CN101575342B - 2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide - Google Patents
2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide Download PDFInfo
- Publication number
- CN101575342B CN101575342B CN2009100217474A CN200910021747A CN101575342B CN 101575342 B CN101575342 B CN 101575342B CN 2009100217474 A CN2009100217474 A CN 2009100217474A CN 200910021747 A CN200910021747 A CN 200910021747A CN 101575342 B CN101575342 B CN 101575342B
- Authority
- CN
- China
- Prior art keywords
- podophyllotoxin
- aromatic acid
- acid ester
- acid
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 CCOC(C)O[C@]([C@@](CO1)[C@@]([C@](c(cc2OC)cc(*)c2OC)c2c3)C1=O)c2cc1c3OCO1 Chemical compound CCOC(C)O[C@]([C@@](CO1)[C@@]([C@](c(cc2OC)cc(*)c2OC)c2c3)C1=O)c2cc1c3OCO1 0.000 description 2
- VXEBTGXUHQZNQM-WBCYEJBOSA-N COc(cc([C@@H]([C@H]([C@H](CO1)[C@H]2O)C1=O)c1c2cc2OCOc2c1)cc1C=O)c1OC Chemical compound COc(cc([C@@H]([C@H]([C@H](CO1)[C@H]2O)C1=O)c1c2cc2OCOc2c1)cc1C=O)c1OC VXEBTGXUHQZNQM-WBCYEJBOSA-N 0.000 description 1
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N Cc1cccc(C(O)=O)c1 Chemical compound Cc1cccc(C(O)=O)c1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N OC(c1cc(Cl)ccc1)=O Chemical compound OC(c1cc(Cl)ccc1)=O LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
Images
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a series of new 2beta-chloropodophyllotoxin aromatic acid ester compounds, a preparation method and application in preparing botanical pesticide by using the compounds. Chemical general formulas of the 2beta-chloropodophyllotoxin aromatic acid ester compounds are as figures. The series of compounds are prepared by using podophyllotoxin as a raw material, the material is prepared into 2beta-chloropodophyllotoxin through C-4 site hydroxy group protection, C-2 site beta-chloro substitution and C-4 site protection removal, and then the 2beta-chloropodophyllotoxin reacts with eight aromatic acids to form the 2beta-chloropodophyllotoxin aromatic acid ester compounds. Proved by experiments, the 2beta-chloropodophyllotoxin aromatic acid ester compounds of the invention have good insecticidal activities which are partially higher than that of podophyllotoxin, and the insecticidal activities of some compounds are higher than those of the prior commercial botanical pesticide toosendanin; and proved by the experiments, the compounds can be used for preparing the botanical pesticide with high efficiency and low toxicity.
Description
Technical field
The present invention relates to 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds that series has insecticidal activity, relate in particular to 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds and preparation method, and the application in the preparation plant insecticide.
Background technology
Podophyllotoxin is the plant secondary substance that extraction separation comes out from the sandy ground cypress, and antitumor because of having, antiviral, antimycotic isoreactivity receives much concern, but toxic side effect is big.In recent years, it is found that it is to the multiple agriculture and forestry injurious insect restraining effect that has food refusal, kills and grow.
Antitumor and the insecticidal activity of podophyllotoxin and derivative has bibliographical information, as: document [Margaret B.Glinski, James C.Freed, and Tony Durst.Preparation of2-Substituted Podophyllotoxin Derivatives.The Journal of Organic Chemstry.1987,52,2749-2753] reported that 2 β-chloro podophyllotoxin has the good in-vitro anti-tumor activity; Document [Tian Xuan, Gao Rong, Zhang Xing, similar thing structure of podophyllotoxin and insecticidal activity concern that pre-test II structure activity relationship is analyzed and ideal structure is inferred, Northwest Agricultural University's journal, 2000,28 (6): 19-24.] reported that the Podophyllum emodi var chinense derivatives active of the trans lactonic ring of tool is significantly higher than the derivative of tool cis lactonic ring, 4 bit substituents are bigger to the insecticidal activity influence; [woods Jin, Ma Zhiqing, Feng Juntao, Zhang Xing, podophyllotoxin and deoxidation podophyllotoxin be to mythimna separata biological activity preliminary study, northwest agricultural journal, 2005,14 (1): 94-97 for document.] reported that podophyllotoxin has very strong insecticidal activity to mythimna separata, it is grown also has restraining effect simultaneously, and causing grows respectively goes through the phase and all postpones, and percentage of pupation, eclosion rate, egg laying amount etc. all obviously reduce.But the research synthetic and aspect insecticidal activity of 2 β-chloro podophyllotoxin derivative yet there are no report.
Summary of the invention
The objective of the invention is to, provide 2 new beta-chloropodophyllotoxiaromatic aromatic acid ester compounds of series, and provided the preparation method of compound.According to experiment showed, that 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds have the insecticidal activity of high-efficiency low-toxicity, can be used in the preparation plant insecticide.
For realizing above-mentioned task, the present invention is achieved by following technical measures:
A series of 2 new beta-chloropodophyllotoxiaromatic aromatic acid ester compounds is characterized in that the chemical general formula of this 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds is:
Above-mentioned 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds, wherein C-2 position chlorine is substituted by beta comfiguration, and C-4 bit substituent R is respectively:
The preparation method of above-mentioned 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds, it is characterized in that, with a certain amount of 2 β-chloro podophyllotoxin, aromatic acid is dissolved in the dichloromethane solvent with an amount of 4-Dimethylamino pyridine, at room temperature add an amount of dewatering agent N after the stirred for several minute, N '-DIC, place room temperature reaction then, TLC follows the tracks of detection, reaction finishes after-filtration, remove di-isopropyl urea solid, use dichloromethane extraction after adding less water in the filtrate, uses anhydrous sodium sulfate drying after merging organic phase, behind the concentrated evaporate to dryness with the preparation silica gel thin sheet separate required pure product.
The preparation method of described 2 β-chloro podophyllotoxin is as follows:
With mixing solutions (volume ratio is 1/9) the hydrolysis 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin of concentrated hydrochloric acid and tetrahydrofuran (THF), TLC follows the tracks of detection.After treating that hydrolysis reaction finishes, the sodium bicarbonate neutralization with 5%, adjust pH to 5.Remove tetrahydrofuran (THF) under reduced pressure, use dichloromethane extraction 3 times, merge organic phase.Use 5% sodium bicarbonate successively, the saturated common salt water washing.Anhydrous sodium sulfate drying, concentrate evaporate to dryness after silica gel column chromatography separate required pure product.
The preparation method of described 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin is as follows:
Under argon shield, Diisopropylamine is added drop-wise to makes N-Lithiodiisopropylamide (LDA) in the n-Butyl Lithium tetrahydrofuran solution, then with liquid nitrogen-ethyl acetate be chilled to-84 ℃ standby.
4-O-tetrahydropyrans podophyllotoxin is dissolved in a spot of dry tetrahydrofuran, joins at leisure then in N-Lithiodiisopropylamide (LDA) solution for preparing previously, obtain the tetrahydrofuran solution of yellow transparent, stirred 15 minutes at-84 ℃.
Hexachloroethane is added in the tetrahydrofuran solution of the yellow transparent that obtains above, under agitation return to room temperature, TLC follows the tracks of detection.After reaction is finished, steam to remove tetrahydrofuran (THF) through underpressure distillation, with the methylene dichloride dilution, water successively, 0.1mol/L HCl, water washing, anhydrous sodium sulfate drying, concentrate evaporate to dryness after silica gel column chromatography separate required pure product.
The preparation method of described 4-O-tetrahydropyrans podophyllotoxin is as follows:
Take by weighing podophyllotoxin and be dissolved in the dihydropyrane, and drip several phosphorus oxychloride, after in 60-63 ℃ water-bath, dissolving, stirring reaction under the room temperature, TLC follows the tracks of detection.Reaction is basic fully the time, behind the intact dihydropyrane of underpressure distillation evaporate to dryness unreacted, through silica gel column chromatography separate pure product.
Above-mentioned aromatic acid is: naphthylacetic acid, 3,5-dinitrobenzoic acid, M-NITROBENZOIC ACID, p-methylbenzoic acid, m-methyl benzoic acid, 0-chloro-benzoic acid, toluylic acid, m-chlorobenzoic acid are wherein a kind of.
The experiment proved that 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds of the present invention have cytotoxicity to the agriculture and forestry injurious insect mythimna separata, and the activity of part of compounds is higher than the botanical pesticide Toosendanin that has now gone on the market, can be used for preparing good plant insecticide.
Description of drawings
Fig. 1, Fig. 2, Fig. 3, the mass spectrum that is respectively compound 1, hydrogen spectrum and infared spectrum.
Below the embodiment that provides by accompanying drawing and contriver the present invention done further elaborate.
Embodiment
The present invention has synthesized serial 2 new beta-chloropodophyllotoxiaromatic aromatic acid ester compounds, and has carried out the research of further insecticidal activity.The result shows that 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds have stronger food refusal cytotoxicity to the agriculture and forestry injurious insect mythimna separata, can be used for preparing the plant insecticide of high-efficiency low-toxicity.
Below be the embodiment that the contriver provides.
Embodiment 1:
The physico-chemical property of one, product: 2 β-chloro podophyllotoxin and each compound of compound 1-8 describes in detail in following content.
Two, preparation method:
Below be the synthetic route of 4-O-tetrahydropyrans podophyllotoxin:
Take by weighing the 1mmol podophyllotoxin and be dissolved in the 10mL dihydropyrane, drip 1 phosphorus oxychloride, after in 60-63 ℃ water-bath, dissolving, stirring reaction under the room temperature, TLC follows the tracks of detection.Reaction is basic fully the time, behind the intact dihydropyrane of underpressure distillation evaporate to dryness unreacted, through silica gel column chromatography separate pure product.
Podophyllotoxin 4-O-tetrahydropyrans podophyllotoxin
The physico-chemical property of 4-O-tetrahydropyrans podophyllotoxin is as follows:
1), white solid, fusing point 93-94 ℃.
2), the infrared spectrogram of 4-O-tetrahydropyrans podophyllotoxin (IR) feature:
Adopt pellet technique: 2939,2831cm
-1For hydrocarbon stretching vibration absorbs, 1775cm
-1Be lactonic ring carbonyl absorption, 1587,1503,1480cm
-1Be aromatic ring frame absorption of vibrations, 1235,1122cm
-1For (C-O-C) absorbs, 930cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of 4-O-tetrahydropyrans podophyllotoxin (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.18 (s, 1/2H, H-5), 6.91 (s, 1/2H, H-5), 6.51 (s, 1H, H-8), 6.39 (s, 2H, H-2 ', 6 '), 5.96 (m, 2H, OCH
2O), 4.92 (d, J=9.6Hz, 1H, H-4), 4.56 (m, 3H, H-1, H-11and 2 "), 3.97 (m, 1H, H-11), 3.89 (m, 1H, H-6 "), 3.78 (s, 3H, 4 '-OCH
3), 3.73 (s, 6H, 3 ', 5 '-OCH
3), 3.52 (m, 1H, H-6 "), 2.82 (m, 2H, H-2,3), 1.87-1.56 (m, 6H, H-3 ", 4 ", 5 ").
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 521.
Below be the synthetic route of 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin:
Under argon shield, the Diisopropylamine of 1.4mmol is added drop-wise in the tetrahydrofuran solution of 1.2mmol n-Butyl Lithium (10mL), make N-Lithiodiisopropylamide (LDA), with liquid nitrogen-ethyl acetate be chilled to-84 ℃ standby.The 4-O-tetrahydropyrans podophyllotoxin of 1mmol is dissolved in a spot of dry tetrahydrofuran, joins at leisure then in the LDA solution for preparing previously, obtain the tetrahydrofuran solution of yellow transparent.Behind-84 ℃ of stirring 15min, obtain in the tetrahydrofuran solution of yellow transparent above the hexachloroethane adding with 1.4mmol.Under agitation return to room temperature, TLC follows the tracks of detection.Reaction is when finishing, steam through underpressure distillation and remove tetrahydrofuran (THF), with the dilution of 50ml methylene dichloride, water successively, 0.1mol/L HCl, water washing (1 * 30ml), use anhydrous sodium sulfate drying, concentrated evaporate to dryness after silica gel column chromatography separate required pure product.
4-O-tetrahydropyrans podophyllotoxin 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin
The physico-chemical property of 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin is as follows:
1), white solid, fusing point 85-88 ℃.
2), infrared spectrogram (IR) feature of 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin:
Adopt pellet technique: 2939,2838cm
-1For hydrocarbon stretching vibration absorbs, 1785cm
-1Be lactonic ring carbonyl absorption, 1588,1503,1482cm
-1Be aromatic ring frame absorption of vibrations, 1235,1124cm
-1For (C-O-C) absorbs, 932cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.22 (s, 1/2H, H-5), 6.91 (s, 1/2H, H-5), 6.50 (s, 1H, H-8), 6.43 (s, 2H, H-2 ', 6 '), 5.98 (m, 2H, OCH
2O), 5.06 (d, J=9.2Hz, 1H, H-4), 4.74 (m, 2H, H-1and H-2 "), 4.53 (m, 1H, H-11), 4.34 (m, 1H, H-11), 3.91 (m, 1H, H-6 "), 3.82 (s, 3H, 4 '-OCH
3), 3.69 (s, 6H, 3 ', 5 '-OCH
3), 3.53 (m, 1H, H-6 "), 3.01 (m, 1H, H-3), 1.94-1.56 (m, 6H, H-3 ", 4 ", 5 ").
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 555,557.
Below be the synthetic route of 2 β-chloro podophyllotoxin:
With mixing solutions (volume ratio is 1/9) the hydrolysis 4-O-tetrahydropyrans podophyllotoxin of 40ml concentrated hydrochloric acid and tetrahydrofuran (THF), TLC follows the tracks of detection.After treating that the water reaction finishes, the sodium bicarbonate neutralization with 5%, adjust pH to 5.Remove tetrahydrofuran (THF) under reduced pressure, and the usefulness dichloromethane extraction (3 * 30ml), merge organic phase.Use 5% sodium bicarbonate successively, saturated common salt water washing (1 * 30ml).Use anhydrous sodium sulfate drying, concentrate evaporate to dryness after silica gel column chromatography separate required pure product.
4-O-tetrahydropyrans-2 β-chloro podophyllotoxin 2 β-chlorine podophyllotoxin
The physico-chemical property of 2 β-chloro podophyllotoxin is as follows:
1), white solid, fusing point 186-187 ℃.
2), infrared spectrogram (IR) feature of 2 β-chloro podophyllotoxin:
Adopt pellet technique: 2938,2903cm
-1For hydrocarbon stretching vibration absorbs, 1783cm
-1Be lactonic ring carbonyl absorption, 1589,1503,1482cm
-1Be aromatic ring frame absorption of vibrations, 1235,1122cm
-1For (C-O-C) absorbs, 932cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of 2 β-chloro podophyllotoxin (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.10 (s, 1H, H-5), 6.52 (s, 1H, H-8), 6.41 (s, 2H, H-2 ', 6 '), 5.98 (m, 2H, OCH
2O), 4.96 (d, J=7.2Hz, 1H, H-4), 4.77 (s, 1H, H-1), 4.57 (m, 1H, H-11), 4.34 (m, 1H, H-11), 3.82 (s, 3H, 4 '-OCH
3), 3.69 (s, 6H, 3 ', 5 '-OCH
3), 3.01 (m, 1H, H-3), 2.34 (s, 1H ,-O
H).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 471,473.
Below be the synthetic route of compound 1-8:
0.25mmol 2 β-chloro podophyllotoxin, 0.35mmol aromatic acid and 0.05mmol 4-Dimethylamino pyridine are dissolved in the 10ml exsiccant dichloromethane solvent, behind stirring at room number minute, add 0.35mmol dewatering agent N, N '-DIC, room temperature reaction then, TLC follows the tracks of detection, reaction finishes after-filtration, removes di-isopropyl urea solid.Add 25ml water in the filtrate, with methylene dichloride (4 * 30ml) extractions use anhydrous sodium sulfate drying after merging organic phase, behind the concentrated evaporate to dryness with the preparation silica gel thin sheet separate required pure product.
Reaction expression is as follows:
Compound 1:
The physico-chemical property of this compound is as follows:
1), white solid, fusing point 200-203 ℃, specific rotatory power [α]
20 D=-147 ° (C=0.56mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2919cm
-1For hydrocarbon stretching vibration absorbs, 1776,1736cm
-1Be carbonyl absorption, 1596,1505,1484cm
-1Be aromatic ring frame absorption of vibrations, 1236,1127cm
-1For (C-O-C) absorbs, 937cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.98 (d, J=8.0Hz, 1H, naphthalene ring), (7.88 d, J=7.2Hz, 1H, naphthalene ring), 7.82 (dd, J=2.8,6.8Hz, 1H, naphthalene ring), 7.53 (m, 2H, naphthalene ring), (7.41 m, 2H, naphthalene ring), 6.54 (s, 1H, H-5), 6.48 (s, 1H, H-8), 6.32 (s, 2H, H-2 ', 6 '), 5.97 (m, 3H, H-4and OCH
2O), 4.71 (s, 1H, H-1), 4.35 (m, 1H, H-11), 4.19 (s, 2H, C
H 2C
10H
7), 4.05 (m, 1H, H-11), 3.78 (s, 3H, 4 '-OCH
3), 3.63 (s, 6H, 3 ', 5 '-OCH
3), 2.93 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 639,641.
5), reaction formula is:
The mass spectrum of compound 1, hydrogen spectrum and infared spectrum are referring to shown in Fig. 1,2,3.
Compound 2:
The physico-chemical property of this compound is as follows:
1), yellow solid, fusing point 142-145 ℃, specific rotatory power [α]
20 D=-90 ° (C=0.26mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2923cm
-1For hydrocarbon stretching vibration absorbs, 1778,1732cm
-1Be carbonyl absorption, 1590,1493,1464cm
-1Be aromatic ring frame absorption of vibrations, 1245,1119cm
-1For (C-O-C) absorbs, 927cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is δ: 9.30 (s, 1H, H-4 "), 9.15 (s, 2H, H-2 ", 6 "); 6.82 (s, 1H, H-5), 6.64 (s, 1H, H-8), 6.50 (s, 2H, H-2 '; 6 '), 6.35 (d, J=8.8Hz, 1H, H-4), 6.04 (d, 2H, OCH
2O), 4.86 (s, 1H, H-1), 4.62 (m, 1H, H-11), 4.41 (m, 1H, H-11), 3.75 (s, 9H, 3 ', 4 ', 5 '-OCH
3), 3.31 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 665,667.
5) reaction formula is:
Compound 3:
The physico-chemical property of this compound is as follows:
1), yellow solid, 9698 ℃ of fusing points, specific rotatory power [α]
20 D=-103 ° (C=0.38mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2936cm
-1For hydrocarbon stretching vibration absorbs, 1786,1726cm
-1Be carbonyl absorption, 1588,1532,1504cm
-1Be aromatic ring frame absorption of vibrations, 1237,1123cm
-1For (C-O-C) absorbs, 932cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 8.82 (s, 1H, H-2 "), 8.40 (d; J=7.6Hz, 2H, H-4 ", 6 "), 7.72 (m; J=8.0Hz, 1H, H-5 "), 6.86 (s, 1H, H-5), 6.62 (s, 1H, H-8), 6.50 (s, 2H, H-2 ', 6 '), 6.28 (d, J=9.2Hz, 1H, H-4), 6.03 (d, 2H, OCH
2O), 4.85 (s, 1H, H-1), 4.60 (m, 1H, H-11), 4.42 (m, 1H, H-11), 3.80 (s, 9H, 3 ', 4 ', 5 '-OCH
3), 3.24 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 620,622.
5), reaction formula is:
Compound 4:
The physico-chemical property of this compound is as follows:
1), white solid, fusing point 92-94 ℃, specific rotatory power [α]
20 D=-108 ° (C=0.36mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2917cm
-1For hydrocarbon stretching vibration absorbs, 1784,1720cm
-1Be carbonyl absorption, 1588,1504,1485cm
-1Be aromatic ring frame absorption of vibrations, 1239,1122cm
-1For (C-O-C) absorbs, 929cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.91 (d, J=8.0Hz, 2H, H-2 ", 6 "), 7.26 (d, J=2.8Hz, 5H, H-3 ", 5 " and 4 "-C
H 3), 6.91 (s, 1H, H-5), 6.59 (s, 1H, H-8), 6.49 (s, 2H, H-2 ', 6 '), 6.18 (d, J=9.2Hz, 1H, H-4), 6.00 (d, 2H, OCH
2O), 4.83 (s, 1H, H-1), 4.63 (m, 1H, H-11), 4.44 (m, 1H, H-11), 3.71 (s, 9H, 3 ', 4 ', 5 '-OCH
3), 3.23 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 589,591.
5), reaction formula is:
Compound 5:
The physico-chemical property of this compound is as follows:
1), white solid, fusing point 116-119 ℃, specific rotatory power [α]
20 D=-128 ° (C=0.33mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2931cm
-1For hydrocarbon stretching vibration absorbs, 1786,1735cm
-1Be carbonyl absorption, 1588,1503,1484cm
-1Be aromatic ring frame absorption of vibrations, 1237,1124cm
-1For (C-O-C) absorbs, 934cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.83 (s, 2H, H-2 ", 6 "), 7.43 (d, J=7.2Hz, 1H, H-5 "), 7.36 (m; J=8.0Hz, 1H, H-4 "), 6.91 (s, 1H, H-5), 6.60 (s, 1H, H-8), 6.50 (s, 2H, H-2 ', 6 '), 6.21 (d, J=8.8Hz, 1H, H-4), 6.00 (d, 2H, OCH
2O), 4.83 (s, 1H, H-1), 4.61 (m, 1H, H-11), 4.43 (m, 1H, H-11), 3.80 (s, 9H, 3 ', 4 ', 5 '-OCH
3), 3.26 (m, 1H, H-3), 2.41 (s, 3H, 3 " C
H 3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 589,591.
5), reaction formula is:
Compound 6:
The physico-chemical property of this compound is as follows:
1), white solid, fusing point 202-205 ℃, specific rotatory power [α]
20 D=-121 ° (C=0.30mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2929cm
-1For hydrocarbon stretching vibration absorbs, 1781,1731cm
-1Be carbonyl absorption, 1590,1502,1482cm
-1Be aromatic ring frame absorption of vibrations, 1235,1122cm
-1For (C-O-C) absorbs, 925cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.85 (d, J=8.0Hz, 1H, H-6 "), 7.49 (m, 2H, H-3 ", 5 "); 7.35 (m, 1H, H-4 "), 6.94 (s, 1H, H-5), 6.58 (s, 1H, H-8), 6.47 (s, 2H, H-2 ', 6 '), 6.28 (d, J=9.2Hz, 1H, H-4), 6.00 (d, 2H, OCH
2O), 4.82 (s, 1H, H-1), 4.63 (m, 1H, H-11), 4.49 (m, 1H, H-11), 3.74 (s, 3H, 4 '-OCH
3), 3.68 (s, 6H, 3 ', 5 '-OCH
3), 3.30 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 609,611,613.
5), reaction formula is:
Compound 7:
The physico-chemical property of this compound is as follows:
1), white solid, fusing point 88-91 ℃, specific rotatory power [α]
20 D=-150 ° (C=0.54mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2923cm
-1For hydrocarbon stretching vibration absorbs, 1780,1735cm
-1Be carbonyl absorption, 1589,1503,1483cm
-1Be aromatic ring frame absorption of vibrations, 1235,1124cm
-1For (C-O-C) absorbs, 935cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.36-7.26 (m, 5H, H-2 ", 3 ", 4 " and, 5 ", 6 "), 6.68 (s, 1H, H-5), 6.52 (s, 1H, H-8), 6.39 (s, 2H, H-2 ', 6 '), 5.98 (m, 3H, H-4and OCH
2O), 4.75 (s, 1H, H-1), 4.41 (m, 1H, H-11), 4.19 (m, 1H, H-11), 3.81-3.67 (s, 11H, 3 ', 4 ', 5 '-OCH
3And C
6H
5C
H 2); 3.03 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 589,591.
5), reaction formula is:
Compound 8:
The physico-chemical property of this compound is as follows:
1), white solid, 82 ℃-84 ℃ of fusing points, specific rotatory power [α]
20 D=-99 ° (C=0.71mg/mL, chloroform);
2), the infrared spectrogram of this compound (IR) feature:
Adopt pellet technique: 2934cm
-1For hydrocarbon stretching vibration absorbs, 1783,1722cm
-1Be carbonyl absorption, 1589,1504,1484cm
-1Be aromatic ring frame absorption of vibrations, 1239,1123cm
-1For (C-O-C) absorbs, 933cm
-1Be (OCH
2O-) absorb.
3), the nuclear magnetic resonance map of this compound (
1HNMR, 400MHz) feature:
With the deuterochloroform is solvent, and TMS is interior mark, and wherein each peak ownership is: δ: 7.98 (s, 1H, H-2 "), 7.93 (d; J=8.0Hz, 1H, H-6 "), 7.60 (d, J=7.6Hz, 1H, H-4 "), 7.42 (m, 1H, H-5 "), 6.88 (s, 1H, H-5), 6.60 (s, 1H, H-8), 6.49 (s, 2H, H-2 ', 6 '), 6.29 (d, J=9.2Hz, 1H, H-4), 6.01 (d, 2H, OCH
2O), 4.83 (s, 1H, H-1), 4.61 (m, 1H, H-11), 4.42 (m, 1H, H-11), 3.71 (s, 9H, 3 ', 4 ', 5 '-OCH
3), 3.25 (m, 1H, H-3).
4), ESI-TRAP source mass spectrum (MS) the figure feature of this compound: its [M+Na]
+The peak is 609,611,613.
5), reaction formula is:
Embodiment 2:
Of the present invention giving birth to surveyed experiment:
1, for the examination insect: 3 ages are armyworm larvae in earlier stage, is provided by insectary, Xibei Univ. of Agricultural ﹠ Forest Science ﹠ Technology public nuisance-free agricultural chemicals research centre.
2, sample and reagent:
Sample is: the compound 1-8 of Toosendanin, podophyllotoxin, 4-O-tetrahydropyrans podophyllotoxin, 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin, 2 β-chloro podophyllotoxin and embodiment 1 preparation.Solvent is an acetone, the Long Huagongshijichang of Chengdu section, analytical pure.
3, give birth to the survey method:
Adopt leaflet butterfly additive process: at diameter is shop, culture dish bottom one deck filter paper of 9 centimetres, and adds water and preserve moisture.The armyworm larvae in early stage in 3 ages that 10 sizes of every ware picking are consistent, healthy and strong.Take by weighing 5mg Toosendanin, podophyllotoxin, 4-O-tetrahydropyrans podophyllotoxin, 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin, 2 β-chloro podophyllotoxin and compound 1-8 respectively, add 5ml acetone, be made into the soup that concentration is 1mg/ml.Leaf of Semen Maydis is cut into 1 * 1 centimetre little leaf butterfly, in soup to be measured, soaked 3 seconds, dry the back and feed the examination worm.With the acetone solution is the blank group.10 of every processing repeat 3 times.In under the room temperature (about 25 ℃), humidity 65%～80%, light application time is to raise under 12 hours/day the condition.Feed with normal leaf butterfly until emergence after 48 hours.The food ingestion of periodic logging insect, survivor of a murder attempt's number, reveal any symptoms etc. calculate examination 24 hours, 48 hours food refusal rate of worm and final mortality ratio according to following formula.Measurement result sees Table 1.
Food refusal rate (%)=(the average food ingestion of the average food ingestion-treatment group of control group)/(the average food ingestion of control group) * 100
Final mortality ratio (%)=(the dead number of examination worm)/(the total number of examination worm) * 100
Correct mortality ratio (%)=(handling mortality ratio-contrast mortality ratio)/(1-contrasts mortality ratio) * 100
Table 1 the present invention 2 β-chlorine podophyllotoxin derivative 1-8 to 3 age mythimna separata the food refusal toxic effect
Conclusion: the result shows, the compound 2 of the present invention's preparation, and the antifeedant activity 24 hours and 48 hours all is higher than podophyllotoxin, and the cytotoxicity of compound 1,3,7 all is higher than Toosendanin and parent compound, can be as the application for preparing plant insecticide.
Claims (7)
1.2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds is characterized in that, its chemical general formula is:
In chemical general formula, C-2 position chlorine is substituted by beta comfiguration, and C-4 bit substituent R is respectively:
2. the preparation method of described 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds of claim 1, it is characterized in that, with quantitative 2 β-chloro podophyllotoxin, aromatic acid is dissolved in an amount of dichloromethane solvent with an amount of 4-Dimethylamino pyridine, at room temperature add dewatering agent N after the stirred for several minute, N '-DIC, place room temperature reaction then, TLC follows the tracks of detection, reaction finishes after-filtration, remove di-isopropyl urea solid, use dichloromethane extraction after adding less water in the filtrate, uses anhydrous sodium sulfate drying after merging organic phase, behind the concentrated evaporate to dryness with the preparation silica gel thin sheet separate required pure product.
3. method as claimed in claim 2, it is characterized in that the preparation method of described 2 β-chloro podophyllotoxin is, is 1/9 formation mixing solutions by volume with concentrated hydrochloric acid and tetrahydrofuran (THF), use this mixing solutions hydrolysis 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin then, TLC follows the tracks of detection; After treating that hydrolysis reaction finishes, the sodium bicarbonate neutralization with 5%, adjust pH to 5; Remove tetrahydrofuran (THF) under reduced pressure, use dichloromethane extraction 3 times, merge organic phase, use 5% sodium bicarbonate successively, the saturated common salt water washing; Anhydrous sodium sulfate drying, concentrate evaporate to dryness after silica gel column chromatography separate required pure product.
4. method as claimed in claim 3 is characterized in that, the preparation method of described 4-O-tetrahydropyrans-2 β-chloro podophyllotoxin is:
1) under argon shield, Diisopropylamine is added drop-wise to makes N-Lithiodiisopropylamide (LDA) in the n-Butyl Lithium tetrahydrofuran solution, then with liquid nitrogen-ethyl acetate be chilled to-84 ℃ standby;
2) 4-O-tetrahydropyrans podophyllotoxin is dissolved in a spot of dry tetrahydrofuran, joins at leisure then in N-Lithiodiisopropylamide (LDA) solution, obtain the tetrahydrofuran solution of yellow transparent, stirred 15 minutes at-84 ℃; Hexachloroethane joined in the xanchromatic tetrahydrofuran (THF) clear solution under agitation return to room temperature, TLC follows the tracks of detection; After reaction is finished, steam to remove tetrahydrofuran (THF) through underpressure distillation, with the methylene dichloride dilution, water successively, 0.1mol/L HCl, water washing, anhydrous sodium sulfate drying, concentrate evaporate to dryness after silica gel column chromatography separate required pure product.
5. method as claimed in claim 4, it is characterized in that, the preparation method of described 4-O-tetrahydropyrans podophyllotoxin is to take by weighing podophyllotoxin and be dissolved in the dihydropyrane, and drip several phosphorus oxychloride, after in 60-63 ℃ water-bath, dissolving, stirring reaction under the room temperature, TLC follows the tracks of detection, when reaction is complete substantially, behind the intact dihydropyrane of underpressure distillation evaporate to dryness unreacted, through silica gel column chromatography separate pure product.
6. method as claimed in claim 2 is characterized in that, described aromatic acid is a naphthylacetic acid, 3, a kind of in 5-dinitrobenzoic acid, M-NITROBENZOIC ACID, p-methylbenzoic acid, m-methyl benzoic acid, 0-chloro-benzoic acid, toluylic acid and the m-chlorobenzoic acid.
7. described 2 beta-chloropodophyllotoxiaromatic aromatic acid ester compounds of claim 1 application that is used to prepare plant insecticide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100217474A CN101575342B (en) | 2009-03-30 | 2009-03-30 | 2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100217474A CN101575342B (en) | 2009-03-30 | 2009-03-30 | 2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101575342A CN101575342A (en) | 2009-11-11 |
| CN101575342B true CN101575342B (en) | 2011-04-20 |
Family
ID=41270432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100217474A Expired - Fee Related CN101575342B (en) | 2009-03-30 | 2009-03-30 | 2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101575342B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093382B (en) * | 2011-02-14 | 2012-10-24 | 西北农林科技大学 | 2alpha or 2beta-bromopodophyllotoxin derivatives, preparation thereof, and application thereof to botanical pesticides |
| CN103554125B (en) * | 2013-10-28 | 2016-06-01 | 西北农林科技大学 | 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications |
-
2009
- 2009-03-30 CN CN2009100217474A patent/CN101575342B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101575342A (en) | 2009-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101497618B (en) | 4'-podophyllotoxin demethyl deoxidated aromatic ester, substituted benzene sulfonate, ether derivative and use in plant source pesticide preparation | |
| CN107711855A (en) | Application of the peaceful alkali A derivatives of camel in the medicine of preventing and treating or anti-plant disease is prepared | |
| CN105884634B (en) | The preparation of gossypol derivative and they, application and anticancer activity on pesticide | |
| CN106866419A (en) | One terpenoid ester compounds and its production and use | |
| CN102453036B (en) | A kind of camptothecine compounds and preparation method thereof and the purposes in agricultural chemicals | |
| PL155723B1 (en) | Pesticide in particular against insects, nematodes and mites | |
| CN101575342B (en) | 2beta-chloropodophyllotoxin aromatic acid ester compounds and application in preparing botanical pesticide | |
| US8258178B2 (en) | Agents for preventing attachment of barnacle consisting of organic solvent extracts of red alga Laurencia sp. and compounds isolated therefrom | |
| CN110818708A (en) | Compound containing fused heterocyclic structure, preparation method and application thereof, and bactericide | |
| CN100334090C (en) | Pyridines podophyllotoxin compounds and their preparation method and use in preparation of pesticides | |
| KR100943836B1 (en) | Biocidal compounds and their preparation | |
| CN110204538B (en) | Aryl thiazole-tryptamine ocean red tide algae algicide and preparation method and application thereof | |
| CN102633805B (en) | Chelerythrine alcoholate, preparation method thereof and application in plant fungicide medicaments | |
| CN109422744A (en) | Matrine derivative and its synthesis and the application in terms of preventing and treating plant pest | |
| CN104370982A (en) | Diphyllin derivatives, and preparation method and application thereof | |
| CN105994314A (en) | Application of Luotonin A to prevention and treatment of aphid | |
| CN105418594A (en) | Compound, preparation method and antibacterial application thereof | |
| CN108285424B (en) | Gossypol Schiff base derivative, preparation and application thereof in resisting plant tobacco mosaic virus | |
| CN103435622B (en) | A kind of spiro indole diketopiperazine Alkaloid and synthetic method thereof and application | |
| CN102265877B (en) | Application of beta-resorcylic acid large ring lactone in controlling harmful snails | |
| CN106831682A (en) | Halogen coumarin derivatives, violent water flea agent for killing, preparation method and applications | |
| CN101434578A (en) | Synthesis and use of mesaconitine esterification derivative and salt thereof | |
| CN103554125B (en) | 4-2 ' (2 ', 6 ') of alpha-acyloxy, 2 ��-many halogen is for podophyllotoxin derivative and Synthesis and applications | |
| CA3194106A1 (en) | Indole alkaloid with fungicidal effect | |
| Karim et al. | Tropical agricultural science |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110420 Termination date: 20130330 |