-resistant influenza virus from the traditional Chinese medicine. Root of Aranea incense (Valeriana jatamansiJones is Valerianaceae (Valerianaceae) Valeriana (Valerianaceae) (Jones)Valeriana) The plant has effects of tranquilizing, hypnotizing, anticonvulsive, spasmolytic, dispelling pathogenic wind and relieving pain, and can be used for treating abdominal pain, dyspepsia, diarrhea, dysentery, rheumatalgia, soreness of waist and knees, and insomnia. Phytochemistry research finds that the valeriana jatamansi contain iridoid and volatile oil components mainly, and sesquiterpene and lignan components secondarily. The related research shows that the valeriana jatamansi jones can treat rotavirus enteritis, rotavirus diarrhea, infantile non-rotavirus enteritis and canine parvovirus enteritis. Therefore, the valeriana jatamansi jones play an important role in resisting viruses. However, the basic research on the antiviral action of valeriana jatamansi jones is now performedThe research is less.
Disclosure of Invention
The invention provides two patchouli alcohol type sesquiterpenoids and application thereof in a medicament for resisting Tamiflu-resistant influenza viruses.
The two patchouli alcohol type sesquiterpenoids provided by the invention are active ingredients separated from traditional Chinese medicine valeriana jatamansi, and the names of the compounds 1 and 2 are valeriananoid A and valeriananoid C respectively, and the compounds have the following structures:
the preparation method of the two patchouli alcohol type sesquiterpene compounds has the advantages of simple process and low cost, and specifically comprises the following steps:
(1) taking 25kg of dried valeriana jatamansi jones and rhizome, crushing, soaking and extracting for three times (37L multiplied by 3) at room temperature by using an ethanol aqueous solution with the volume fraction of 95%, soaking for 24 h each time, combining three extracting solutions, distilling under reduced pressure to recover an organic solvent, suspending with water, and filtering to remove fat-soluble precipitate; sequentially extracting the filtrate with petroleum ether, ethyl acetate and n-butanol to obtain a petroleum ether extract, an ethyl acetate extract and an n-butanol extract respectively;
(2) mixing the ethyl acetate extract, performing 100-200-mesh silica gel column chromatography, performing gradient elution by using petroleum ether/acetone in a volume ratio of 100:1, 80:1, 50:1, 20:1, 10:1, 1:1 and 0:1 in sequence, detecting by using thin layer chromatography, and combining the obtained same fractions to obtain 7 fractions Fr 1-Fr 7;
(3) subjecting fraction Fr2 to 200-mesh 300-mesh silica gel column gradient elution with petroleum ether/acetone at volume ratio of 20:1, 15:1, 10:1, 5:1, 1:1, 0:1, dividing into 4 parts Fr2.1-Fr2.4, subjecting Fr2.1 to silica gel column chromatography, gradient elution with chloroform/acetone (1: 0, 100:1, 80:1, 50:1, 20:1, 10:1, 1:1, 0:1, v/v), dividing into two parts Fr2.1.1 and Fr2.1.2; fr2.1.1 is separated and purified by silica gel column, the elution system is chloroform/acetone (1: 0, 100:1, 80:1, 50:1, 20:1, 10:1, 1:1, 0:1, v/v) and is divided into 2 parts, Fr2.1.1.1 and Fr 2.1.1.2; fr2.1.1.2 is eluted by a gel column (chloroform/methanol 1:1, v/v), and then is separated and purified by preparative TLC (petroleum ether/acetone 9:1, v/v) to obtain a compound 2;
(4) fr3 is subjected to gradient elution by a 200-mesh 300-mesh silica gel column by petroleum ether/ethyl acetate with the volume ratio of 20:1, 15:1, 10:1, 5:1, 1:1 and 0:1, and is divided into 4 parts Fr3.1-Fr3.4; fr3.3 is gradient eluted with silica gel in petroleum ether/ethyl acetate in the volume ratio of 40:1, 20:1, 10:1, 5:1 and 1:1 and divided into two parts Fr3.3.1 and Fr 3.3.2; fr3.3.2 using reversed phase MCI column, methanol water system, ethanol volume fraction of 60%, 80%, 90%, 100%, divided into 4 parts, Fr3.3.2.1 by gel (petroleum ether/chloroform/methanol 5:5:1) separation and purification, and HPLC semi-preparation to obtain compound 1.
The invention also provides application of two patchouli alcohol type sesquiterpene compounds in preparation of a medicine for resisting Tamiflu-resistant influenza viruses, the invention utilizes an in-vitro Tamiflu-resistant influenza virus experiment, adopts an influenza A H1N1 (A/puerto Rico/8/1934) virus strain, and the experiment result shows that the two patchouli alcohol type sesquiterpene compounds 1 and 2 have strong inhibition effect on the A/puerto Rico/8/1934 virus strain and EC50Respectively 0.35 +/-0.11 and 0.083 +/-0.017 microgram/mL, so that the two patchouli alcohol type sesquiterpene compounds can be proved to have the activity of resisting the tamiflu-resistant H1N1 influenza virus, can be used as lead compounds for treating the infection of the tamiflu-resistant H1N1 influenza virus, and have potential application value.
The two patchouli alcohol type sesquiterpenes compounds are from valeriana jatamansi jones roots and rhizomes, have wide sources, are simple and easy to extract, and can be widely popularized.
Drawings
Process for preparation of compound 1 of FIG. 11H-NMR spectrum;
FIG. 2 preparation of Compound 113C-NMR spectrum;
FIG. 3 preparation of Compound 21H-NMR spectrum;
FIG. 4 preparation of Compound 213C-NMR spectrum.
Detailed Description
The present invention is further illustrated in detail by the following figures and examples, but the scope of the present invention is not limited thereto, and the reagents in the examples are all conventional commercially available reagents or reagents prepared by a conventional method, unless otherwise specified.
Preparation of the Compound of example 1
The extraction and separation (preparation) of patchouli sesquiterpenes comprises the following specific steps:
(1) taking 25kg of dried valeriana jatamansi jones and rhizome, crushing, soaking and extracting for three times (37L multiplied by 3) at room temperature by using an ethanol aqueous solution with the volume fraction of 95%, soaking for 24 h each time, combining three extracting solutions, distilling under reduced pressure to recover an organic solvent, suspending with water, and filtering to remove fat-soluble precipitate; sequentially extracting the filtrate with petroleum ether, ethyl acetate and n-butanol to obtain a petroleum ether extract, an ethyl acetate extract and an n-butanol extract respectively;
(2) mixing the ethyl acetate extract, performing 100-200-mesh silica gel column chromatography, sequentially performing gradient elution by using petroleum ether/acetone in a volume ratio of 100:1, 80:1, 50:1, 20:1, 10:1, 1:1 and 0:1, detecting by using a thin layer chromatography, and combining the obtained same fractions to obtain 7 fractions (Fr 1-Fr 7);
(3) subjecting fraction Fr2 to 200-mesh 300-mesh silica gel column, gradient eluting with petroleum ether/acetone at volume ratio of 20:1, 15:1, 10:1, 5:1, 1:1, and 0:1, and dividing into 4 parts Fr2.1-Fr2.4; fr2.1 by silica gel column chromatography, eluting with chloroform/acetone (1: 0, 100:1, 80:1, 50:1, 20:1, 10:1, 1:1, 0:1, v/v) gradient, and dividing into two parts, Fr 2.1.1-Fr 2.1.2; fr2.1.1 is separated and purified by silica gel column, the elution system is chloroform/acetone (1: 0, 100:1, 80:1, 50:1, 20:1, 10:1, 1:1, 0:1, v/v) and is divided into 2 parts, Fr 2.1.1-Fr 2.1.1.2; fr2.1.1.2 is eluted by a gel column (chloroform/methanol 1:1, v/v), and then is separated and purified by preparative TLC (petroleum ether/acetone 9:1, v/v) to obtain a compound 2, namely the valeriananoid C;
(4) fr3 is subjected to gradient elution by a 200-mesh 300-mesh silica gel column with petroleum ether/ethyl acetate in the volume ratio of 20:1, 15:1, 10:1, 5:1, 1:1 and 0:1, and is divided into 4 parts, Fr3.1-Fr 3.4; fr3.3 Petroleum Ether/Ether in silica gel at volume ratio of 40:1, 20:1, 10:1, 5:1, 1:1Gradient eluting with ethyl acetate to obtain two fractions Fr3.3.1-Fr3.3.2; fr3.3.2 uses reversed phase MCI column, methanol water system, ethanol volume fraction of 60%, 80%, 90%, 100%, 4 parts, Fr3.3.2.1 is separated and purified by gel (petroleum ether/chloroform/methanol 5:5:1), HPLC (volume fraction of 40% methanol water, 3mL/min,t R =12.35min) semi-preparation to give compound 1, valiianoid a.
Example 2 structural analysis of the Compound
By physicochemical constants and modern spectroscopic methods (NMR), combined with literature-relevant data, their structures were determined as follows:
structural identification data for compounds 1 and 2 are shown in figures 1, 2, 3, 4 and table 1 below:
TABLE 1 Hydrogen and carbon Spectroscopy data for Compound 1 and Compound 2
Compound 1:1H-NMR：600 MHz；13C-NMR：150 MHz。
compound 2:1H-NMR：500 MHz；13C-NMR：125 MHz。
EXAMPLE 3 study of anti-influenza Virus Activity of Compounds
(1) Cytotoxicity experiments:
1) Madin-Darby canine kidney cells (MDCK) were seeded in 96-well plates at 5000/well in 5% CO at 37 ℃2Culturing for 24 hours under the condition; the cells were divided into the following 2 groups:
① cell control group containing MDCK cells only;
② drug group, compound 1, compound 2 and Tamiflu (Tamiflu) were added to MDCK cells, respectively;
2) wherein the compound 1, the compound 2 and the Tamiflu (Tamiflu) prepared in the example 1 are added into MDCK cells in a drug group, and the concentration gradient is 0.020, 0.078, 0.313, 1.25, 5 and 20 mu g/mL;
3) continuing at 37 ℃ with 5% CO2Culturing for 48h under the condition, and then adding Promega CellTiter-Glo reagents into each hole;
4) detecting absorbance values using a Promega Victor III plate reader;
5) the cytotoxicity of the compound against MDCK was calculated by the following formula:
cytotoxicity (%) = (cell control-drug group)/(cell control) × 100;
CalcuSyn software (Biosoft, Cambridge, UK) was used to calculate CC50(drug concentration at 50% cell death), the specific results are shown in Table 2.
(2) Anti-influenza virus activity:
1) MDCK cells were seeded in 96-well plates at 5000/well in 5% CO at 37 ℃2Cells were cultured under conditions for 24 hours and divided into the following 3 groups:
① cell control group containing MDCK cells only;
② virus control group, MDCK cells were supplemented with virus only;
③ drug and virus group (Tamiflu as positive control), Compound 1, Compound 2, Tamiflu and the same virus as the virus control group prepared in example 1 were added to MDCK cells, respectively;
2) wherein the concentration gradient of the compound 1, the compound 2 and the Tamiflu (Tamiflu) respectively treated cells prepared in example 1 is 0.020, 0.078, 0.313, 1.25, 5, 20 μ g/mL, and the virus is influenza a H1N1 virus with a multiplicity of infection (MOI) of 1 (a/Puerto Rico/8/1934);
3) continuing at 37 ℃ with 5% CO2Culturing for 48h under the condition, and then adding Promega CellTiter-Glo reagents into each hole;
4) detecting absorbance values using a Promega Victor III plate reader;
5) the protective effect of the compounds on influenza virus infected cells was calculated by the following formula:
cell protection rate (%) = (drug and virus group-virus control group)/(cell control group-virus control group) × 100;
calculation of EC Using Calcusyn software50(concentration required to protect 50% of MDCK cells from killing by influenza virus), specific results are shown in Table 2.
The inhibitory activities of the patchouli alcohol- type sesquiterpenes 1 and 2 prepared according to example 1 against influenza A H1N1 virus are shown in Table 2. from the results in Table 2, it can be seen that the two patchouli alcohol-type sesquiterpenes have very good inhibitory activity against A/Puerto Rico/8/1934 virus strain.
TABLE 2 inhibitory Effect of Compound 1 and Compound 2 on influenza A H1N1 Virus (A/Puerto Rico/8/1934)
Claims (3)
1. Patchouli alcohol type sesquiterpene compounds with the structural formula shown in formulas 1 and 2:
2. the patchouli alcohol-type sesquiterpene compound of claim 1, which is isolated from the traditional Chinese medicine valeriana jatamansi jones.
3. The use of the patchouli alcohol-type sesquiterpene compound of claim 1 in the preparation of a medicament for treating Tamiflu-resistant influenza virus.
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Non-Patent Citations (6)
| Title |
|---|
| A. SRIKRISHNA等: "Enantioselective Total Synthesis of Valeriananoids A-C", 《ORGANIC LETTERS》 * |
| DONG SHENG MING等: "The Structures of Three Novel Sesquiterpenoids from Valeriana Jatamansi Jones", 《TETRAHEDRON LETTERS》 * |
| HE-HAI JIANG等: "Cav2.2 and Cav3.1 calcium channel inhibitors from Valeriana jatamansi Jones", 《RSC ADV.》 * |
| MASAKAZU FUKUSHIMA等: "Total synthesis of valeriananoids A, B, and C via autocatalytic diastereoselective domino Michael reaction", 《TETRAHEDRON》 * |
| 叶和平等: "Michael加成反应及其在天然产物全合成中的应用", 《广州化工》 * |
| 苏丽花: "两种药用植物的化学成分和生物活性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
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