CN1590388A - Podophyllotoxin series derivative and its application - Google Patents

Podophyllotoxin series derivative and its application Download PDF

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Publication number
CN1590388A
CN1590388A CN 200310105870 CN200310105870A CN1590388A CN 1590388 A CN1590388 A CN 1590388A CN 200310105870 CN200310105870 CN 200310105870 CN 200310105870 A CN200310105870 A CN 200310105870A CN 1590388 A CN1590388 A CN 1590388A
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Prior art keywords
compound
podophyllum emodi
emodi var
var chinense
podophyllotoxin
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Inventor
李广泽
冯俊涛
郝双红
何军
段苓
张兴
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Nuisanceless Pesticide Research Service Center Xibei Agroforestry Science And T
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Nuisanceless Pesticide Research Service Center Xibei Agroforestry Science And T
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Abstract

A series of podophyllotoxin derivatives with insecticiding activity is prepared from podophyllum compound. Its application is also disclosed.

Description

Podophyllotoxin series derivates and application thereof
One, technical field:
The present invention relates to a kind of podophyllotoxin analogue of tool insecticidal activity, especially relate to a kind of podophyllotoxin series derivates and application thereof.
Two, background technology:
Nuisanceless Pesticide Research Service Center, Xibei Agroforestry Science and T, found the biological activity of sandy ground cypress first in nineteen ninety, and sandy ground cypress insecticidal activity carried out systematic study research, on the basis of this research, applied for " " Shadibai " pesticide and manufacture method thereof ", and license, the patent No.: ZL94105885.9 have been obtained.
By further research to sandy ground cypress insecticide active substance, therefrom isolated three kinds of monomeric compounds, the structure assay certificate, these three kinds of compounds are respectively podophyllotoxin, deoxidation podophyllotoxin and β-podophyllotoxin, its structural formula as shown in the figure:
Podophyllotoxin deoxidation podophyllotoxin
Figure A20031010587000041
β-podophyllotoxin
Carried out further research by structure and activity relationship to podophyllotoxin, podophyllotoxin is modified synthetic gained analogue, carry out biological assay, getting its structure with active pass is: the structure that guarantees the trans lactonic ring that C-2, C-3 position are connected, 4 ' is methoxyl group, and 4 is very strong decorating site.Based on this, modify 4 with different substituting groups, synthesized a series of malicious mortar toxin derivant, and done the biological assay of system with small cabbage moth, mythimna separata, cabbage caterpillar, apply for and obtained patent of invention " podophyllum kind compound of tool insecticidal activity ", patent No. ZL02114480.X on this basis.
Three, summary of the invention:
The present invention is on the basis of the podophyllum kind compound of tool insecticidal activity, synthesized a series of podophyllotoxin analogue, and the biological activity of each compound carried out the mensuration of system, the molecular structure and the application aspect various agricultural insects such as control small cabbage moth, mythimna separata, cabbage caterpillar thereof of podophyllotoxin series derivates are provided.
For achieving the above object, the technical solution used in the present invention is:
A kind of podophyllotoxin series derivates, its special character is: its chemical general formula is:
Wherein sterie configuration is: C-1, α configuration;
Figure A20031010587000052
Between be connected to trans lactonic ring,
The C-4 position be configured as the β position.
Wherein the C-4 bit substituent can be:
(1)
Figure A20031010587000061
Be compound 1, i.e. acetyl table Podophyllum emodi var chinense;
(2) Be compound 2, i.e. propionyl table Podophyllum emodi var chinense;
(3) R=-SH is compound 3, i.e. sulfydryl table Podophyllum emodi var chinense;
(4) R=-SCH 3, be compound 4, i.e. first sulfydryl table Podophyllum emodi var chinense;
(5) R=-SCH 2CH 3, be compound 5, i.e. second sulfydryl table Podophyllum emodi var chinense;
(6)
Figure A20031010587000063
Be compound 6, i.e. thioacetyl table Podophyllum emodi var chinense ester;
(7)
Figure A20031010587000064
Be compound 7, i.e. nicotinic acid table Podophyllum emodi var chinense ester;
(8)
Figure A20031010587000065
Be compound 8, i.e. Yi Yansuan table Podophyllum emodi var chinense ester;
(9) R=-NH 2, be compound 9, promptly amino table Podophyllum emodi var chinense;
(10) R=-N 3, being compound 10, nitrogen table Podophyllum emodi var chinense promptly changes;
(11) R=-NH-C 3H 7, be compound 11, i.e. n-propylamine base table Podophyllum emodi var chinense;
(12) R=-NH-C 4H 9Be compound 12, i.e. n-butyl amine base table Podophyllum emodi var chinense;
(13) R=-SCH 2CH 2CH 3Be compound 13, i.e. n-propyl table Podophyllum emodi var chinense thioether;
(14) R=-OCH 3Be compound 14, i.e. β-methyl ether table Podophyllum emodi var chinense.
A kind of application of podophyllotoxin series derivates, its special character is: described podophyllotoxin series compound thing can be used for preventing and treating various agricultural insects such as small cabbage moth, mythimna separata, cabbage caterpillar.
The present invention has further inquired into podophyllotoxin derivative structure and active relation, on the basis of patent " podophyllum kind compound of tool insecticidal activity ", synthesized a series of podophyllotoxin analogue, make the podophyllotoxin series products form series, and the biological activity of each compound carried out the mensuration of system, this research has constituted main contents of the present invention.The podophyllotoxin series compound can be used for preventing and treating various agricultural insects such as small cabbage moth, mythimna separata, cabbage caterpillar, and effect significantly is public nuisance-free agricultural chemicals, has vast market prospect.
Four, description of drawings:
Fig. 1, Fig. 2, Fig. 3 are respectively m/z, 1HNMR and the infared spectrum of compound 1;
Fig. 4, Fig. 5, Fig. 6 are respectively m/z, 1HNMR and the infared spectrum of compound 2;
Fig. 7, Fig. 8, Fig. 9 are respectively m/z, 1HNMR and the infared spectrum of compound 3;
Figure 10, Figure 11, Figure 12 are respectively m/z, 1HNMR and the infared spectrum of compound 4;
Figure 13, Figure 14, Figure 15 are respectively m/z, 1HNMR and the infared spectrum of compound 5;
Figure 16, Figure 17, Figure 18 are respectively m/z, 1HNMR and the infared spectrum of compound 6;
Figure 19, Figure 20, Figure 21 are respectively m/z, 1HNMR and the infared spectrum of compound 7;
Figure 22, Figure 23, Figure 24 are respectively m/z, 1HNMR and the infared spectrum of compound 8;
Figure 25, Figure 26, Figure 27 are respectively m/z, 1HNMR and the infared spectrum of compound 9;
Figure 28, Figure 29, Figure 30 are respectively m/z, 1HNMR and the infared spectrum of compound 10;
Figure 31, Figure 32, Figure 33 are respectively m/z, 1HNMR and the infared spectrum of compound 11;
Figure 34, Figure 35, Figure 36 are respectively m/z, 1HNMR and the infared spectrum of compound 12;
Figure 37, Figure 38, Figure 39 are respectively m/z, 1HNMR and the infared spectrum of compound 13;
Figure 40, Figure 41, Figure 42 are respectively m/z, 1HNMR and the infared spectrum of compound 14.
Five, embodiment:
The site that the present invention modifies podophyllotoxin is as follows:
When R substituting group difference, get
Figure A20031010587000071
The sterie configuration difference in generation has formed different podophyllotoxin analogues.
Below in conjunction with the m/z of each compound, 1HNMR and infared spectrum are elaborated to the structure of each compound of the present invention:
Compound 1 acetyl table Podophyllum emodi var chinense ester
Accompanying drawing 1,2,3 is respectively m/z, 1HNMR and the infared spectrum of compound 1
m.p.156~158℃
MS.(EI)m/z(Int％)456(M +，16)；397(M-CH 3-(C＝O)-O，24)
1HNMR. (CDCl 3). δ ppm:2.18 (3H, ethanoyl CH 3); (2.90 2H, 2.3 2 H);
3.76(6H，S，3′.5′OCH 3)；3.80(3H，S，4′OCH 3)；
(4.20 1H, 11 H); (4.38 2H, 1 and 11 ' position H);
4.61 (1H, d, J=4.2H 24 H); 5.98 (2H, O-CH 2-O);
(6.59 2H, 2 ' 6 ' position H); (6.54 1H, 8 H); (6.77 1H, 5 H)
IR (KBr. γ max) cm -1, 1779 (lactone=C=O); 1727 (acetonyl ester=C=O); 1626,1584,1506,1462 (skeletal vibrations of aromatic ring);
1212,1125 (the C-O-C stretching vibrations of ester);
941(O-CH 2-O)
Compound 2 propionyl table Podophyllum emodi var chinense esters
Accompanying drawing 4,5,6 is respectively m/z, 1HNMR and the infared spectrum of compound 2
m.p.?142~144℃
MS.(EI)m/z(Int％)470(M +，82)；455(M-CH 3，3)
397(M-CH 3-CH 2-(C＝O)-O，18)
1HNMR. (CDCl 3). δ ppm:1.21 (3H, propionyl CH 3);
1.95 (2H connects on the propionyl=CH of C=O 2);
2.84,2.90 (2H, two H of prosposition);
3.76(6H，3′，5′-OCH 3)；3.81(3H，4′-OCH 3)；
(4.21 1H, 11 H); (4.60 1H, 1 H);
(4.78 1H, m, 11 ' position H); (5.00 1H, 4 H); 5.99 (2H, O-CH 2-O);
(6.39 2H, 2 ' 6 ' position H); (6.54 1H, 8 H); (6.76 1H, 5 H)
IR (KBr. γ max) cm -1, 1774 (lactone=C=O); 1737 (the propionyl ester=C=O);
1626,1583,1506,1485 (skeletal vibrations of aromatic ring);
1240,1125 (the C-O-C stretching vibrations of ester);
934(O-CH 2-O)
Compound 3 sulfydryl table Podophyllum emodi var chinense
Accompanying drawing 7,8,9 is respectively m/z, 1HNMR and the infared spectrum of compound 3
m.p.98~100℃
MS.(EI)m/z(Int％)430(M +，100)；397(M-HS，64)
1HNMR. (CDCl 3). δ ppm.2.51 (1H, 3 H); (2.86 1H, 2 H);
3.73(6H，S，3′.5′-OCH 3)；3.78(3H，4′-OCH 3)；
(4.21 1H, 11 H); (4.40 1H, 1 H); (4.42 1H, 11 ' position H);
(4.59 1H, 4 H); 5.98 (2H, ocH 2-o); (6.27 2H, 2 ' 6 ' position H); (6.46 1H, 8 H); (6.93 1H, 5 H)
IR (KBr. γ max) cm -1, 2580 (S-H, weak); 1776 (Vic-O lactones);
1583,1506,1480 (skeletal vibrations of aromatic ring);
1236,1126 (the C-O-C stretching vibrations of ester), 668 (S-C)
Compound 4 methylthio group table Podophyllum emodi var chinense ethers
Accompanying drawing 10,11,12 is respectively m/z, 1HNMR and the infared spectrum of compound 4
m.p.220~222℃
MS.(EI)m/z(Int％)m/z?444(M +，100)；397(M-SCH 3，100)
1HNMR. (CDCl 3). (3H is connected with the CH of sulphur to δ ppm:2.16 3); (3.18 1H, m.3 position H);
(3.28 1H, dd, 2 H); 3.74 (6H, S 13 ' 5 ' OCH 3);
3.79 (3H, S, 4 ' OCH 3); (4.15 1H, d, 11 H);
(4.39 1H, S, 1 H); (4.41 14, d, 11 ' position H);
4.54 (1H, d, J=4.8H 2, 4 H); 5.94 (2H, dd, O-CH 2-O);
(6.28 2H, S, 2 ' 6 ' position H); (6.43 1H, S, 8 H); (6.94 1H, S, 5 H)
IR (KBr. γ max) cm -1, 1771 (lactone=C=O); 1589,1506,1482 (skeletal vibrations of aromatic ring);
1328 (S-CH 3Flexural vibration); 1234,1124 (C-O-C stretching vibrations)
934(O-CH 3-O)
Compound 5 ethylmercapto group table Podophyllum emodi var chinense ethers
Accompanying drawing 13,14,15 is respectively m/z, 1HNMR and the infared spectrum of compound 5
m.p.138~140℃
MS.(EI)m/z(Int％)458(M +，100)；397(M-SC 2H 5，98)
1HNMR. (CDCl 3). δ ppm:1.25 (3H, t, SC 2H 3In CH 3);
2.53 (2H, q, SC 2H 3In CH 2); (2.83 1H, m, 3 H);
(3.25 1H, dd, 2 H); 3.74 (6H, S, 3 ' .5 '-OCH 3);
3.80 (3H, S, 4 ' OCH 3); (4.02 1H, t, 11 H);
(4.38 1H, d, 1 H); (4.41 14, m, 11 ' position H);
4.54(1H，d，J＝5.1H 2)；5.99(2H，O-CH 2-O)；
(6.37 2H, 2 ' .6 ' position H); (6.42 1H, 8 H);
(6.92 1H, 5 H)
IR (KBr. γ max) cm -1, 1776 (lactone=C=O);
1587,1506,1481,1457 (skeletal vibrations of aromatic ring);
1419,1328 (S-CH 2-CH 3Flexural vibration);
1236,1126 (the C-O-C stretching vibrations of ester)
936(O-CH 2-O)
Compound 6 thio-ethyl table Podophyllum emodi var chinense esters
Accompanying drawing 16,17,18 is respectively m/z, 1HNMR and the infared spectrum of compound 6
m.p.188~190℃
MS.(EI)m/z(Int％)472(M +，66)；429(M-CH 3-C＝O)；
397(M-CH 3-C(＝O)-S，65)
1HNMR. (CDCl 3). δ ppm:2.43 (3H, S, CH 3-C (=O)-CH on the S 3)
(2.95 1H, dd, 2 H);
(3.22 1H, m, 3 H); 3.77 (6H, S, 3 ' .5 ' position OCH 3);
3.83 (3H, S, 4 ' position OCH 3); (4.38 1H, t, 11 H);
(4.56 d, 1H, 1 H); 5.03 (1H, d, J=4.8H 2, 4 H);
5.99 (2H, d, O-CH 2-O); (6.29 2H, S, 2 ' .6 ' position H);
(6.45 1H, S, 8 H); (6.78 1H, S, 5 H)
IR. (KBr. γ max) cm -1, 1777 (lactone=C=O); 1690 (ethanoyl=C=O);
1588,1506,1482,1456 (aromatic ring frame vibrations);
1235,1129 (the C-O-C stretching vibrations of ester)
934 (O-CH 2-O); 628 (S-C flexural vibration);
Compound 7 nicotinic acid table Podophyllum emodi var chinense esters
Accompanying drawing 19,20,21 is respectively m/z, 1HNMR and the infared spectrum of compound 7
m.p.177~178℃
MS.(EI)m/z(Int％)519(M +，66)；504(M-CH 3，3)；
442(M-O，10)；397(M-CH 3-C(＝O)-O，12)
1HNMR. (DMSO-d 6). δ ppm:2.95 (1H, m, 3 H); (3.15 1H, dd, 2 H);
3.42 (6H, S, 3 ' .5 ' position OCH 3); 3.47 (3H, S, 4 ' OCH 3);
(4.11 1H, t, 11 H); (4.56 1H, d, 1 H); (4.39 1H, m, 11 ' position H)
4.61 (1H, d, J=5.7H 2, 4 H); 5.97 (2H, O-CH 2-O);
(6.35 2H, 2 ' .6 ' position H); (6.46 1H, S, 8 H);
(6.64 1H, S, 5 H); 7.59 (1H, pyridine ring 5 " H of position);
8.31 (1H, pyridine ring 6 " H of position); 8.82 (1H, pyridine ring 4 " position H);
9.08 (1H, pyridine ring 2 " H of position)
IR. (KBr. γ max) cm -1: 1776 (lactone=C=O); 1723 (nicotinic acid=C=O);
1590,1506,1483 (aromatic ring frame vibrations);
1238,1126 (the C-O-C stretching vibrations of ester)
929(O-CH 2-O)
Compound 8 Yi Yansuan table Podophyllum emodi var chinense esters
Accompanying drawing 22,23,24 is respectively m/z, 1HNMR and the infared spectrum of compound 8
m.p.172-174℃
MS.(EI)m/z(Int％)519(M +，19)；396(M -，3)
1HNMR. (. (DMSO-d 6)). δ ppm:2.91 (1H, m, 3 H);
(3.44 1H, dd, 2 H);
3.60(6H，S，3′.5′OCH 3)；3.65(3H，S，4′OCH 3)；
(4.29 2H, t, 11,11 ' position H); (4.42 1H, t, 1 H);
4.60 (1H, d, J=4.2H 2, 4 H); 6.02 (2H, O-CH 2-O);
(6.38 2H, d, 2 ' .6 ' position H); (6.64 1H, 8 H);
(7.09 1H, 5 H); (7.81 2H, the 2H of pyridine ring 2 ' .6 ' position);
(8.79 2H, the 2H of pyridine ring 3 ' .5 ' position)
IR. (KBr. γ max) cm -1: 1778 (lactone=C=O); 1727 (pyridine ring 3 ' .5 '=C=O);
1589,1506,1484 (skeletal vibrations of aromatic ring);
1239,1125 (the C-O-C stretching vibrations of ester)
928(O-CH 2-O)
Compound 9 amino table Podophyllum emodi var chinense
Accompanying drawing 25,26,27 is respectively m/z, 1HNMR and the infared spectrum of compound 9
m.p.156~157℃
MS.(EI)m/z(Int％)413(M +，100)；396(M-NH 3，13)
1HNMR. (CDCl 3). δ ppm:2.17 (2H, S, NH 2On H); (2.98 1H, m, the H on 3); (3.30 1H, dd, 2 H); 3.76 (6H, S, 3 ' .5 ' position OCH 3);
3.81 (3H, S, 4 ' position OCH 3); (4.18 1H, m, 11 H);
(4.31 1H, d, 11 ' position H); (4.66 1H, d, 1 H);
(4.79 1H, d, J=3.9H2,4 H); 6.00 (2H, d, O-CH 2-O);
6.36 (2H, 2 ' .6 ' is H); (6.53 1H, 8 H);
(6.81 1H, 5 H);
IR. (KBr. γ max) cm -1: 3592 (NH 2); 1770 (lactone=C=O);
1586,1507,1483 (skeletal vibrations of aromatic ring);
1239,1127 (the C-O-C stretching vibrations of ester)
939(O-CH 2-O)
Compound 10 is nitrogen table Podophyllum emodi var chinense repeatedly
Accompanying drawing 28,29,30 is respectively m/z, 1HNMR and the infared spectrum of compound 10
m.p.180~182℃
MS.(EI)m/z(Int％)439(M +，100)；425(M-N，6)；
425(M-N 2，18)；
397(M-N 3，24)
1HNMR (CDCl 3). δ ppm:2.92 (1H, m, 3 H); (3.15 1H, dd, 2 H);
3.76 (6H, S, 3 ' .5 ' position OCH 3); 3.80 (3H, S, 4 ' OCH 3);
4.30 (2H, d, 11,11 ' 2H); (4.63 1H, 1 H);
4.77 (1H, d, J=3.6H 2, 4 H); 6.01 (2H, O-CH 2-O);
(6.59 1H, S, 8 H); (6.80 1H, 5 H);
IR. (KBr. γ max) cm -1: 2103 (N 3Stretching vibration); 1768 (lactone=C=O);
1589,1501,1487 (skeletal vibrations of aromatic ring);
1237,1127 (the C-O-C stretching vibrations of ester)
932(O-CH 2-O)
Compound 11 n-propylamine base table Podophyllum emodi var chinense
Accompanying drawing 31,32,33 is respectively m/z, 1HNMR and the infared spectrum of compound 11
m.p.142~144℃
MS.(EI)m/z(Int％)455(M +，22)；396(M-C 3H 7NH 2，100)；
381(M-C 3H 7NH 2-CH 3，17)
1HNMR (CDCl 3). δ ppm:0.85 (3H, the third amino CH that goes up 3);
0.94 (2H is connected with CH on third amino 3CH 2);
2.03 (2H is connected with the CH of N atom on third amino 2);
2.16 (1H, S, NH); (3.59 1H, m, 3 H); (3.60 1H, dd, 2 H);
3.75(6H，S，3′.5′OCH 3)；3.79(3H，S，4′OCH 3)；
(4.33 1H, m, 11 H); (4.52 1H, dd, 11 ' position H);
(4.70 1H, 1 H); (4.86 1H, 4 H); 5.96 (2H, O-CH 2-O);
6.37 (2H, 2 ' .6 ' is H); (6.62 1H, 8 H); (6.71 1H, 5 H)
IR. (KBr. γ max) cm -1: 3484 (NH stretching vibrations); 1756 (lactone=C=O);
1589,1506,1484,1462 (skeletal vibrations of aromatic ring);
1232,1126 (the C-O-C stretching vibrations of ester);
932(O-CH 2-O)
Compound 12 n-Butyl Amine 99 base table Podophyllum emodi var chinense
Accompanying drawing 34,35,36 is respectively m/z, 1HNMR and the infared spectrum of compound 12
m.p.184~186℃
MS.(EI)m/z(Int％)469(M +，2)；428(M-C 3H 5，100)；
413(M-C 4H 8，4)；
396(M-C 4H 9NH 2，29)；381(M-C 4H 9NH 2-CH 3，6)
1HNMR (CDCl 3). δ ppm:0.90 (3H, t, CH on the butylamine 3);
1.25 (4H, m are connected with CH on the butylamine base 3Two CH 2);
2.05 (1H, NH); 2.16 (2H, the CH that links to each other with the N atom on the butylamine 2);
(2.85 1H, m, 3 H); (3.28 1H, dd, 2 H);
3.73 (6H, S, two OCH of 3 ' .5 ' 3); 3.79 (3H, S, 4 ' position OCH 3);
(4.33 1H, m, 11.11 ' position H); (4.61 1H, d, 1 H);
(4.86 1H, hump, 4 H); 5.97 (2H, d, O-CH 2-O);
(6.27 2H, S, 2 ' .6 ' position H); (6.55 1H, S, 8 H);
(6.88 1H, S, 5 H)
IR. (KBr. γ max) cm -1: 3456 (NH); 1773 (lactone=C=O);
1589,1506,1484 (skeletal vibrations of aromatic ring);
1234,1125 (the C-O-C stretching vibrations of ester);
932(O-CH 2-O)
Compound 13 n-propyl table Podophyllum emodi var chinense thioethers
Accompanying drawing 37,38,39 is respectively m/z, 1HNMR and the infared spectrum of compound 13
m.p.184~186℃
MS.(EI)m/z(Int％)472(M +，53)；429(M-C 3H 7，1.5)；
397(M-SC 3H 7，83)
1HNMR (CDCl 3). δ ppm:1.05 (3H, t, n-propyl CH 3);
1.71 (2H, m are connected with CH on the n-propyl 3CH 2);
2.51 (2H, m are connected with the CH of S on the n-propyl 2);
(3.13 1H, m, 3 H); (3.25 1H, dd, 2 H);
3.74(6H，S，3′.5′OCH 3)；3.78(3H，S，4′OCH 3)；
(4.17 1H, dd, 11 H); (4.39 1H, d, 1 H);
(4.41 1H, S, 11 ' position H); 4.54 (1H, d, J=5.1H 2, 4 H)
5.95 (2H, d, O-CH 2-O); (6.28 2H, S, 2 ' .6 ' position H);
(6.43 1H, S, 8 H); (6.93 1H, d, 5 H)
IR. (KBr. γ max) cm -1: 3456 (NH); 1773 (lactone=C=O);
1585,1506,1482 (skeletal vibrations of aromatic ring);
1238,1127 (the C-O-C stretching vibrations of ester);
938(O-CH 2-O)；766(S-C)
Compound 14 β-methyl ether table Podophyllum emodi var chinense
Accompanying drawing 40,41,42 is respectively m/z, 1HNMR and the infared spectrum of compound 14
m.p.175~176℃
MS.(EI)m/z(Int％)428(M +，57)；410(M-H 2O，12)；
396(M-HOCH 3，40)
1HNMR (CDCl 3). δ ppm:2.88 (1H, m, 3 H); (3.39 1H, dd, 2 H);
3.47 (3H, S, OCH on the methyl ether 3); 3.73 (6H, S, 3 ' .5 ' OCH 3);
3.80 (3H, S, 4 '-OCH 3); (4.30 1H, d, 11 H);
(4.33 1H, d, 11 ' position H); (4.36 1H, d, 1 H);
(4.61 1H, d, J=6H2,4 H); 5.98 (2H, d, O-CH 2-O);
(6.25 2H, S, 2 ' .6 ' position H); (6.56 1H, S, 8 H);
(6.82 1H, S, 5 H)
IR. (KBr. γ max) cm -1: 2827 (OCH 3); 1767 (ester=C=O);
1587,1507,1485 (skeletal vibrations of aromatic ring);
1234-1129 (the C-O-C stretching vibration of ester);
934(O-CH 2-O)
Below the Toxicity Determination of mythimna separata, small cabbage moth, cabbage caterpillar is further specified the activity of each compound by each compound
Experimental example 1:
One, content of the test: 14 podophyllotoxin derivatives are to the biological activity of mythimna separata
Two, test materials and method
1 material
(1) instrument: culture dish (7.5cm) * 72, filter paper, dropper, scissors, penicillin bottle (6ml) * 24, thieving paper, transfer pipet (2mL, 10mL) rubber pipette bulb, plastic culture dish * 20, take the photograph son, electronic balance (being accurate to 0.1mg)
(2) reagent: acetone, podophyllotoxin derivative: 14 podophyllotoxin derivatives, sandy ground cypress seed extracting solution ethanol extract
(3) examination worm: mythimna separata (Mythimna separata Walker), provide by " Nuisanceless Pesticide Research Service Center, Xibei Agroforestry Science and T " insectary, individual 3 instar larvaes of the same size of picking supply examination after hungry 2-3 hour
2 methods
Adopt leaflet dish additive process
Three, operation steps
At diameter is glass culture dish bottom shop one deck filter paper of 7.5cm, adds water and preserves moisture, and each culture dish is put 53 mythimna separatas in age (hungry 2 hours), and three repetitions are established in each processing, i.e. totally 15 mythimna separatas.With acetone diluted sample is become finite concentration (4mg/mL), do the medicament contrast with podophyllotoxin and sandy ground cypress seed extracting solution ethanol extract respectively, acetone compares, and clear water is made blank.Make the leaf dish of 1cm with punch tool, in soup, soak 1-2 second, put into culture dish after drying naturally, cover at ware and repave one deck filter paper, and add water and preserve moisture, in case the examination worm runs away.Room temperature (T=25 ± 2 ℃; R.H.=65-80%) raise down.Worm to be tried eats up maize leaf, adds corresponding maize leaf again, looks the examination worm night and gets the food situation, can add several.Write down 12 hours, 24 hours, 48 hours and 72 hours examination worm respectively and get food maize leaf number, calculate 12 hours, 24 hours, 48 hours and food refusal rate and 72 hours mortality ratio of 72 hours of 4mg/mL according to following formula.
Figure A20031010587000191
Four, result and analysis:
Table 1 podophyllotoxin derivative is to the biological activity of mythimna separata
Compound 12 hours 24 hours
Numbering Food ingestion The survival borer population Average food ingestion Proofread and correct the food refusal rate Food ingestion The survival borer population Average food ingestion Proofread and correct food refusal rate %
Compound
1 ??1 ??0.35 5 0.1133 88.59 ??0.25 5 0.0293 91.79
??2 ??0.52 5 ??0.18 5
??3 ??0.83 5 ??0.01 5
Compound 2 ??1 ????1.37 ????5 ?0.2840 ????71.41 ????1.3 ????5 ??0.1433 ??75.39
??2 ????1.67 ????5 ????0.85 ????5
??3 ????1.22 ????5 ????0 ????5
Compound 3 ??1 ????0.25 ????5 ?0.0991 ????90.02 ????0 ????5 ??0.0000 ??94.29
??2 ????0.82 ????1 ????0 ????1
??3 ????0.02 ????5 ????0 ????5
Compound 4 ??1 ????0.7 ????5 ?0.1327 ????86.64 ????0.85 ????5 ??0.1120 ??85.91
??2 ????0.7 ????5 ????0.48 ????5
??3 ????0.59 ????5 ????0.35 ????5
Compound 5 ??1 ????0.01 ????5 ?0.0340 ????96.58 ????0 ????5 ??0.0136 ??97.26
??2 ????0.31 ????5 ????0 ????1
??3 ????0.19 ????5 ????0.15 ????5
Compound 6 ??1 ????2.48 ????5 ?0.2807 ????71.74 ????0.15 ????5 ??0.0287 ??82.19
??2 ????0.88 ????5 ????0 ????5
??3 ????0.85 ????5 ????0.28 ????5
Compound 7 ??1 ????0.4 ????5 ?0.1950 ????80.37 ????0.02 ????5 ??0.0547 ??85.62
??2 ????1.23 ????4 ????0.52 ????5
??3 ????1.1 ????5 ????0.28 ????5
Compound 8 ??1 ????1.85 ????5 ?0.4986 ????49.81 ????0.58 ????5 ??0.0829 ??66.52
??2 ????3.72 ????5 ????0.4 ????5
??3 ????1.41 ????4 ????0.18 ????4
Compound 9 ??1 ????2.15 ????5 ?0.4067 ????59.06 ????0.95 ????5 ??0.2167 ??64.11
??2 ????1.99 ????5 ????1.42 ????5
??3 ????1.96 ????5 ????0.88 ????5
Compound 10 ??1 ????0.75 ????5 ?0.1400 ????85.91 ????0.47 ????5 ??0.0447 ??89.37
??2 ????0.76 ????5 ????0.05 ????5
??3 ????0.59 ????5 ????0.15 ????5
Compound 11 ??1 ????0.05 ????5 ?0.0036 ????99.64 ????0 ????5 ??0.0017 ??99.70
??2 ????0 ????4 ????0.02 ????4
??3 ????0 ????5 ????0 ????3
Compound 12 ??1 ????0.16 ????5 ?0.0747 ????92.48 ????0 ????5 ??0.0100 ??95.12
??2 ????0.4 ????5 ????0 ????5
??3 ????0.56 ????5 ????0.15 ????5
Compound 13 ??1 ????1.4 ????5 ?0.2200 ????77.85 ????0 ????5 ??0.0680 ??83.42
??2 ????1.22 ????5 ????0.8 ????5
??3 ????0.68 ????5 ????0.22 ????5
Compound 14 ??1 ????2.45 ????5 ?0.4713 ????52.55 ????2.95 ????5 ??0.5800 ??39.46
??2 ????3.53 ????5 ????2.6 ????5
??3 ????1.09 ????5 ????3.15 ????5
Podophyllotoxin ??1 ????0.9 ????5 ?0.1833 ????81.54 ????0.21 ????5 ??0.0420 ??87.03
??2 ????1 ????5 ????0 ????5
??3 ????0.85 ????5 ????0.42 ????5
Sandy ground cypress seed medicinal extract ethanol extract ??1 ????1.4 ????4 ?0.2057 ????79.29 ????0.17 ????4 ??0.1036 ??82.19
??2 ????1.08 ????5 ????0.65 ????5
??3 ????0.5 ????5 ????0.63 ????5
Acetone ??1 ????5 ????5 ?0.9933 ????4 ????5 ??0.7433
??2 ????5 ????5 ????2.3 ????5
????3 ????4.9 ????5 ????4.85 ????5
The clear water contrast ????1 ????5 ????5 ?0.8333 ????2.56 ????5 ??0.3820
????2 ????4.5 ????5 ????1.85 ????5
????3 ????3 ????5 ????1.32 ????5
Continuous table 1
Compound 48 hours 72 hours
Numbering Food ingestion The survival borer population Average food ingestion Proofread and correct food refusal rate % Food ingestion The survival borer population Dead borer population Mortality ratio % Average food ingestion Proofread and correct food refusal rate % Average mortality % Corrected mortality %
Compound 1 ??1 ?0.05 ??5 ?0.0075 ?94.24 ?0 ??3 ??2 ?40.00 ?0.0357 ?96.21 ?53.33 ?53.33
??2 ?0.04 ??3 ?0.25 ??2 ??3 ?60.00
??3 ?0 ??4 ?0 ??2 ??3 ?60.00
Compound 2 ??1 ?0.04 ??5 ?0.0027 ?83.50 ?0.55 ??5 ??0 ?0.0000 ?0.0591 ?90.01 ?26.67 ?26.67
??2 ?0 ??5 ?0.1 ??3 ??2 ?40.00
??3 ?0 ??5 ?0 ??3 ??2 ?40.00
Compound 3 ??1 ?0 ??4 ?0.0000 ?96.20 ?0 ??3 ??1 ?25.00 ?0.0000 ?97.98 ?8.33 ?8.33
??2 ?0 ??1 ?0 ??1 ??0 ?0.0000
??3 ?0 ??5 ?0 ??5 ??0 ?0.0000
Compound 4 ??1 ?0.14 ??5 ?0.0436 ?88.94 ?0.49 ??4 ??1 ?20.00 ?0.1356 ?91.35 ?40.00 ?40.00
??2 ?0 ??4 ?0 ??1 ??4 ?80.00
??3 ?0.47 ??5 ?0.73 ??4 ??1 ?20.00
Compound 5 ??1 ?0 ??4 ?0.0000 ?98.17 ?0 ??2 ??3 ?60.00 ?0.0000 ?99.03 ?66.67 ?66.67
??2 ?0 ??4 ?0 ??1 ??4 ?80.00
??3 ?0 ??4 ?0 ??2 ??3 ?60.00
Compound 6 ??1 ?0 ??4 ?0.0000 ?88.13 ?0.01 ??2 ??2 ?50.00 ?0.0025 ?93.63 ?70.00 ?70.00
??2 ?0 ??5 ?0 ??1 ??4 ?80.00
??3 ?0 ??5 ?0 ??1 ??4 ?80.00
Compound 7 ??1 ?0 ??5 ?0.0115 ?89.98 ?0.03 ??5 ??0 ?0.0000 ?0.0633 ?93.37 ?8.33 ?8.33
??2 ?0 ??4 ?0.01 ??3 ??1 ?25.00
??3 ?0.15 ??4 ?0.72 ??4 ??0 ?0.0000
Compound 8 ??1 ?0 ??5 ?0.0946 ?74.06 ?1 ??4 ??1 ?20.00 ?0.1625 ?82.88 ?20.00 ?20.00
??2 ?0.88 ??4 ?0.3 ??4 ??1 ?20.00
??3 ?0.35 ??4 ?0.65 ??4 ??1 ?20.00
Compound 9 ??1 ?1.13 ??5 ?0.3393 ?63.06 ?1.38 ??5 ??0 ?0.0000 ?0.3843 ?0.7250 ?0.0667 ?0.0667
??2 ?1.98 ??5 ?2.2 ??5 ??0 ?0.0000
??3 ?1.98 ??5 ?1.8 ??4 ??1 ?20.00
Compound 10 ??1 ?0.88 ??5 ?0.0643 ?90.45 ?1.7 ??5 ??0 ?0.0000 ?0.2750 ?89.30 ?20.00 ?20.00
??2 ?0.01 ??5 ?1.1 ??5 ??0 ?0.0000
??3 ?0.01 ??4 ?0.5 ??2 ??3 ?60.00
Compound 11 ??1 ?0 ??5 ?0.0000 ?99.80 ?0 ??1 ??4 ?80.00 ?0.0000 ?99.89 ?82.22 ?82.22
??2 ?0 ??4 ?0 ??0 ??4 ?100.00
??3 ?0 ??1 ?0 ??1 ??2 ?66.67
Compound 12 ??1 ?0.75 ??5 ?0.0780 ?93.76 ?0.65 ??5 ??0 ?0.0000 ?0.0664 ?95.32 ?6.67 ?6.67
??2 ?0.42 ??5 ?0.18 ??5 ??0 ?0.0000
??3 ?0 ??5 ?0.1 ??4 ??1 ?20.00
Compound 13 ????1 ?0 ????5 ?0.0233 ?88.05 ??0.2 ????5 ????0 ?0.0000 ?0.0467 ?92.69 ?0.0000 ?0.0000
????2 ?0.33 ????5 ??0.5 ????5 ????0 ?0.0000
????3 ?0.02 ????5 ??0 ????5 ????0 ?0.0000
Compound 14 ????1 ?0.1 ????5 ?0.0514 ?57.68 ??2 ????4 ????1 ?20.00 ?0.3625 ?70.09 ?13.33 ?13.33
????2 ?0.33 ????5 ??0.6 ????4 ????1 ?20.00
????3 ?0.29 ????4 ??1.75 ????4 ????0 ?0.0000
Podophyllotoxin ????1 ?0.35 ????5 ?0.0379 ?89.90 ??1 ????5 ????0 ?0.0000 ?0.1227 ?0.9212 ?21.67 ?21.67
????2 ?0.18 ????4 ??0.1 ????3 ????1 ?25.00
????3 ?0 ????5 ??0.25 ????3 ????2 ?40.00
Sandy ground cypress seed medicinal extract ethanol extract ????1 ?0.7 ????4 ?0.1500 ?82.38 ??2.2 ????4 ????0 ?0.0000 ?0.3786 ?82.89 ?0.0000 ?0.0000
????2 ?0.8 ????5 ??2.1 ????5 ????0 ?0.0000
????3 ?0.6 ????5 ??1 ????5 ????0 ?0.0000
Acetone ????1 ?2.6 ????5 ?0.8692 ??10 ????5 ????0 ?0.0000 ?2.2923
????2 ?4.5 ????5 ??9.8 ????5 ????0 ?0.0000
????3 ?4.2 ????3 ??10 ????3 ????0 ?0.0000
The clear water contrast ????1 ?4.5 ????5 ?0.6500 ??6 ????5 ????0 ?0.0000 ?1.8429
????2 ?5 ????5 ??10 ????4 ????0 ?0.0000
????3 ?0.25 ????5 ??9.8 ????5 ????0 ?0.0000
By in the table as can be seen, 20 podophyllotoxin derivatives of synthetic all have in various degree antifeedant activity to mythimna separata, along with the prolongation of time, antifeedant activity also constantly strengthens.Wherein, the antifeedant activity of derivative 9 is the highest, and 2,3,5,7,15,16,19 antifeedant activity all is higher than podophyllotoxin, and 3,9,10,15 also have stronger cytotoxicity.
EXPERIMENTAL EXAMPLE 2:
14 podophyllotoxin derivatives are to the biological activity of small cabbage moth
To the small cabbage moth activity determination method:
Select polypide of the same size three age small cabbage moth for the examination worm.With acetone diluted sample is become finite concentration (2mg/mL), compare with acetone, clear water is made blank.。Cabbage leaves is cut into the small pieces of about 2cm2, in institute's vehicle, floods 3～5S, treat that solvent evaporates does the back with its examination worm of feeding, with the clear water is contrast, three repetitions are established in every processing, and 10 examinations of every re-treatment worm is cultivated in the culturing room of examination worm about 25 ℃ that handles well.Every 24h checks a death condition, and feeds with the fresh medicine blade that soaks, and 72h checks total death condition, obtains according to the contrast mortality ratio and respectively handles corrected mortality.Test-results sees Table 2.
14 podophyllotoxin derivatives of table 2 are to small cabbage moth determination of activity result
Compound Small cabbage moth Plutella xylostella
Mortality ratio %mortality
????1d ????3d
Compound
1 ????53.3 ????67.8
Compound 2 ????46.2 ????51.3
Compound 3 ????20.0 ????20.0
Compound 4 ????50.0 ????70.0
Compound 5 ????78.7 ????83.3
Compound 6 ????81.3 ????90.7
Compound 7 ????17.3 ????27.7
Compound 8 ????33.3 ????33.3
Compound 9 ????66.7 ????86.7
Compound 10 ????16.7 ????26.7
Compound 11 ????93.3 ????100.0
Compound 12 ????16.7 ????16.7
Compound 13 ????33.3 ????53.3
Compound 14 ????83.3 ????93.3
Acetone ????0.0 ????0.0
Clear water ????0.0 ????0.0
EXPERIMENTAL EXAMPLE 3
14 podophyllotoxin derivatives are to the biological activity of cabbage caterpillar
To the cabbage caterpillar activity determination method:
Adopt leaflet dish additive process:, and add water and preserve moisture at the shop, culture dish bottom of diameter 5cm one deck filter paper.Select the larva in early stage in 5 ages of big or small consistent stalwartness, hungry 2h, put one in every ware, each compound is become the concentration of 1mg/ml with acetone diluted; With punch tool fresh cabbage leaves is made the leaf dish of 1cm, in the soup for preparing, soak 1-2s, dry naturally, establish acetone and clear water and be contrast.In every ware, add a slice leaf dish, 25 ± 2 ℃; Raise under the R.H.=65-80% condition, worm to be tried adds processing leaf dish after eating up a slice leaf dish again.The leaf dish quantity that record examination worm is got food is calculated the food refusal rate by formula (1), and beginning one normal blade is raised behind the 48h.
0. died from for 5 instar larvae stages;
1. die from prepupa or turn to lopsided pupa;
2. die from pupa time, growing in the pupa is the adult shape;
3. grown and be the adult shape, but the emergence that can not normally shell;
4. can turn into normal adult.
Add up borer populations at different levels and dead, the borer population of living, press following each index of various calculating:
Figure A20031010587000241
Figure A20031010587000242
Figure A20031010587000243
Testing data sees Table 3:
Table 3 podophyllotoxin derivative is to the biological activity determination result of cabbage caterpillar
Compound 48h food refusal rate developmental index % grows inhibiting rate % corrected mortality
％
Compound 1 95.3 75.0 16.7 75.3
Compound 2 91.2 37.5 58.3 46.7
Compound 3 97.3 22.5 75.5 83.3
Compound 4 90.2 27.5 69.4 80.0
Compound 5 100.0 42.5 52.8 86.7
Compound 6 96.3 32.5 63.9 100.0
Compound 7 88.6 25.0 72.2 68.3
Compound 8 90.2 35.0 61.1 60.0
Compound 9 91.6 90.0 0 100.0
Compound 10 100.0 45.0 50.0 48.3
Compound 11 97.8 37.5 58.3 100.0
Compound 12 100.0 47.5 47.2 66.7
Compound 13 88.5 35.0 61.1 63.5
Compound 14 90.6 27.5 69.4 46.7

Claims (3)

1, a kind of podophyllotoxin series derivates, it is characterized in that: its chemical general formula is:
Figure A2003101058700002C1
Wherein sterie configuration is: C-1, α configuration; C-2 is connected to trans lactonic ring between the C-3, the C-4 position be configured as the β position.
2, podophyllotoxin series derivates according to claim 1, it is characterized in that: wherein the C-4 bit substituent is:
(1)
Figure A2003101058700002C2
Be compound 1, i.e. acetyl table Podophyllum emodi var chinense;
(2) Be compound 2, i.e. propionyl table Podophyllum emodi var chinense;
(3) R=-SH is compound 3, i.e. sulfydryl table Podophyllum emodi var chinense;
(4) R=-SCH 3, be compound 4, i.e. first sulfydryl table Podophyllum emodi var chinense;
(5) R=-SCH 2CH 3, be compound 5, i.e. second sulfydryl table Podophyllum emodi var chinense;
(6) Be compound 6, i.e. thioacetyl table Podophyllum emodi var chinense ester;
(7) Be compound 7, i.e. nicotinic acid table Podophyllum emodi var chinense ester;
(8) Be compound 8, i.e. Yi Yansuan table Podophyllum emodi var chinense ester;
(9) R=-NH 2, be compound 9, promptly amino table Podophyllum emodi var chinense;
(10) R=-N 3, being compound 10, nitrogen table Podophyllum emodi var chinense promptly changes;
(11) R=-NH-C 3H 7, be compound 11, i.e. n-propylamine base table Podophyllum emodi var chinense;
(12) R=-NH-C 4H 9Be compound 12, i.e. n-butyl amine base table Podophyllum emodi var chinense;
(13) R=-SCH 2CH 2CH 3Be compound 13, i.e. n-propyl table Podophyllum emodi var chinense thioether;
(14) R=-OCH 3Be compound 14, i.e. β-methyl ether table Podophyllum emodi var chinense.
3, a kind of application of podophyllotoxin series derivates is characterized in that: described podophyllotoxin series compound thing is used to prevent and treat various agricultural insects such as small cabbage moth, mythimna separata, cabbage caterpillar.
CN 200310105870 2003-10-30 2003-10-30 Podophyllotoxin series derivative and its application Pending CN1590388A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102086208A (en) * 2010-12-10 2011-06-08 兰州大学 4 beta-podophyllotoxin amidine compounds as well as preparation method and application thereof
CN104672249A (en) * 2013-11-26 2015-06-03 上海医药工业研究院 Podophyllotoxin derivative, preparation method thereof, medicinal composition and application thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102086208A (en) * 2010-12-10 2011-06-08 兰州大学 4 beta-podophyllotoxin amidine compounds as well as preparation method and application thereof
CN102086208B (en) * 2010-12-10 2013-01-02 兰州大学 4 beta-podophyllotoxin amidine compounds as well as preparation method and application thereof
CN104672249A (en) * 2013-11-26 2015-06-03 上海医药工业研究院 Podophyllotoxin derivative, preparation method thereof, medicinal composition and application thereof

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