CN109369586A - A kind of onoseriolide sesquiterpene dimers and its preparation method and application - Google Patents

A kind of onoseriolide sesquiterpene dimers and its preparation method and application Download PDF

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CN109369586A
CN109369586A CN201811494784.2A CN201811494784A CN109369586A CN 109369586 A CN109369586 A CN 109369586A CN 201811494784 A CN201811494784 A CN 201811494784A CN 109369586 A CN109369586 A CN 109369586A
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lindenrane
preparation
sesquiterpene dimers
petroleum ether
phase
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CN109369586B (en
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孙振亮
邢欣
虞贞风
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Shanghai University of Medicine and Health Sciences
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Shanghai University of Medicine and Health Sciences
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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Abstract

The present invention provides a kind of onoseriolide sesquiterpene dimers, and structural formula is as follows,

Description

A kind of onoseriolide sesquiterpene dimers and its preparation method and application
Technical field
The invention belongs to field of natural medicinal chemistry, are related to a kind of new compound, specifically a kind of from plant ancient cooking vessel Isolated a kind of onoseriolide sesquiterpene dimers and its preparation method and application in the lindera of lake.
Background technique
Depression (depression) is a kind of disturbance of emotion spirit disease with the lasting low position main feature of mental state Disease, with the aggravation of various stress factors, disease incidence quickly rises.Furthermore depression also with cancer, apoplexy, angiocarpy There is close ties for the various serious diseases such as disease, and pathogenesis is extremely complex, from earliest monoamine hypothesis, arrive inferior colliculus Brain-pituitary-adrenal axis negative reaction is adjusted, then all may be related with the morbidity of depression to mechanism such as nerve cell apoptosis, necrosis. It is also research safety, effective new drug specifies direction with the further investigation of pathogenesis.In recent years, especially there is mind After the research of the natural drug of protective effect obtains certain progress, provided extensively for the clinical drug for obtaining efficient low side effect Wealthy prospect.
Root biomass is the dungarunga or shrub of Lauraceae Lindera plant.Root enlargement is used as medicine, and is distributed mainly on me State Guangdong, Guangxi etc..The plant clinically replaces articles frequently as " root of three-nerved spicebush ", has longer medicinal history.Property is pungent, Temperature；Return liver, stomach meridian, has effects that wind dispelling insecticide, sore hemostasis.Find it rich in a plurality of types of the research of the platymiscium Sesquiterpenoids.The present invention isolated new sesquiterpene dimers from the Root biomass for originate from Guangdong for the first time, And find that the compound has preferable neuroprotection
Summary of the invention
For above-mentioned technical problem in the prior art, the present invention provides a kind of onoseriolide sesquiterpene dimers and its Preparation method and purposes, described this onoseriolide sesquiterpene dimers and its preparation method and application will solve the prior art In treatment depression effect of drugs is limited, technical problem that side effect is big.
The present invention provides a kind of onoseriolide sesquiterpene dimers, and structural formula is as follows,
The present invention also provides a kind of preparation methods of above-mentioned lindenrane sesquiterpene dimers, include the following steps:
1) the dry root coarse powder of Root biomass (Lindera chunii Merr.) is heated to reflux using ethanol solution and is mentioned It takes 1~5 time, 1~4 hour every time, ethyl alcohol was first recovered under reduced pressure in combined extract, extracting solution, then plus after water dispersion successively use etc. Petroleum ether, ethyl acetate and the extracting n-butyl alcohol of volume respectively obtain petroleum ether phase, ethyl acetate phase and n-butanol phase；
2) thin then by petroleum ether-acetone gradient elution by petroleum ether obtained in step 1) mutually through silica gel column chromatography Layer chromatography is inspected, and 5 components are merged into, and third component is passed through reversed-phase silica gel column chromatography, then passes through methanol-water gradient system System elution, obtains lindenrane sesquiterpene dimers using reverse phase C18 silica gel column chromatography.
It is further that during petroleum ether-acetone gradient elution, the volume ratio variation of petroleum ether and acetone is 100: 0 to 0:100.
It is further that during the elution of methanol-water gradient system, the volume ratio variation of first alcohol and water is from 30:70 To 100:0.
The present invention also provides above-mentioned lindenrane sesquiterpene dimers to reduce cortisone to SY5Y nerve cell in preparation Damaging action drug in purposes.
The present invention is by isolated one new onoseriolide sesquialter in Root biomass (Lindera chunii Merr.) Terpene dimer is named as lindenanolide I.
SY5Y cell is people's neuroma mother cell system, after Retinoic Acid Induced Differentiation.Express catecholaminergic neuron Distinctive tyrosine hydroxylase, dopamine 2 B2 hydroxylase and Dopamine Transporter etc. can be used as in neuroprotection research Good cell model, studying physiological, pharmacological characteristics.In experimental study, pass through the SY5Y nerve of observation cortisone damage The neuroprotection of the cell viability evaluation sample of cell.
The compound of the present invention is isolated from Lauraceae Lindera plant Root biomass (Lindera chunii Merr.) Root shows that the compound can reduce cortisone to the damaging action of SY5Y nerve cell through external activity experiment.
Specific embodiment
The preparation of 1 lindenanolide I of embodiment
By the dry root coarse powder of Root biomass (5.0kg), mass percent concentration is used to heat (95 for 80% ethyl alcohol DEG C) refluxing extraction 2 times, 2 hours every time, combined extract, extracting solution depressurized (150hPa) and recycles ethyl alcohol, added after water dispersion successively Petroleum ether phase, ethyl acetate phase and n-butanol are respectively obtained with petroleum ether, ethyl acetate and the extracting n-butyl alcohol of isometric (7L) Phase.
Petroleum ether phase medicinal extract is through silica gel column chromatography, petroleum ether-acetone gradient elution (100:0-0:100), thin-layer chromatography inspection Depending on merging into 5 components (1-5).Third component pass through reversed-phase silica gel column chromatography, methanol-water gradient system (30:70-100: 0) lindenanolide I (2.0mg), is obtained using reverse phase C18 silica gel column chromatography, structural formula is as follows,
The technical indicator of above compound is as follows:
White powder；
Specific rotatory power(c 0.3,MeOH)；
Ultraviolet spectra (MeOH): λmax(logε),200(4.44),220(4.15)；
Circular dichroism spectra (MeOH): 200 (Δ ε+12.5), 240 (Δ ε -35.8), 255 (Δ ε+8.04), nm；
Infrared spectroscopy, νmax 3679,2990,2362,1685,1517,1226,1375,1020,752cm-1；
1H and 13C NMR data(CDCl3), it is shown in Table 1,
HRESIMS m/z 597.2475[M+Na]+(calculated value C34H38O8 597.2459)。
The hydrogen spectrum and carbon modal data of 1 lindenanolide I of table
The experiment of 2 neuroprotective activity of embodiment
With the fetal calf serum for being 10% containing concentration of volume percent, penicillin 100U/mL, the DMEM of streptomysin 100U/mL Culture medium, at 37 DEG C, use concentration of volume percent for 5% CO2It is cultivated in the incubator of saturated humidity, wait enter logarithmic growth The SH-SY5Y cell of phase reaches 70% to 80% fusion, is that 0.25% pancreatin digests 2min, Jing Xiaguan with mass percent concentration It is rounded to examine cell, cellular portions hang, and are added terminate digestion with the isometric DMEM complete medium of pancreatin immediately, blown with suction pipe It beats cell on cell to culture bottle wall all to blow and beat, is transferred to 15mL tip centrifuge tube, 1200r/min centrifugation with suction pipe 5min discards supernatant liquid, and cell is resuspended in DMEM culture medium, is passed on the ratio of 1:3.
SH-SY5Y cell concentration about 1 × 10 is adjusted with cell counter5A/mL, every 80 μ L of hole are inoculated in 96 orifice plates, after Continuous culture.After for 24 hours, 10 μ L cortisone, 400 μm of ol/L damages are added in every hole, and the indenanolide for the various concentration matched is added I (12.5,25,50,100 μM), each experimental group are all provided with 3 multiple holes.Culture is terminated after 72h, whole mass concentration is added in every hole For the MTT20 μ L of 5g/L, 37 DEG C, 5%CO2Continue to cultivate 4h in incubator, after the crystallization of bluish violet is formed, inhales and abandon supernatant, often 150 μ L of DMSO is added in hole, and shaking table shakes 10min, sufficiently dissolves the bluish violet crystal in cell, measures 570nm with microplate reader Absorbance value at wavelength calculates proliferation rate.
Above-mentioned lindenrane sesquiterpene dimers compound is by experiment in vitro the study found that the compound can reduce cortex Ketone the results are shown in Table 2 to the damaging action of SY5Y cell.
The influence for the SY5Y cell survival rate that 2 lindenanolide I of table damages cortisone
By being tested above it is found that lindenrane sesquiterpene dimers of the invention can be used as guide's chemical combination of antidepressants Object.

Claims (5)

1. a kind of onoseriolide sesquiterpene dimers, it is characterised in that: its structural formula is as follows,
2. a kind of preparation method of lindenrane sesquiterpene dimers described in claim 1, it is characterised in that include the following steps:
1) by the dry root coarse powder of Root biomass (Lindera chunii Merr.) using ethanol solution heating and refluxing extraction 1~ 5 times, 1~4 hour every time, ethyl alcohol was first recovered under reduced pressure in combined extract, extracting solution, then plus after water dispersion successively used in equal volume Petroleum ether, ethyl acetate and extracting n-butyl alcohol respectively obtain petroleum ether phase, ethyl acetate phase and n-butanol phase；
2) by petroleum ether obtained in step 1) mutually through silica gel column chromatography, then pass through petroleum ether-acetone gradient elution, thin layer color Spectrum is inspected, and 5 components are merged into, and third component is passed through reversed-phase silica gel column chromatography, is then washed by methanol-water gradient system It is de-, lindenrane sesquiterpene dimers are obtained using reverse phase C18 silica gel column chromatography.
3. a kind of preparation method of lindenrane sesquiterpene dimers according to claim 1, it is characterised in that: in petroleum During ether-acetone gradient elution, the volume ratio variation of petroleum ether and acetone is 100:0 to 0:100.
4. a kind of preparation method of lindenrane sesquiterpene dimers according to claim 1, it is characterised in that: in methanol- During water gradient system elutes, the volume ratio variation of first alcohol and water is from 30:70 to 100:0.
The damage of SY5Y nerve cell is made 5. lindenrane sesquiterpene dimers described in claim 1 reduce cortisone in preparation Purposes in drug.
CN201811494784.2A 2018-12-07 2018-12-07 Linderane type sesquiterpene dimer and preparation method and application thereof Active CN109369586B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115850218A (en) * 2023-01-09 2023-03-28 山东大学 Linderane type sesquiterpene dimer and preparation method and application thereof
CN115716813B (en) * 2021-11-03 2024-05-14 四川大学 Linderane sesquiterpene intermediate, linderane sesquiterpene polymer prepared from intermediate and preparation method

Citations (3)

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CN107868068A (en) * 2016-09-23 2018-04-03 中国科学院上海药物研究所 A kind of onoseriolide Dimerized sesquiterpenoids, preparation method and the usage
CN107865865A (en) * 2016-09-23 2018-04-03 中国科学院上海药物研究所 Purposes of a kind of onoseriolide Dimerized sesquiterpenoids in antimalarial agent is prepared

Patent Citations (3)

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CN107868068A (en) * 2016-09-23 2018-04-03 中国科学院上海药物研究所 A kind of onoseriolide Dimerized sesquiterpenoids, preparation method and the usage
CN107865865A (en) * 2016-09-23 2018-04-03 中国科学院上海药物研究所 Purposes of a kind of onoseriolide Dimerized sesquiterpenoids in antimalarial agent is prepared

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115716813B (en) * 2021-11-03 2024-05-14 四川大学 Linderane sesquiterpene intermediate, linderane sesquiterpene polymer prepared from intermediate and preparation method
CN115850218A (en) * 2023-01-09 2023-03-28 山东大学 Linderane type sesquiterpene dimer and preparation method and application thereof

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