CN1660848A - Application of alkaloid in cephalataxus fortunei esters for preventing and curing nematodiasis of plants - Google Patents
Application of alkaloid in cephalataxus fortunei esters for preventing and curing nematodiasis of plants Download PDFInfo
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- CN1660848A CN1660848A CN 200410015466 CN200410015466A CN1660848A CN 1660848 A CN1660848 A CN 1660848A CN 200410015466 CN200410015466 CN 200410015466 CN 200410015466 A CN200410015466 A CN 200410015466A CN 1660848 A CN1660848 A CN 1660848A
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- harringtonine
- nematode
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Abstract
An application of the cephalotaxine ester, especially the harringtonine and homoharringtonine, in preventing and treating the roundworm diseases of plant is disclosed.
Description
Technical field
The present invention relates to Cephalotaxus fortunei ester Alkaloid (Cephalotaxine esters), especially the purposes of harringtonine (Harringtonine) and homoharringtonine (Homoharringtonine) (can be separately with harringtonine or homoharringtonine, the mixture that also available harringtonine, two compounds of homoharringtonine are formed), the purposes of especially preventing and treating plant nematode diseases.
Background technology
Plant nematode is a class frequently seen plants cause of disease insect, and distribution is wide, the host is wide, and production has caused serious harm to agroforestry.Especially closely during the last ten years, the invasion of pine wood nematode (Bursaphelenchus xylophilus) has caused massive losses for the production of forestry of various countries, East Asia (comprising China).The chemistry nematode killing agent is the effective measure of control plant nematode diseases, but chemical nematode killing agent has the shortcoming of high poison, high residue, and life-time service pollutes the environment and underground water source, and can pass through food chain harm humans health.Therefore, the nematode killing agent of efficient, the low toxicity of research and development, low residue is very necessary.
Structure is various because the natural plant product has, biological activity is extensive, easily degraded in environment, so plant is the important source of all kinds of biologically active substances always.20 since the seventies in century, owing to recognize the hazardness of chemical pesticide to environment, pay attention to from plant, seeking natural nematocidal active material in the world gradually, as India, all there is the research report of this respect in countries such as Japan, Italy, the U.S., Britain, but still rest on the preliminary screening stage so far mostly, effective eelworm-killing activity composition of discovery seldom, and is still very remote apart from practical application.China is late to the research starting that plant kills the line active substance, rarely seen fragmentary report.Publication number is that the Chinese invention patent of CN1105512 discloses and a kind ofly kills the method for pine wood nematode with ALOPERINE, but compares with existing chemical nematode killing agent, and ALOPERINE is not had a significance on nematocidal effect intensity.
We have found a kind of cephalotaxus alkaloid in previous work, promptly bridging oxygen Cepholotoxinum (Drupacine) all has stronger killing action to pine wood nematode and root knot nematode, and have applied for patent (application number: 200310112424.9, still unexposed).But compare with chemical nematode killing agent, the nematocidal effect of bridging oxygen Cepholotoxinum is not also had a significant advantage.Therefore, the stronger nematocidal active material of searching effect is still the key of plant-sourced nematode killing agent research and development from plant.
Cephalotaxus fortunei ester Alkaloid (Cephalotaxines ester) is the alkaloid that the class found from Cephalotaxaceae (Cephalotaxaceae) Cephalotaxus (Cephalotaxus) plant has remarkable antitumour activity, and what wherein the most common and antitumous effect was the strongest is harringtonine (harringtonine) and homoharringtonine (Homoharringtonine).
The structure of Cephalotaxus fortunei ester Alkaloid is seen general formula (I):
Wherein the alkaloid of x=2 is harringtonine (Harringtonine); The alkaloid of x=3 is homoharringtonine (Homoharringtonine).
Above-mentioned two kinds of alkaloidal preparations are to be raw material with Cephalotaxus (Cephalotaxus) plant, adopt currently known methods extraction, the separation of routine to obtain (data sees reference: Yang Yun etc. Natural Medicine Chemistry component extraction separation handbook. and Beijing: China Traditional Chinese Medicine Publishing House, 2003.21-23).
Above-mentioned two kinds of alkaloids have been developed to cancer therapy drug and have been used for clinical.
Summary of the invention
The objective of the invention is to develop the Cephalotaxus fortunei ester Alkaloid of general formula (I), the new purposes of harringtonine and homoharringtonine especially, the new purposes that promptly is used to prevent and treat plant nematode diseases.
The present invention relates to the application that described harringtonine of general formula (I) and homoharringtonine are used to prevent and treat plant nematode diseases.
Described harringtonine of general formula of the present invention (I) and homoharringtonine can be separately or the two jointly as effective constituent, add agricultural chemicals to in carrier or the composition, make pesticide preparation, be used to prevent and treat plant nematode diseases.Maybe will contain these two kinds of compositions or contain wherein that a kind of extract, extractive part (as total alkaloids), separated part of cephalotaxus plant of composition add agricultural chemicals to in carrier or the composition, make pesticide preparation, be used to prevent and treat plant nematode diseases.Can adopt the common pesticide formulation and using method.
Described harringtonine of general formula (I) and homoharringtonine have strong cytotoxicity to plant nematode, and the 1mg/mL mass concentration is handled 5 days the line rate of killing of pine wood nematode (Bursaphelenchus xylophilus) and all reached 99.8%.The 1mg/mL mass concentration is dived the stripped toxic action of root nematode (Hirschmanniella oryzae) and Meloidogyne incognita (Meloidogyne incognita) all above 95% to paddy rice.
Described harringtonine of general formula (I) and homoharringtonine show the toxicity test of nematode, to the median lethal concentration (LC of pine wood nematode
50) being respectively 6.7 μ g/mL and 6.5 μ g/mL, its virulence is 3.5 times of ethoprophos (Ethoprop, a kind of chemical nematode killing agent commonly used), is 4 times of bridging oxygen Cepholotoxinum.
Described harringtonine of general formula (I) and homoharringtonine are to the 95% lethal concentration (LC of pine wood nematode
95) be respectively 42.0 μ g/mL and 41.0 μ g/mL, than low 5 times of ethoprophos, lower more than 1.5 times than the bridging oxygen Cepholotoxinum.Illustrate that described harringtonine of general formula (1) and homoharringtonine kill to nematode that activity far is better than chemical nematode killing agent ethoprophos commonly used and known plants is killed line composition bridging oxygen Cepholotoxinum.
The mixture that contains described harringtonine of general formula (I) and homoharringtonine as the Cephalotaxus oliveri total alkaloids, also has strong toxic action to nematode.
Advantage of the present invention:
(1) compare with the plant-sourced nematocidal active material of having found with existing chemical nematode killing agent, harringtonine of the present invention and homoharringtonine are killed the effect of nematode stronger (higher 2.5～5 times than ethoprophos, higher 1.5～3 times than bridging oxygen Cepholotoxinum);
(2) harringtonine of the present invention and homoharringtonine as anticarcinogen clinical application for many years, its security to human body is guaranteed;
(3) harringtonine of the present invention and homoharringtonine are the natural products from plant, degrade easily at occurring in nature, can not form residual, it is used genus " taking from nature; be used for nature " as agricultural chemicals, therefore, harringtonine of the present invention and homoharringtonine are compared with chemical nematode killing agent and are also had low residue and to environment " close friend's " characteristics.
Embodiment
Following experiment and operational instances are further to explanation of the present invention, should not be used as limitation of the present invention.
Embodiment 1: the preparation of harringtonine and homoharringtonine
Cephalotaxus oliveri (Cephalotaxus oliveri) limb meal, with 8 times of amounts, 95% ethanol lixiviate three times, vat liquor concentrates recovery ethanol and gets dense water liquid, add 3mol/L hydrochloric acid and transfer to pH3, filter, filtrate is alkalized to pH9～10 with yellow soda ash, uses chloroform extraction, reclaim chloroform, obtain total alkaloids (yield 0.053%).Total alkaloids adds the dissolving of 4% citric acid water, and acid liquid is transferred pH to 6,7,8,9 successively with saturated sodium carbonate solution again, gets pH6～7 and liang position, pH8～9 with chloroform extraction respectively.Silicagel column is crossed at pH8～9 positions, with chloroform-methanol (98: 2) wash-out, uses the ether recrystallization then, promptly gets harringtonine.Silicagel column is crossed at pH6～7 positions, with the chloroform-methanol gradient elution, each cut is done the thin plate chromatography, be merged into phase-splitting homogeneous turbulence branch, (it is even that silica gel adds equivalent pH5 damping fluid lapping-in with the silica gel partition chromatography with main flow point (measuring maximum parts), add an amount of chloroform again, wet method dress post), with the saturated chloroform wash-out of damping fluid, each flow point is done the thin-layer chromatography inspection, merge, obtain homoharringtonine and harringtonine.
Embodiment 2: the evaluation of harringtonine and homoharringtonine
Harringtonine: molecular formula C
28H
37NO
9Colourless crystallization, mp74～76 ℃ (ether); [α]
25 D-105 ° of (c0.5, CHCl
3).At HPTLC (Kieselgel 60GF
254, Merck) upward consistent with the harringtonine standard substance; With harringtonine standard substance mixed crystallization, fusing point does not descend.IR,
1H NMR and
13The bibliographical information value of C NMR data and harringtonine is coincide.
Homoharringtonine: molecular formula C
29H
39NO
9Colourless crystallization, mp144～146 ℃; [α]
25 D-119 ° of (c0.5, CHCl
3).At HPTLC (Kieselgel 60GF
254, Merck) upward consistent with the homoharringtonine standard substance; With homoharringtonine standard substance mixed crystallization, fusing point does not descend.IR,
1H NMR and
13The bibliographical information value of C NMR data and homoharringtonine is coincide.
Embodiment 3: to the mensuration of pine wood nematode virulence
Harringtonine, homoharringtonine, bridging oxygen Cepholotoxinum and ethoprophos (Ethoprop) granule are dissolved with small amount of acetone, and adding distil water dilutes, and is made into the test solution of different concns (μ g/mL).In the culture dish of diameter 6cm, with PDA culture medium inoculated pestalotia bacteria (Pestalotia sp.), cultivated 5 days at 25 ℃ of constant incubators, cover with plate to mycelia.At the middle little square absorbent cotton piece of placing the about 1cm of a block length, thick about 0.5cm of the culture dish that covers with the pestalotia bacteria mycelia.Draw the test solution of 0.5 milliliter of different concns respectively with microsyringe, inject cotton piece, draw 0.1 milliliter of pine wood nematode (Bursaphelenchus xylophilus) liquid again and add cotton piece central authorities, 4 repetitions are established in every processing, compare with 2% aqueous acetone solution.Cultivated nematode 5 days at 25 ℃ of constant incubators.Substratum in the plate is all poured out,, calculated the calibration mortality ratio of nematode by following formula with the improvement graceful funnel method of shellfish (Baermann funnel method) separated and collected nematode and counting.
Concentration and corrected mortality by test solution calculate LC by statistical procedures
50Two kinds of alkaloidal line rates extremely of result's (seeing Table 1) demonstration and concentration are closely related, and harringtonine and homoharringtonine are to the median lethal concentration (LC of pine wood nematode
50) to be respectively 6.7 μ g/mL and 6.5 its virulence of μ g/mL are 3.5 times of ethoprophos, are 4 times of bridging oxygen Cepholotoxinum.It is to the 95% lethal concentration (LC of pine wood nematode
95) be respectively 42.0 μ g/mL and 41.0 μ g/mL, than low 5 times of ethoprophos, lower more than 1.5 times than the bridging oxygen Cepholotoxinum.Illustrate that harringtonine and homoharringtonine kill to nematode that activity far is better than chemical nematode killing agent ethoprophos commonly used and known plants is killed line composition bridging oxygen Cepholotoxinum.
Table 1. harringtonine and homoharringtonine are to the cytotoxicity of pine wood nematode
| For test agent | ????LC 50(μg/mL) | ????LC 5095% fiducial limit (μ g/mL) | ??LC 95(μg/mL) |
| Harringtonine homoharringtonine ethoprophos (Ethoprop) bridging oxygen Cepholotoxinum | ????6.7 ????6.5 ????27.1 ????23.2 | ????6.63～6.78 ????6.61～6.75 ????26.6～27.6 ????22.9～23.5 | ??42.0 ??41.0 ??254.1 ??111.1 |
Cytotoxicity to pine wood nematode under the embodiment 4:1mg/mL concentration is measured
Harringtonine, homoharringtonine, Cephalotaxus oliveri total alkaloids (containing harringtonine 36%, homoharringtonine 24% approximately) and bridging oxygen Cepholotoxinum are dissolved with small amount of acetone, adding distil water is diluted to 1mg/mL concentration, method with embodiment 3 is measured corrected mortality, and the result: harringtonine, homoharringtonine, Cephalotaxus oliveri total alkaloids and bridging oxygen Cepholotoxinum are 99.8%, 99.8%, 98.5% and 98.2% to the corrected mortality of pine wood nematode.
Embodiment 5: the cytotoxicity to the latent root nematode of paddy rice is measured
Harringtonine, homoharringtonine and bridging oxygen Cepholotoxinum are dissolved with small amount of acetone, and adding distil water is diluted to 3mg/mL concentration.Get 24 porocyte plates, latent root nematode (Hirschmanniella oryzae) suspension (50～100 nematode) of 100 μ L paddy rice is injected in the sample well, add 100 μ L sterilized waters, add 100 μ l sample solutions again, mix, with 2% aqueous acetone solution is blank, and placing 22～24 ℃, humidity is 80%～90% incubator, 3 repetitions of every processing.Handle the nematode death condition that the back was checked the group that each is handled in 24,48,72 hours respectively, press the formula calculation correction mortality ratio of embodiment 3, the result shows that harringtonine, homoharringtonine and bridging oxygen Cepholotoxinum act on 72 hours corrected mortalities to the latent root nematode of paddy rice and be respectively 96.8%, 97.4% and 89.5% under 1mg/mL concentration.
Embodiment 6: the cytotoxicity to Meloidogyne incognita is measured
Press the method for embodiment 5 and measure harringtonine, homoharringtonine and bridging oxygen Cepholotoxinum cytotoxicity Meloidogyne incognita (Meloidogyne incognita).The result shows that harringtonine, homoharringtonine and bridging oxygen Cepholotoxinum act on 72 hours corrected mortalities to southern root nematode and be respectively 98.9%, 99.4% and 97.3% under 1mg/mL concentration.
Claims (1)
1. the compound of following general formula (I):
X is 2 or 3 in the formula, is used to prevent and treat the application of plant nematode diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410015466 CN1259320C (en) | 2004-02-27 | 2004-02-27 | Application of alkaloid in cephalataxus fortunei esters for preventing and curing nematodiasis of plants |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410015466 CN1259320C (en) | 2004-02-27 | 2004-02-27 | Application of alkaloid in cephalataxus fortunei esters for preventing and curing nematodiasis of plants |
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| CN1259320C CN1259320C (en) | 2006-06-14 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102633806A (en) * | 2012-04-05 | 2012-08-15 | 贵州博丰生物科技产业开发有限公司 | Extraction and separation method of harringtonine |
| WO2013023620A1 (en) * | 2011-08-18 | 2013-02-21 | 杭州本生药业有限公司 | Aminated derivative of homoharringtonine, preparation method therefor, and application thereof |
| CN103141521A (en) * | 2013-02-06 | 2013-06-12 | 杨凌农科大无公害农药研究服务中心 | Cephalotaxus sinensis Li. insecticide and its preparation method |
| CN103687859A (en) * | 2011-08-18 | 2014-03-26 | 杭州本生药业有限公司 | Aminated derivative of homoharringtonine, preparation method therefor, and application thereof |
-
2004
- 2004-02-27 CN CN 200410015466 patent/CN1259320C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013023620A1 (en) * | 2011-08-18 | 2013-02-21 | 杭州本生药业有限公司 | Aminated derivative of homoharringtonine, preparation method therefor, and application thereof |
| CN103687859A (en) * | 2011-08-18 | 2014-03-26 | 杭州本生药业有限公司 | Aminated derivative of homoharringtonine, preparation method therefor, and application thereof |
| CN103687859B (en) * | 2011-08-18 | 2016-08-17 | 杭州本生药业有限公司 | The amination derivant of homoharringtonine, and its preparation method and application |
| US9676789B2 (en) | 2011-08-18 | 2017-06-13 | Hangzhou Bensheng Pharmaceutical Co., Ltd. | Aminated derivative of homoharringtonine, preparation method therefor, and application thereof |
| CN102633806A (en) * | 2012-04-05 | 2012-08-15 | 贵州博丰生物科技产业开发有限公司 | Extraction and separation method of harringtonine |
| CN103141521A (en) * | 2013-02-06 | 2013-06-12 | 杨凌农科大无公害农药研究服务中心 | Cephalotaxus sinensis Li. insecticide and its preparation method |
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| Publication number | Publication date |
|---|---|
| CN1259320C (en) | 2006-06-14 |
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