CN107383006A - The novel C separated in the Dulong rhizome of Chinese monkshood19Diterpene alkaloid preparation method and its usage - Google Patents

The novel C separated in the Dulong rhizome of Chinese monkshood19Diterpene alkaloid preparation method and its usage Download PDF

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Publication number
CN107383006A
CN107383006A CN201710801073.4A CN201710801073A CN107383006A CN 107383006 A CN107383006 A CN 107383006A CN 201710801073 A CN201710801073 A CN 201710801073A CN 107383006 A CN107383006 A CN 107383006A
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China
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dulong
rhizome
alkaloid
diterpene alkaloid
novel
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CN201710801073.4A
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尹田鹏
陈阳
蔡乐
胡晓芳
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Zunyi Medical University
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Zunyi Medical University
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Priority to CN201710801073.4A priority Critical patent/CN107383006A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems

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

Abstract

The invention discloses from a kind of novel C in the Ranunculaceae aconitum plant Dulong rhizome of Chinese monkshood19The preparation method and its usage of diterpene alkaloid, using the root of the Dulong rhizome of Chinese monkshood as raw material, separated using sour water percolation, solvent extraction, silica gel column chromatography and method of spectroscopy and identify a kind of new C19Diterpene alkaloid taronenine A, extracorporeal anti-inflammatory experiment shows that the compound has the function that the mouse macrophage RAW 264.7 for significantly inhibiting lipopolysaccharide mediate discharges inflammatory factor interleukin 6, is laid a good foundation to develop the anti-inflammatory drug of novelty from such plant.

Description

The novel C separated in the Dulong rhizome of Chinese monkshood19- diterpene alkaloid preparation method and its usage
Technical field
The present invention relates to field of phytochemistry, and in particular to the novel C separated in the root of the Dulong rhizome of Chinese monkshood19- diterpene alkaloid Preparation method and its usage.
Background technology
Aconitum (Aconitum) is Ranunculaceae (Ranunculaceae) 1 year or herbaceos perennial, is important The traditional Chinese medicine medicinal herbs resource plant, such as famous Chinese medicine monkshood, monkshood, radix aconiti agrestis, Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani), Korean aconite roof all originate from this platymiscium.This category Plant has analgesia, wind-damp dispelling and the effect such as antipyretic more.Diterpene alkaloid is the feature active ingredient of this platymiscium, anti-inflammatory, Analgesia, anti-arrhythmia etc. effect are notable.Develop at present and had lappaconitine, 3- for clinical medicinal diterpene alkaloid Acetylaconitine ycorynoline, bulleyaconitine A and Guan-fubase A etc., wherein bulleyaconitine A also can be used for treatment rheumathritis, scapulohumeral periarthritis, bone The inflammation such as arthritis.Therefore the medicine with antiinflammatory action is very likely excavated out from aconitum plant.
The Dulong rhizome of Chinese monkshood (Aconitum taronense Fletcher et Lauener) is China endemic species, originates in China Northwestern Yunnan Province Drung nationality river basin.Its medicinal root tuber wind-damp dispelling of local resident and analgesia, it is evident in efficacy.It yet there are no Dulong crow The chemical composition of head and the report studied in terms of pharmacological action, therefore the research for carrying out anti-inflammatory chemical composition to the Dulong rhizome of Chinese monkshood has weight Big meaning.
The content of the invention
It is an object of the present invention to provide a kind of C of new structure19- type diterpene alkaloid taronenine A and its system Preparation Method and as the application in the precursor or lead compound of anti-inflammatory drug.
A kind of novel C separated in the Dulong rhizome of Chinese monkshood19- diterpene alkaloid taronenine A, structural formula are：
A kind of new diterpene alkaloid preparation method separated in the root of the Dulong rhizome of Chinese monkshood, using following steps：
Step 1：Dulong rhizome of Chinese monkshood Aconitum taronense Fletcher et Lauener dried root 6.0kg are taken, Crush；
Step 2：With 0.5% hydrochloric acid 50L diacolations, react to percolate inanimate object alkali, then alkalized with 10% ammoniacal liquor to pH For 9, extracted with isometric ethyl acetate, extraction three times, combined ethyl acetate, is concentrated under reduced pressure and drains to obtain total alkaloid Medicinal extract 41.5g；
Step 3：Total alkali medicinal extract is through silica gel column chromatography 100-200 mesh gradient elutions VChloroform:VMethanol, 100:1→1:1, TLC inspection Survey merging and obtain nine part FrA-FrI, wherein FrD is 9.0g through silica gel column chromatography 300-400 mesh gradient elutions VPetroleum ether:VAcetone:V TwoEthamine, 100:5:1→100:20:1 isolated target compound 171mg, and identified by 1D/2D NMR and HR-ESIMS Its structure is：
It is using the beneficial effect of above-mentioned technical proposal：
Extracorporeal anti-inflammatory experiment shows that new diterpene alkaloid provided by the present invention can significantly inhibit lipopolysaccharide mediate Inflammatory factor interleukin-6 (the EC that mouse macrophage RAW 264.7 discharges5047.01 ± 0.12 μM of value), show the compound Act on extracorporeal anti-inflammatory, laid a good foundation to develop the anti-inflammatory drug of novelty from such plant.
Brief description of the drawings
Fig. 1 is target compound taronenine A in the present invention1H-NMR spectrum.
Fig. 2 is target compound taronenine A in the present invention13C-NMR spectrograms.
Fig. 3 is target compound taronenine A in the present invention1H-1H COSY spectrograms.
Fig. 4 is the NOESY spectrograms of target compound taronenine A in the present invention.
Fig. 5 is the hsqc spectrum figure of target compound taronenine A in the present invention.
Fig. 6 is the HMBC spectrograms of target compound taronenine A in the present invention.
Embodiment
A kind of novel C separated in the Dulong rhizome of Chinese monkshood19- diterpene alkaloid taronenine A, structural formula are：
A kind of new diterpene alkaloid preparation method in the root of the Dulong rhizome of Chinese monkshood, using following steps：
Step 1：Dulong rhizome of Chinese monkshood Aconitumtaronense Fletcher et Lauener dried root 6.0kg are taken, Crush；
Step 2：With 0.5% hydrochloric acid 50L diacolations, react to percolate inanimate object alkali, then alkalized with 10% ammoniacal liquor to pH For 9, extracted with isometric ethyl acetate, extraction three times, combined ethyl acetate, is concentrated under reduced pressure and drains to obtain total alkaloid Medicinal extract 41.5g；
Step 3：Total alkali medicinal extract is through silica gel column chromatography 100-200 mesh gradient elutions VChloroform:VMethanol, 100:1→1:1, TLC inspection Survey merging and obtain nine part FrA-FrI, wherein FrD is 9.0g through silica gel column chromatography 300-400 mesh gradient elutions VPetroleum ether:VAcetone:V TwoEthamine, 100:5:1→100:20:1 isolated target compound 171mg, and identified by 1D/2D NMR and HR-ESIMS Its structure is：
The C of new structure provided by the present invention19- diterpene alkaloid taronenine A are white powder, bismuth potassium iodide Reacting positive；Molecular formula is C34H47NO10(HR-ESI-MS m/z:630.3274[M+H]+,calcd.630.3278)； m.p.98-99℃； (c 1.0,CHCl3)；IR(KBr,cm-1):νmax 3435,2930,2352,1715, 1608,1453,1255,1103,769；Nuclear magnetic data is as shown in table 1,
The compound of table 11H NMR (400MHz) and13C NMR (100MHz) data (CDCl3)
2D NMR technologies test gained two-dimensional correlation HMBC and1H-1H COSY are such as：
Anti-inflammatory activity is tested：Take the logarithm growth period the cells of RAW 264.7 with 0.25% Trypsin Induced, with containing The DMEM culture mediums of 10% hyclone are made 1 × 107/ mL single cell suspensions, 96 hole cell culture are inoculated in per the μ L of hole 100 Plate, 5%CO237 DEG C of incubation 24h in incubator.The cells of RAW 264.7 are stimulated to establish inflammation mould with 10 μ g/mL lipopolysaccharides (LPS) Type, experiment are divided into six groups：Blank control group (DMEM nutrient solutions), inflammatory model group (LPS), positive controls (dexamethasone+ LPS), experimental group (target compound+LPS).Continue to collect cell supernatant after cultivating 24h, ELISA method is determined in each group culture Interleukin-6 (IL-6) concentration in clear, calculates IL-6 generation inhibiting rates, and formula is as follows：I=(Cm–Ct)/Cm× 100%；Wherein Cm Refer to model group IL-6 concentration, CtRefer to experimental group IL-6 concentration.Using drug concentration as abscissa, inhibiting rate is mapped for ordinate, is obtained Compound concentration (EC when going out 50% inhibiting rate50), the IL-6 that target compound is calculated suppresses EC50It is worth for 47.01 ± 0.12 μM, positive control dexamethasone is 39.13 ± 0.21 μM.

Claims (3)

  1. A kind of 1. novel C separated in Dulong rhizome of Chinese monkshood19- diterpene alkaloid taronenine A, it is characterised in that：Structural formula is：
  2. A kind of 2. C prepared described in claim 119The method of-diterpene alkaloid, it is characterised in that：It uses following steps：
    Step 1：Take Dulong rhizome of Chinese monkshood Aconitum taronense Fletcher et Lauener dried root 6.0kg, powder It is broken；
    Step 2：With 0.5% hydrochloric acid 50L diacolations, reacted to percolate inanimate object alkali, it is 9 then to be alkalized with 10% ammoniacal liquor to pH, Extracted with isometric ethyl acetate, extraction three times, combined ethyl acetate, is concentrated under reduced pressure and drains to obtain total alkaloid medicinal extract 41.5g；
    Step 3：Total alkali medicinal extract is through silica gel column chromatography 100-200 mesh gradient elutions VChloroform:VMethanol, 100:1→1:1, TLC detection is closed And nine part FrA-FrI are obtained, wherein FrD is 9.0g through silica gel column chromatography 300-400 mesh gradient elutions VPetroleum ether:VAcetone:V bis-Ethamine, 100:5:1→100:20:1 isolated target compound 171mg, and its knot is identified by 1D/2D NMR and HR-ESIMS Structure is：
  3. 3. C described in claim 119Application of-the diterpene alkaloid in prevention or treatment anti-inflammatory drugs is prepared.
CN201710801073.4A 2017-09-06 2017-09-06 The novel C separated in the Dulong rhizome of Chinese monkshood19Diterpene alkaloid preparation method and its usage Pending CN107383006A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108912049A (en) * 2018-04-25 2018-11-30 西安医学院 The Diterpenoid Alkaloids compound and preparation method and application extracted from the high rhizome of Chinese monkshood
CN113004297A (en) * 2021-03-08 2021-06-22 沈阳药科大学 Diterpene alkaloid compound and extraction method and application thereof
CN113717105A (en) * 2021-08-09 2021-11-30 沈阳药科大学 Diterpene alkaloid type compound and extraction method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101434580A (en) * 2008-12-24 2009-05-20 西南科技大学 Mesaconitine acylated product nitrous oxide, preparation and use
CN102775349A (en) * 2012-07-02 2012-11-14 云南农业大学 Preparation method for bulleyaconitine A

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101434580A (en) * 2008-12-24 2009-05-20 西南科技大学 Mesaconitine acylated product nitrous oxide, preparation and use
CN102775349A (en) * 2012-07-02 2012-11-14 云南农业大学 Preparation method for bulleyaconitine A

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YUNFENG BI等: "Studies on metabolites and metabolic pathways of bulleyaconitine A in rat liver microsomes using LC-MSn combined with specific inhibitors", 《BIOMEDICAL CHROMATOGRAPHY》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108912049A (en) * 2018-04-25 2018-11-30 西安医学院 The Diterpenoid Alkaloids compound and preparation method and application extracted from the high rhizome of Chinese monkshood
CN108912049B (en) * 2018-04-25 2020-08-11 西安医学院 Diterpene alkaloid compound extracted from aconitum sinomontanum nakai and preparation method and application thereof
CN113004297A (en) * 2021-03-08 2021-06-22 沈阳药科大学 Diterpene alkaloid compound and extraction method and application thereof
CN113004297B (en) * 2021-03-08 2022-03-08 沈阳药科大学 Diterpene alkaloid compound and extraction method and application thereof
CN113717105A (en) * 2021-08-09 2021-11-30 沈阳药科大学 Diterpene alkaloid type compound and extraction method and application thereof

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Application publication date: 20171124