CN105037350A - Harmine compound and applications of harmine compound in prevention and control of peronophthora litchi chen disease - Google Patents
Harmine compound and applications of harmine compound in prevention and control of peronophthora litchi chen disease Download PDFInfo
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- CN105037350A CN105037350A CN201510280179.5A CN201510280179A CN105037350A CN 105037350 A CN105037350 A CN 105037350A CN 201510280179 A CN201510280179 A CN 201510280179A CN 105037350 A CN105037350 A CN 105037350A
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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Abstract
The present invention discloses a harmine compound, wherein the chemical structure formula is represented by a formula (I), R1 is selected from phenyl, p-nitrophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl, p-trifluoromethylphenyl and p-chlorophenyl, R2 is selected from ethyl, isopropyl, 2-pyridyl and 2-chlorophenyl, and R3 is selected from hydrogen and ethyl. According to the present invention, the compound provides good inhibition effects on multiple pathogenic bacteria, especially provides good inhibition and prevention and control effects on peronophthora litchi chen, has advantages of small molecular weight, simple structure, easy synthesis and the like, can effectively inhibit hypha growth, sporangium production and sporangium germination of peronophthora litchi chen, has good potential in prevention and control of peronophthora litchi chen disease, and is expected to become a new pesticide fungicide, such that the small molecule compound of the present invention can be used as the new pesticide for prevention and control of the peronophthora litchi chen disease so as to be developed and can provide the new way and means for prevention and control of the peronophthora litchi chen disease.
Description
Technical field
The invention belongs to the applied technical field of pesticide sterilizing agent medicine.More specifically, a kind of banisterine compounds and the application in control peronophythora litchi thereof is related to.
Background technology
Peronophythora litchi occurs in disease very serious on lichee, cause of disease is a kind of fungi, be called Peronophythora Litchii (PeronophthoralitchiChen), found (ChenCC..SpecialPublicCollegeAgriculture early than 1934 in Taiwan, Natl.TaiwanUniversity, 1961,10:1-37.).This pathogenic fungi extracts flower fringe out from lichee all can cause great harm to fruit maturation and even the whole process of adopting rear accumulating, inflorescence, result sprig, young fruit, carpopodium can be endangered, also maturescent fruit can be endangered, scab in fruit is extended to rapidly full fruit, make whole fruit colour change, come off, cause a large amount of shedding, serious to yield effect.During high humidity, tender leaf also can be fallen ill.This disease to infect required time extremely short, and mostly be rainy weather again between lichee fruiting period, preventing and treating if do not carry out in advance almost every year all can popular (Qi Peikun, etc. Plant Pathology .1984,14 (2): 113-119.), severe patient sickness rate reaches more than 20%-80%.And China cultivates the maximum country of lichee at present in the world, according to statistics, the loss that lichee causes because rotting every year account for ultimate production more than 20% ((1) Hu Xinyu, etc. food and fermentation industries, 2001,27 (4): 47-52; (2) Zhang Xiumei, etc. southern china fruit tree, 2004,33 (5): 53-57).
At present, the pesticide control of peronophythora litchi mostly is chemical agent, as metaxanin, zinc manganese ethylenebisdithiocarbamate, P applied levels missible oil, Pu Like aqua, kasugamycin Cupravit wettable powder, Azoxystrobin, kresoxim-methyl, flumorph, dimethomorph etc., there is certain inhibition to Peronophythora Litchii germ.But, the chemical bactericide commonly used in field as metaxanin produced resistance in various degree (Wu Xianghui, etc. Agriculture of Anhui science, 2005,33 (2): 36-37).Given this, Peronophythora Litchii has medicine to great majority and creates resistance, extremely urgent to newtype drug demand, exploitation is efficient, the novel peronophythora litchi control agent of low toxicity, low residue, and tachnical storage or practical application have active effect.
And plant-sourced novel agrochemical has low toxicity, low residue, the feature such as environmentally friendly, makes it possess boundless development prospect.Banisterine is the natural beta-carboline alkaloid that a class is mainly present in zygophyllaceae Herba pegani harmalae (PeganumharmalaL.), there is outstanding anticancer, desinsection, the multiple biological activity such as antibacterial and antiviral, structure is relatively simple, be easy to modify transformation, investigator pays close attention to extremely both at home and abroad.In recent years, studies have found that to banisterine to multiple germ have very outstanding fungistatic effect ((1) symbol hypo, etc. grassland and lawn, 2008, (1), 44-48; (2) NenaahG.Fitoterapia, 2010,81 (7), 779-782; (3) Yu Zhitong, etc. Journal of Northwest Sci Tech University of Agriculture and Forestry (natural science edition), 2012, (09), 72-76. (4) Liu Jianxin, etc. northwest Botany Gazette, 2003,23,2200-2203; (5) Liu Jianxin, etc. northwest Botany Gazette, 2005,25,1756-1760).But totally it seems, current research contents is mainly for the rough determination of the bacteriostatic activity of banisterine crude extract and simple derivatives, and existing relevant bibliographical information ((1) RharrabeK., etal.PesticideBiochemistryandPhysiology, 2007,89,137-145; (2) Zhang Qianliang, etc. Pesticide Science journal, 2013,15 (4), 388-392; (3) Song, H.etal.Bioorganic & MedicinalChemistryLetters2014,24, (22), 5228-5233.).Current, carrying out the research of control of plant disease application aspect for banisterine compounds as agricultural chemicals reports also very rare, yet there are no this compounds and the research report in control Peronophythora Litchii germ, glue born of the same parents anthrax-bacilus, Rhizoctonia solani Kuhn, Phytophthora nicotianae germ, citric acid maize ear rot bacterium and banana blight bacteria thereof, banisterine compounds is not also deep in the middle of production application.
Summary of the invention
The technical problem to be solved in the present invention is the defect and the deficiency that overcome existing peronophythora litchi Prevention Technique, provides a kind of micromolecular compound suppressing Peronophythora Litchii to grow, and namely banisterine compounds is as the application of control peronophythora litchi sterilant.
The object of this invention is to provide a kind of banisterine compounds and at phytopathogens such as control Peronophythora Litchii germ, glue born of the same parents anthrax-bacilus, Rhizoctonia solani Kuhn, Phytophthora nicotianae germ, citric acid maize ear rot bacterium or banana blight bacterias, especially prevent and treat the application in peronophythora litchi.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of banisterine compounds, its chemical structural formula is such as formula shown in (I):
Wherein, R
1be selected from phenyl, p-nitrophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyls, p-trifluoromethyl phenyl or rubigan; R
2be selected from ethyl, sec.-propyl, 2-pyridyl or 2-chloro-phenyl-; R
3be selected from hydrogen or ethyl.
The application of above-mentioned banisterine compounds in control phytopathogen, and being applied within protection scope of the present invention in the agricultural bactericide of preparation control phytopathogen.
Wherein, preferably, the bacteriostatic activity of described banisterine compounds to Peronophythora Litchii germ, glue born of the same parents anthrax-bacilus, Rhizoctonia solani Kuhn, Phytophthora nicotianae germ, citric acid maize ear rot bacterium or banana blight bacteria is more remarkable.
More preferably, be the most remarkable to the bacteriostatic activity of Peronophythora Litchii germ.
In addition, preferably, when applying, the good banisterine compounds of bacteriostatic activity is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide (F4), N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide (F5), N-(2-pyridyl)-1-p-nitrophenyl-β-carboline-3-methane amide (F9), N-Chloro-O-Phenyl-1-p-nitrophenyl-β-carboline-3-methane amide (F10), N-(2-pyridyl)-1-p-methoxyphenyl-β-carboline-3-methane amide (F14), N, N-diethyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide (F17), N-Chloro-O-Phenyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide (F20), N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F24), N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F25), N, N-diethyl-1-rubigan-β-carboline-3-methane amide (F27) or N-Chloro-O-Phenyl-1-rubigan-β-carboline-3-methane amide (F30).
Wherein, the better described banisterine compounds of bacteriostatic activity is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide (F4), N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide (F5), N-(2-pyridyl)-1-p-nitrophenyl-β-carboline-3-methane amide (F9), N-Chloro-O-Phenyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide (F20), N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F24), N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F25), N, N-diethyl-1-rubigan-β-carboline-3-methane amide (F27) or N-Chloro-O-Phenyl-1-rubigan-β-carboline-3-methane amide (F30).
More preferably, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide (F4), N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide (F5), N-Chloro-O-Phenyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide (F20), N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F24), N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F25) or N, N-diethyl-1-rubigan-β-carboline-3-methane amide (F27).
Most preferably, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide (F4), English name is N-(2-pyridyl)-1-phenyl-9H-pyrido [3,4-b] indole-3-formamide, its molecular formula is C
23h
16n
4o; Molecular weight is 364, and its chemical structural formula is such as formula shown in (II):
The present invention has synthesized the banisterine compounds shown in a series of formula (I), and determine its restraining effect to six kinds of Different Kinds of Pathogens fungies, the candidate compound of 100mg/L adds in the substratum of pathogenic fungi by the present invention, and the cultivation containing candidate compound being vaccinated with pathogenic fungi is cultivated 3-7 days based on 25 DEG C, carry out multilevel iudge pathogenic fungi by right-angled intersection method and whether receive suppression.Then select the pathogenic fungi Peronophythora Litchii Leaf method that the in vitro inhibition of banisterine compounds is best, measure all compounds to the inhibition of Peronophythora Litchii in condition of living body.
Experimental result shows, and most of banisterine compounds all has certain restraining effect to six kinds of Different Kinds of Pathogens fungies, can suppress the mycelial growth of plant pathogenic fungi.Wherein to the Peronophythora Litchii of Oomycete pathogenic fungi and Phytophthora nicotianae inhibition better, and optimum to the inhibition of Peronophythora Litchii.Wherein, F4, F5, F17, F20, F24, F25, F27 create wide spectrum inhibit activities to six kinds of pathogenic fungies, and best to the inhibition of Peronophythora Litchii germ; F9, F10, F14, F30 also have good inhibit activities to Peronophythora Litchii germ.And most of banisterine compounds can show certain protected effect and result for the treatment of to Peronophythora Litchii, and most banisterine compounds is based on protected effect.Wherein especially all show excellent effect with compound F 17-hydroxy-corticosterone 4 compound to the provide protection of Peronophythora Litchii and therapeutic action, protected effect reaches 92.59%, and result for the treatment of is 59.26%.
Comprehensive descision, especially compound F 17-hydroxy-corticosterone 4 are better to the inhibit activities of six kinds of pathogenic fungies, and best to the inhibition of Peronophythora Litchii germ, reach 95.89%; EC
50for 8.6mg/L, EC
95for 86mg/L, show the inhibit activities to Peronophythora Litchii excellence.
In experimentation, the data of banisterine compounds obtain having the compound suppressing Peronophythora Litchii with the data comparative evaluation contrasting medicament metaxanin, and conclusion is more reliable.Also in vitro test is carried out to the sporangial restraining effect of the best compound F 17-hydroxy-corticosterone 4 pairs of Peronophythora Litchiis of the activity filtered out, found the sporangial generation of compound F 17-hydroxy-corticosterone 4 pairs of Peronophythora Litchiis and sprout and have significant restraining effect.
The present invention has following beneficial effect:
The invention discloses one, to multiple pathogenic bacteria, there is better inhibiting banisterine compounds, wherein especially to the suppression of Peronophythora Litchii and prevention effect best, therefore, micromolecular compound of the present invention can be developed as the novel pesticide of control peronophythora litchi, for control peronophythora litchi provides a kind of new approach and means.And there is following significant advantage:
1, the micromolecular compound molecular weight of the present invention's acquisition is little, and structure is relatively simple, and synthesis easily.
2, the micromolecular compound specificity of the present invention's acquisition is good, effectively can suppress the growth of Peronophythora Litchii mycelia, sporangial generation and sprouting.
3, the micromolecular compound that the present invention obtains suppresses the effect of Peronophythora Litchii close to control Peronophythora Litchii medicine metaxanin, and can be better than metaxanin at the Be very effective suppressing Peronophythora Litchii sporocyst to be sprouted.
Embodiment
Further illustrate the present invention below in conjunction with specific embodiment, but embodiment does not limit in any form to the present invention.Unless stated otherwise, the present invention adopts reagent, method and apparatus are the art conventional reagent, method and apparatus.
Unless stated otherwise, following examples agents useful for same and material are commercial.
Embodiment 1N-ethyl-1-phenyl-β-carboline-3-methane amide (F1)
1, steps A: the synthesis of 1-phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (2)
Take 20.4gL-tryptophane (0.1mol) in the there-necked flask that electric mantle and electric mixer are housed, 100mL glacial acetic acid is added under stirring, add 12.25g phenyl aldehyde (0.12mol) simultaneously, after stirring at room temperature 15min, be warmed up to 80 ~ 100 DEG C of reaction 10h, thin-layer chromatography tracks to tryptophane and disappears, stop heating, being cooled to room temperature has precipitation to generate, filter, filtrate reduced in volume, remove excessive acetic acid and water, obtain a large amount of light brown flap, white product is obtained after washing, i.e. 1-phenyl-1, 2, 3, 4-tetrahydro-beta-carboline-3-carboxylic acid, productive rate 85%.
2, step B:1-phenyl-1,2, the synthesis of 3,4-tetrahydro-beta-carboline-3-carboxylate methyl ester (3)
Under cryosel bath, 5mL sulfur oxychloride is slowly dripped in l00mL methyl alcohol, except ice deserted salt is bathed after stirring 15min.14.62g1-phenyl-1 is added in reaction mixture, 2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (0.05mol), after stirring at room temperature 30min, slowly heats up, reflux 6h, thin-layer chromatography is followed the tracks of reaction and is terminated, and decompression steams excessive sulfur oxychloride and solvent, by residue water dissolution and with 10% sodium hydroxide solution regulator solution pH value to 6 ~ 7 after cooling, separate out precipitation, filter, dry, obtain colourless transparent crystal by recrystallizing methanol, i.e. 1-phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylate methyl ester.
The synthesis of 3, step C:1-phenyl-β-carboline-3-carboxylate methyl ester (4)
Take 6.12g1-phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylate methyl ester (0.02mo1), with 50mLN, dinethylformamide dissolves, and cryosel bath and the lower gradation of stirring add 4.5gKMnO
4(0.028mol), a large amount of heat release is reacted.After reaction mixture stirs 1h, TLC shows raw material and disappears, and remove ice bath, stirred overnight at room temperature, suction filtration, filtrate reduced in volume to dry, the solid ethyl alcohol recrystallization obtained, obtains light yellow solid, i.e. 1-phenyl-β-carboline-3-carboxylate methyl ester.
The synthesis of 4, step D:1-phenyl-β-carboline-3-carboxylic acid (6)
Get 3.02g1-phenyl-β-carboline-3-carboxylate methyl ester (0.01mol) in 50mL flask, add 20mL dissolve with ethanol, under heated and stirred, drip the aqueous solution that 1mL contains 0.5g sodium hydroxide, reacting by heating 2h, thin-layer chromatography follows the tracks of reaction process, reaction terminates rear dropping dilute hydrochloric acid and is neutralized to pH5 ~ 6, there is Precipitation, filter and obtain 1-phenyl-β-carboline-3-carboxylic acid, washing and drying.
5, step e: N, N-diethyl-1-phenyl--the synthesis of β-carboline-3-acid amides (7a)
Dry for 2.88g 1-phenyl-β-carboline-3-carboxylic acid (0.01mol) is joined in 50mL flask, add 15mL dichloromethane solvent simultaneously, be fixed on oil bath pan, 3mL sulfur oxychloride is added under stirring, install condensing reflux pipe, moisture eliminator and device for absorbing tail gas additional, heating reflux reaction 1h, makes condensation reflux unit into retrieving arrangement, steam solvent and excessive sulfur oxychloride, obtain grey powder.
6, add 10mL methylene dichloride to dissolve, add 0.88g ethamine (0.012mol) under stirring, continue reaction 1h, then suction filtration, the solid ethyl alcohol recrystallization obtained, finally obtains product N-ethyl-1-phenyl-β-carboline-3-methane amide (F1).
7, product detection data are as follows: productive rate: 79.54%, fusing point: 190-192 DEG C, IR (KBr) cm
-1: 3430 (ν
n-H), 2924,2850 (ν
c-H), 1647 (ν
c=O), 1023 (ν
c-N),
1h-NMR (600MHz, DMSO) δ 11.82 (1H, s, N (9) H, c), 8.82 (1H, s, C (4) H, c), 8.70 (1H, t, J=6.0Hz, CO-NH), 8.43-8.39 (1H, m, C (5) H, c), 8.15 (2H, dd, J=12.3, 5.2Hz, Ph (2, 6) H), 8.03-8.01 (1H, m, C (8) H, c), 7.65 (2H, dd, J=7.4, 6.3Hz, C (7) H, c, Ph (4) H), 7.60-7.57 (2H, m, Ph (3, 5) H), 7.34-7.31 (1H, m, C (6) H, c), 3.44-3.40 (2H, m, CH
2), 1.18 (3H, t, J=7.2Hz, CH
3).
Embodiment 2N, N-diethyl-1-phenyl-β-carboline-3-methane amide (F2)
1, operate same embodiment 1, only in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 57.10%; Fusing point: 210-212 DEG C; IR (KBr) cm
-1: 3449 (ν
n-H), 2918,2851 (ν
c-H), 1623 (ν
c=O), 1022 (ν
c-N);
1h-NMR (600MHz, DMSO) δ 11.71 (1H, s, N (9) H, c), 8.42 (1H, s, C (4) H, c), 8.35 (1H, d, J=7.8Hz, C (5) H, c), 8.02 (2H, d, J=7.4Hz, Ph (2,6) H), 7.67 (1H, d, J=8.2Hz, C (8) H, c), 7.63 (2H, t, J=7.6Hz, Ph (3,5) H), 7.56 (2H, m, J=19.5,7.5Hz, C (7) H, c, Ph (4) H), 7.29 (1H, t, J=7.4Hz, C (6) H, c), 3.50 (4H, m, J=13.7,6.8Hz, CH
2), 1.23-1.18 (6H, m, CH
3).
Embodiment 3N-sec.-propyl-1-phenyl-β-carboline-3-methane amide (F3)
1, operate same embodiment 1, only in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 47.27%, fusing point: 188-191 DEG C, IR (KBr) cm
-1: 3430 (ν
n-H), 2924,2850CH, CH
3, 1647 (ν
c=O), 1252 (ν
c-N),
1h-NMR (600MHz, DMSO) δ 11.82 (1H, s, N (9) H, c), 8.82 (1H, s, C (4) H, c), 8.41 (1H, d, J=7.9Hz, CO-NH), 8.28 (1H, d, J=8.3Hz, C (5) H, c), 8.12 (2H, d, J=7.3Hz, Ph (2, 6) H), 7.67 (3H, dd, J=17.0, 8.1Hz, C (8) H, c, Ph (3, 5) H), 7.59 (2H, dd, J=17.0, 7.7Hz, C (7) H, c, Ph (4) H), 7.35-7.23 (1H, m, C (6) H, c), 4.20 (1H, m, J=13.4, 6.7Hz, CH), 1.26 (6H, d, J=6.6Hz, CH
3).
Embodiment 4N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide (F4)
1, operate same embodiment 1, only in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 81.49%, fusing point: 182-183 DEG C, IR (KBr) cm
-1: 3447,3423 (ν
n-H), 1623 (ν
c=O), 1245 (ν
c-N), 1493 (ν
c=C),
1h-NMR (600MHz, DMSO) δ 12.05 (1H, s, N (9) H, c), 10.66 (1H, s, CO-NH), 9.05 (1H, s, C (4) H, c), 8.88 (1H, s, C (5) H, c), 8.49 (1H, d, J=7.6Hz, Py (3) H), 8.39 (2H, d, J=6.5Hz, Ph (2, 6) H), 8.35 (1H, d, J=7.8Hz, C (8) H, c), 8.13 (1H, d, J=5.7Hz, Py (5) H), 7.72 (1H, s, C (7) H, c), 7.60 (2H, d, J=7.3Hz, Ph (3, 5) H), 7.35 (2H, d, J=7.7Hz, Ph (4) H, C (6) H, c), 7.31 (1H, d, J=6.8Hz, Py (4) H), 7.20 (1H, s, Py (6) H).
Embodiment 5N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide (F5)
1, operate same embodiment 1, only in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 56.98%; Fusing point: 206-207 DEG C; IR (KBr) cm
-1: 3424 (ν
n-H), 1657 (ν
c=O), 1497 (ν
c=C), 742 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 12.07 (1H, s, N (9) H, c), 11.06 (1H, s, CO-NH), 9.02 (1H, s, C (4) H, c), 8.63-8.60 (1H, m, C (5) H, c), 8.49 (1H, d, J=7.8Hz, Ph
2(6) H), 8.19 (2H, d, J=7.2Hz, Ph
1(2,6) H), 7.73 (1H, d, J=8.2Hz, C (8) H, c), 7.70 (2H, t, J=7.6Hz, Ph
1(3,5) H), 7.67-7.61 (2H, m, Ph
2(3) H, C (7) H, c), 7.61-7.60 (1H, m, Ph
1(4) H), 7.45 (1H, t, J=7.7Hz, Ph
2(4) H), 7.36 (1H, t, J=7.4Hz, C (6) H, c), 7.20-7.17 (1H, m, Ph
2(4) H).
Embodiment 6N-ethyl-1-p-nitrophenyl-β-carboline-3-methane amide (F6)
1, operate same embodiment 1, only replace phenyl aldehyde with paranitrobenzaldehyde in step.
2, product monitoring data is as follows: productive rate: 77.82%; Fusing point: 269-272 DEG C; IR (KBr) cm
-1: 3435 (ν
n-H), 2921,2848 (ν
c-H), 1624 (ν
c=O), 1249 (ν
c-N), 1520,1347 (ν
nO2);
1h-NMR (600MHz, DMSO) δ 12.20 (1H, s, N (9) H, c), 9.02 (1H, s, C (4) H, c), 8.48 (2H, d, J=3.1Hz, Ph (2,6) H), 8.47-8.46 (2H, m, Ph (3,5) H), 8.46-8.44 (1H, m, C (5) H, c), 8.32 (1H, d, J=8.7Hz, CO-NH), 7.72 (1H, t, J=7.8Hz, C (8) H, c), 7.63 (1H, dd, J=11.9,4.6Hz, C (7) H, c), 7.37-7.34 (1H, m, C (6) H, c), 2.80 (2H, m, J=11.9,6.0Hz, CH
2), 1.14 (3H, t, J=7.3Hz, CH
3).
Embodiment 7N, N-diethyl-1-p-nitrophenyl-β-carboline-3-methane amide (F7)
1, operate same embodiment 1, only replace phenyl aldehyde with paranitrobenzaldehyde in step, in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 66.08%; Fusing point: 252-254 DEG C; IR (KBr) cm
-1: 3446 (ν
n-H), 2925,2851 (ν
c-H), 1608 (ν
c=O), 1105 (ν
c-N), 1515,1342 (ν
nO2);
1h-NMR (600MHz, DMSO) δ 11.97 (1H, s, N (9) H, c), 8.53 (1H, s, C (4), c), 8.46 (2H, d, J=8.8Hz, Ph (2,6) H), 8.39 (1H, d, J=7.9Hz, C (5) H, c), 8.31 (2H, d, J=8.6Hz, Ph (3,5) H), 7.69 (1H, d, J=8.1Hz, C (8) H, c), 7.61 (1H, t, J=7.7Hz, C (7) H, c), 7.32 (1H, t, J=7.5Hz, C (6) H, c), 3.53-3.46 (4H, m, CH
2), 1.24-1.19 (6H, m, CH
3).
Embodiment 8N-sec.-propyl-1-p-nitrophenyl-β-carboline-3-methane amide (F8)
1, operate same embodiment 1, only replace phenyl aldehyde with paranitrobenzaldehyde in step, in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 84.58%, fusing point: 260-262 DEG C, IR (KBr) cm
-1: 3426 (ν
n-H), 2918,2850CH, CH
3, 1652 (ν
c=O), 1249 (ν
c-N), 1519,1345 (ν
nO2),
1h-NMR (600MHz, DMSO) δ 12.02 (1H, s, N (9) H, c), 8.91 (1H, s, C (4) H, c), 8.47 (2H, d, J=4.8Hz, Ph (2, 6) H), 8.43 (2H, d, J=8.7Hz, Ph (3, 5) H), 8.34 (1H, d, J=8.4Hz, C (5) H, c), 8.31 (1H, d, J=8.6Hz, CO-NH), 7.69 (1H, d, J=8.9Hz, C (8) H, c), 7.66-7.63 (1H, m, C (7) H, c), 7.35 (1H, d, J=7.2Hz, C (6) H, c), 4.22 (1H, m, J=13.5, 6.7Hz, CH), 1.26 (6H, d, J=6.6Hz, CH
3).
Embodiment 9N-(2-pyridyl)-1-p-nitrophenyl-β-carboline-3-methane amide (F9)
1, operate same embodiment 1, only replace phenyl aldehyde with paranitrobenzaldehyde in step, in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 62.69%, fusing point: 253-255 DEG C, IR (KBr) cm
-1: 3427 (ν
n-H), 1625 (ν
c=O), 1321 (ν
c-N), 1601,1495 (ν
c=C), 1519,1348 (ν
nO2),
1h-NMR (600MHz, DMSO) δ 12.15 (1H, s, N (9) H, c), 10.61 (1H, s, CO-NH), 9.02 (1H, s, C (4) H, c), 8.53 (1H, d, J=7.0Hz, C (5) H, c), 8.47 (2H, d, J=4.2Hz, Ph (2, 6) H), 8.31 (2H, d, J=8.7Hz, Ph (3, 5) H), 8.17 (1H, d, J=8.7Hz, Py (3) H), 7.84 (1H, d, J=8.7Hz, C (5) H, c), 7.72 (1H, d, J=2.7Hz, Py (5) H), 7.68-7.65 (1H, m, C (7) H, c), 7.61-7.57 (1H, m, C (6) H, c), 7.37 (1H, d, J=7.5Hz, Py (4) H), 7.35-7.29 (1H, m, Py (6) H).
Embodiment 10N-Chloro-O-Phenyl-1-p-nitrophenyl-β-carboline-3-methane amide (F10)
1, operate same embodiment 1, only replace phenyl aldehyde with paranitrobenzaldehyde in step, in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 43.60%; Fusing point: 277-278 DEG C; IR (KBr) cm
-1: 3439 (ν
n-H), 1629 (ν
c=O), 1495 (ν
c=C), 737 (ν
c-Cl), 1519,1348 (ν
nO2);
1h-NMR (600MHz, DMSO) δ 12.15 (1H, s, N (9) H, c), 10.61 (1H, s, CO-NH), 9.02 (1H, s, C (4) H, c), 8.53 (1H, d, J=6.8Hz, C (5) H, c), 8.47 (2H, d, J=4.2Hz, Ph
1(2,6) H), 8.43 (1H, d, J=8.7Hz, Ph
2(6) H), 8.39-8.37 (1H, m, Ph
2(3) H), 8.31 (2H, d, J=8.7Hz, Ph
1(3,5) H), 8.17 (1H, d, J=8.7Hz, C (8) H, c), 7.84 (1H, d, J=8.7Hz, C (7) H, c), 7.72 (1H, d, J=2.7Hz, Ph
2(5) H), 7.68-7.65 (1H, m, C (6) H, c), 7.37 (1H, d, J=7.5Hz, Ph
2(4) H).
Embodiment 11N-ethyl-1-p-methoxyphenyl-β-carboline-3-methane amide (F11)
1, operate same embodiment 1, only replace phenyl aldehyde with aubepine in step.
2, product monitoring data is as follows: productive rate: 41.48%, fusing point: 171-173 DEG C, IR (KBr) cm
-1: 3429 (ν
n-H), 2923,2853 (ν
c-H), 1653 (ν
c=O), 1249 (ν
c-N), 1249,1119 (ν
c-O-C),
1h-NMR (600MHz, DMSO) δ 11.80 (1H, s, N (9) H, c), 8.76 (1H, s, C (4) H, c), 8.69 (1H, t, J=6.1Hz, CO-NH), 8.39 (1H, t, J=7.2Hz, C (5) H, c), 8.13 (2H, dd, J=9.2, 2.4Hz, Ph (2, 6) H), 7.69 (1H, d, J=8.2Hz, C (8) H, c), 7.58 (1H, dd, J=11.7, 4.6Hz, C (7) H, c), 7.31 (1H, dd, J=14.3, 7.1Hz, C (6) H, c), 7.19 (2H, dd, J=9.8, 6.3Hz, Ph (3, 5) H), 3.89 (3H, s, J=2.9Hz, OCH
3), 3.45-3.38 (2H, m, CH
2), 1.23-1.14 (3H, m, CH
3).
Embodiment 12N, N-diethyl-1-p-methoxyphenyl-β-carboline-3-methane amide (F12)
1, operate same embodiment 1, only replace phenyl aldehyde with aubepine in step, in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 36.66%; Fusing point: 225-226 DEG C; IR (KBr) cm
-1: 3427 (ν
n-H), 2921,2851 (ν
c-H), 1609 (ν
c=O), 1243 (ν
c-N), 1243,1113 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 11.67 (1H, s, N (9) H, c), 8.36 (1H, s, C (4) H, c), 8.35-8.32 (1H, m, C (5) H, c), 7.99 (2H, d, J=8.7Hz, Ph (2,6)), 7.67 (1H, d, J=8.2Hz, C (8) H, c), 7.57 (1H, t, J=7.6Hz, C (7) H, c), 7.28 (1H, t, J=7.5Hz, C (6) H, c), 7.19 (2H, d, J=8.7Hz, Ph (3,5) H), 3.88 (s, 3H, OCH
3), 3.49 (4H, m, J=13.6,6.8Hz, CH
2), 1.23-1.18 (6H, m, CH
3).
Embodiment 13N-sec.-propyl-1-p-methoxyphenyl-β-carboline-3-methane amide (F13)
1, operate same embodiment 1, only replace phenyl aldehyde with aubepine in step, in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 23.92%, fusing point: 188-189 DEG C, IR (KBr) cm
-1: 3430 (ν
n-H), 2924,2850 (ν
c-H), 1648 (ν
c=O), 1176 (ν
c-N), 1248,1176 (ν
c-O-C),
1h-NMR (600MHz, DMSO) δ 11.78 (1H, s, N (9) H, c), 8.77 (1H, s, C (4) H, c), 8.39 (1H, d, J=7.9Hz, C (5) H, c), 8.28 (1H, d, J=8.3Hz, CO-NH), 8.09 (2H, dd, J=6.8, 4.8Hz, Ph (2, 6) H), 7.68 (1H, dd, J=8.6, 2.1Hz, C (8) H, c), 7.60-7.58 (1H, m, C (7) H, c), 7.37-7.26 (1H, m, C (6) H, c), 7.22-7.20 (2H, m, Ph (3, 5) H), 4.21-4.18 (1H, m, CH), 3.89 (3H, s, J=0.9Hz, OCH
3), 1.26 (6H, dd, J=6.6,1.4Hz, CH
3).
Embodiment 14N-(2-pyridyl)-1-p-methoxyphenyl-β-carboline-3-methane amide (F14)
1, operate same embodiment 1, only replace phenyl aldehyde with aubepine in step, in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 40.36%, fusing point: 244-245 DEG C, IR (KBr) cm
-1: 3414,3340 (ν
n-H), 1686 (ν
c=O), 1300 (ν
c-N), 1608,1512 (ν
c=C), 1252,1176 (ν
c-O-C),
1h-NMR (600MHz, DMSO) δ 12.14 (1H, s, N (9) H, c), 10.66 (1H, s, CO-NH), 9.05 (1H, s, C (4) H, c), 8.40 (2H, d, J=4.9Hz, Py (3) H, C (5) H, c), 8.09 (2H, t, J=8.6Hz, Ph (2, 6) H), 7.94-7.91 (2H, m, Py (5) H, C (8), c), 7.73-7.71 (1H, m, C (7) H, c), 7.64-7.62 (1H, m, C (6) H, c), 7.28-7.25 (2H, m, Ph (3, 5) H), 6.98 (1H, d, J=8.8Hz, Py (4) H), 6.88-6.83 (1H, m, Py (6) H), 3.91 (3H, t, J=2.8Hz, OCH
3).
Embodiment 15N-Chloro-O-Phenyl-1-p-methoxyphenyl-β-carboline-3-methane amide (F15)
1, operate same embodiment 1, only replace phenyl aldehyde with aubepine in step, in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 12.66%; Fusing point: 250-251 DEG C; IR (KBr) cm
-1: 3422 (ν
n-H), 1665 (ν
c=O), 1510 (ν
c=C), 746 (ν
c-Cl), 1249,1114 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 12.02 (1H, s, N (9) H, c), 11.08 (1H, s, CO-NH), 8.98 (1H, d, J=13.0Hz, C (4) H, c), 8.62 (1H, d, J=8.1Hz, C (5) H, c), 8.47 (1H, d, J=7.7Hz, Ph
2(6) H), 8.15 (2H, d, J=8.8Hz, Ph
1(2,6) H), 7.74-7.71 (1H, m, C (7) H, c), 7.62 (2H, dd, J=16.7,8.0Hz, C (8) H, c, Ph
2(3) H), 7.46 (1H, t, J=7.8Hz, C (6) H, c), 7.35 (1H, t, J=7.5Hz, Ph
2(5) H), 7.25 (2H, d, J=8.6Hz, Ph
1(3,5) H), 7.19 (1H, t, J=7.7Hz, Ph
2(4) H), 3.91 (3H, s, OCH
3).
Embodiment 16N-ethyl-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide (F16)
1, operate same embodiment 1, only replace phenyl aldehyde with 3,4,5-Trimethoxybenzaldehyde in step.
2, product monitoring data is as follows: productive rate: 54.13%; Fusing point: 241-243 DEG C; IR (KBr) cm
-1: 3429 (ν
n-H), 2925,2850 (ν
c-H), 1653 (ν
c=O), 1250 (ν
c-N), 1250,1104 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 11.73 (1H, s, N (9) H, c), 8.92 (1H, d, J=20.2Hz, C (4) H, c), 8.41 (1H, t, J=7.9Hz, CO-NH), 7.58 (3H, dd, J=11.5,8.2Hz, Ph (2,6) H, C (8) H, c), 7.30 (2H, ddd, J=20.1,13.5,7.1Hz, C (7) H, c, C (6) H, c), 4.02 (3H, s, Ph
1(4) OCH
3), 3.93 (6H, s, Ph
1(3,5) OCH
3), 3.17 (2H, d, J=5.2Hz, CH
2), 1.15 (3H, d, J=2.0Hz, CH
3).
Embodiment 17N, N-diethyl-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide (F17)
1, operate same embodiment 1, only replace phenyl aldehyde with 3,4,5-Trimethoxybenzaldehyde in step, in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 14.84%; Fusing point: 268-270 DEG C; IR (KBr) cm
-1: 3454 (ν
n-H), 2929,2850 (ν
c-H), 1623 (ν
c=O), 1238 (ν
c-N), 1238,1127 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 11.72 (1H, s, N (9) H, c), 8.90 (1H, s, C (4) H, c), 8.42 (1H, d, J=7.8Hz, C (5) H, c), 8.13 (1H, d, J=8.4Hz, C (8) H, c), 7.64-7.54 (3H, m, C (7) H, c, Ph (2,6) H), 7.31 (1H, dd, J=11.4,4.4Hz, C (6) H, c), 4.03 (3H, s, Ph
1(4) OCH
3), 3.93 (6H, s, Ph
1(3,5) OCH
3), 3.31-3.03 (4H, m, CH
2), 1.21 (6H, t, J=6.5Hz, CH
3).
Embodiment 18N-sec.-propyl-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide (F18)
1, operate same embodiment 1, only replace phenyl aldehyde with 3,4,5-Trimethoxybenzaldehyde in step, in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 22.55%; Fusing point: 311-312 DEG C; IR (KBr) cm
-1: 3433 (ν
n-H), 2925,2855 (ν
c-H), 1651 (ν
c=O), 1052 (ν
c-N), 1252,1116 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 11.72 (1H, s, N (9) H, c), 9.03-8.72 (1H, m, CO-NH), 8.44-8.41 (1H, m, C (4) H, c), 8.35 (1H, d, J=7.9Hz, C (5) H, c), 7.67 (1H, dd, J=17.8,8.2Hz, C (8), c), 7.61-7.56 (1H, m, C (7) H, c), 7.29-7.27 (1H, m, C (6) H, c), 7.23 (2H, s, Ph (2,6) H), 3.93-3.90 (6H, m, Ph
1(3,5) OCH
3), 3.78 (3H, d, J=3.0Hz, Ph
1(4) OCH
3), 3.50 (1H, s, CH), 1.23 (6H, m, J=12.5,7.0Hz, CH
3).
Embodiment 19 (N-(2-pyridyl)-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide (F19)
1, operate same embodiment 1, only replace phenyl aldehyde with 3,4,5-Trimethoxybenzaldehyde in step, in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 41.63%, fusing point: 279-281 DEG C, IR (KBr) cm
-1: 3433 (ν
n-H), 1651 (ν
c=O), 1252 (ν
c-N), 1623,1525 (ν
c=C), 1252,1113 (ν
c-O-C),
1h-NMR (600MHz, DMSO) δ 11.89 (1H, s, N (9) H, c), 10.58 (1H, s, CO-NH), 9.09 (1H, s, C (4) H, c), 8.50-8.48 (1H, m, C (5) H, c), 8.37 (1H, d, J=8.3Hz, Py (3) H), .94 (2H, dd, J=16.5, 8.4Hz, C (8) H, c, Py (5) H), 7.63 (2H, d, J=3.1Hz, C (7) H, c, C (6), c), 7.35 (2H, ddd, J=9.6, 6.2, 3.9Hz, Py (4, 6) H), 7.22-7.19 (2H, m, Ph (2, 6) H), 3.95-3.92 (6H, m, Ph (3, 5) OCH
3), 3.87 (3H, s, Ph (4) OCH
3).
Embodiment 20N-Chloro-O-Phenyl-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide (F20)
1, operate same embodiment 1, only replace phenyl aldehyde with 3,4,5-Trimethoxybenzaldehyde in step, in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 10.09%; Fusing point: 275-278 DEG C; IR (KBr) cm
-1: 3429 (ν
n-H), 1624 (ν
c=O), 1484 (ν
c=C), 749 (ν
c-Cl), 1250,1109 (ν
c-O-C);
1h-NMR (600MHz, DMSO) δ 12.11 (1H, s, N (9) H, c), 11.07 (1H, s, CO-NH), 9.54-9.53 (1H, m, C (4) H, c), 9.06 (1H, s, Ph
2(6) H), 9.01 (1H, s, C (5) H, c), 8.51-8.47 (2H, m, C (8), c, Ph
2(6) H), 7.64 (2H, s, C (7), c, C (6) H, c), 7.41 (2H, s, Ph
1(2,6) H), 7.26 (1H, s, Ph
2(5) H), 7.19-7.18 (1H, m, Ph
2(4) H), 3.97-3.92 (6H, m, Ph
1(3,5) OCH
3), 3.80 (3H, s, Ph
1(4) OCH
3).
Embodiment 21N-ethyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F21)
1, operate same embodiment 1, only replace phenyl aldehyde with trifluoromethylated benzaldehyde in step.
2, product monitoring data is as follows: productive rate: 78.10%; Fusing point: 261-263 DEG C; IR (KBr) cm
-1: 3428 (ν
n-H), 2926,2848 (ν
c-H), 1625 (ν
c=O), 1250 (ν
c-N), 1119 (ν
cF3);
1h-NMR (600MHz, DMSO) δ 11.95 (1H, s, N (9) H, c), 8.87 (1H, s, CO-NH), 8.76 (1H, t, J=6.1Hz, C (4) H, c), 8.40 (2H, dd, J=35.2,8.0Hz, Ph (2,6) H), 7.99 (2H, d, J=8.2Hz, Ph (3,5) H), 7.68 (1H, d, J=8.2Hz, C (8) H, c), 7.65-7.58 (1H, m, C (7) H, c), 7.43-7.27 (1H, m, C (6) H, c), 3.38 (2H, q, J=4.3Hz, CH
2), 1.18 (3H, t, J=7.2Hz, CH
3).
Embodiment 22N, N-diethyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F22)
1, operate same embodiment 1, only replace phenyl aldehyde with trifluoromethylated benzaldehyde in step, in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 83.40%; Fusing point: 238-239 DEG C; IR (KBr) cm
-1: 3435 (ν
n-H), 2927,2851 (ν
c-H), 1615 (ν
c=O), 1323 (ν
c-N), 1122 (ν
cF3);
1h-NMR (600MHz, DMSO) δ 11.83 (1H, s, N (9) H, c), 8.49 (1H, s, C (4) H, c), 8.38 (1H, d, J=7.9Hz, C (5) H, c), 8.22 (2H, d, J=8.1Hz, Ph (2,6) H), 7.99 (2H, d, J=8.2Hz, Ph (3,5) H), 7.66 (1H, d, J=8.2Hz, C (8) H, c), 7.60 (1H, t, J=7.6Hz, C (7) H, c), 7.31 (1H, t, J=7.4Hz, C (6) H, c), 3.53-3.47 (4H, m, CH
2), 1.20 (6H, t, J=14.3,7.0Hz, CH
3).
Embodiment 23N-sec.-propyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F23)
1, operate same embodiment 1, only replace phenyl aldehyde with trifluoromethylated benzaldehyde in step, in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 69.30%, fusing point: 245-247 DEG C, IR (KBr) cm
-1: 3437 (ν
n-H), 2925,2854 (ν
c-H), 1646 (ν
c=O), 1325 (ν
c-N), 1122 (ν
cF3),
1h-NMR (600MHz, DMSO) δ 11.95 (1H, s, N (9) H, c), 8.88 (1H, s, C (4) H, c), 8.43 (1H, d, J=7.9Hz, C (5) H, c), 8.33 (3H, d, J=8.0Hz, Ph (3, 5), C (8) H, c), 8.00 (2H, d, J=8.2Hz, Ph (3, 5) H), 7.68 (1H, d, J=8.2Hz, CO-NH), 7.64-7.58 (1H, m, C (7) H, c), 7.33 (1H, dd, J=11.3, 4.2Hz, C (6) H, c), 4.21 (1H, qd, J=13.3, 6.6Hz, CH), 1.25 (6H, d, J=6.6Hz, CH
3).
Embodiment 24N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F24)
1, operate same embodiment 1, only replace phenyl aldehyde with trifluoromethylated benzaldehyde in step, in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 57.70%, fusing point: 269-271 DEG C, IR (KBr) cm
-1: 3438 (ν
n-H), 1627 (ν
c=O), 1322 (ν
c-N), 1524 (ν
c=C), 1121 (ν
cF3),
1h-NMR (600MHz, DMSO) δ 12.15 (1H, s, N (9) H, c), 10.61 (1H, d, J=13.9Hz, CO-NH), 9.10 (1H, s, C (4) H, c), 8.51 (1H, d, J=7.9Hz, C (5) H, c), 8.38 (2H, ddd, J=12.1, 6.9, 3.6Hz, Py (3), C (8) H, c), 8.34 (2H, d, J=8.3Hz, Ph (2, 6) H), 8.06 (2H, d, J=8.1Hz, Ph (3, 5) H), 7.70 (2H, dd, J=16.2, 8.2Hz, C (7, 8) H, c), 7.62-7.57 (1H, m, C (6) H, c), 7.41-7.35 (1H, m, Py (4) H), 7.26-7.14 (1H, m, Py (6) H).
Embodiment 25N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide (F25)
1, operate same embodiment 1, only replace phenyl aldehyde with trifluoromethylated benzaldehyde in step, in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 95.60%; Fusing point: 295-297 DEG C; IR (KBr) cm
-1: 3442 (ν
n-H), 1641 (ν
c=O), 1539 (ν
c=C), 744 (ν
c-Cl), 1116 (ν
cF3);
1h-NMR (600MHz, DMSO) δ 12.17 (1H, s, N (9) H, c), 10.96 (1H, s, CO-NH), 9.05 (1H, s, C (4) H, c), 8.56 (1H, dd, J=8.2,1.5Hz, C (5) H, c), 8.49 (1H, d, J=7.9Hz, Ph
2(6) H), 8.37 (2H, d, J=8.1Hz, Ph
1(2,6) H), 8.04 (2H, d, J=8.2Hz, Ph
1(3,5) H), 7.72 (1H, d, J=8.2Hz, C (8) H, c), 7.67-7.63 (1H, m, Ph
2(3) H), 7.59 (1H, dd, J=8.0,1.4Hz, C (7) H, c), 7.50-7.42 (1H, m, Ph
2(5) H), 7.41-7.33 (1H, m, C (6) H, c), 7.18 (1H, td, J=7.8,1.5Hz, Ph
2(4) H).
Embodiment 26N-ethyl-1-rubigan-β-carboline-3-methane amide (F26)
1, operate same embodiment 1, only replace phenyl aldehyde with 4-chloro-benzaldehyde in step.
2, product monitoring data is as follows: productive rate: 49.84%; Fusing point: 234-236 DEG C; IR (KBr) cm
-1: 3440N-H, 2926,2855 (ν
c-H), 1644 (ν
c=O), 1091 (ν
c-N), 746 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 12.06 (1H, s, N (9) H, c), 8.93 (2H, d, J=10.2Hz, Ph
1(2,6) H), 8.43 (1H, d, J=7.8Hz, CO-NH), 8.07-8.05 (2H, m, C (4,5) H, c), 7.71-7.69 (3H, m, C (8) H, c, Ph
1(3,5) H), 7.63-7.60 (1H, m, C (7) H, c), 7.34 (1H, t, J=7.1Hz, C (6) H, c), 3.93 (2H, m, CH
2), 1.36-1.05 (3H, m, CH
3).
Embodiment 27N, N-diethyl-1-rubigan-β-carboline-3-methane amide (F27)
1, operate same embodiment 1, only replace phenyl aldehyde with 4-chloro-benzaldehyde in step, in step e, replace ethamine with diethylamine.
2, product monitoring data is as follows: productive rate: 25.64%; Fusing point: 247-248 DEG C; IR (KBr) cm
-1: 3436 (ν
n-H), 2925,2855 (ν
c-H), 1626 (ν
c=O), 1093 (ν
c-N), 747 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 11.88 (1H, s, N (9) H, c), 8.82 (1H, s, C (4) H, c), 8.41 (1H, d, J=7.9Hz, C (5) H, c), 8.21-8.19 (2H, m, Ph
1(2,6) H), 7.70-7.68 (3H, m, C (8) H, c, Ph
1(3,5) H), 7.62-7.59 (1H, m, C (7) H, c), 7.32 (1H, t, J=7.1Hz, C (6) H, c), 3.16 (4H, q, J=5.2Hz, CH
2), 1.16 (6H, m, J=26.0,7.2Hz, CH
3).
Embodiment 28N-sec.-propyl-1-rubigan-β-carboline-3-methane amide (F28)
1, operate same embodiment 1, only replace phenyl aldehyde with 4-chloro-benzaldehyde in step, in step e, replace ethamine with Isopropylamine.
2, product monitoring data is as follows: productive rate: 60.15%; Fusing point: 257-259 DEG C; IR (KBr) cm
-1: 3439 (ν
n-H), 2969,2927 (ν
c-H), 1648 (ν
c=O), 1092 (ν
c-N), 746 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 11.87 (1H, s, N (9) H, c), 8.85 (1H, d, J=17.0Hz, C (5) H, c), 8.45-8.28 (2H, m, Ph
1(2,6) H), 8.22-8.07 (2H, m, C (4) H, c, CO-NH), 7.70 (3H, ddd, J=15.4,8.7,5.3Hz, C (8) H, c, Ph
1(3,5) H), 7.64-7.56 (1H, m, C (8) H, c), 7.37-7.28 (1H, m, C (6) H, c), 4.24-4.13 (1H, CH, m), 1.25 (6H, d, J=6.6Hz, CH
3).
Embodiment 29N-(2-pyridyl)-1-rubigan-β-carboline-3-methane amide (F29)
1, operate same embodiment 1, only replace phenyl aldehyde with 4-chloro-benzaldehyde in step, in step e, replace ethamine with 2-pyridine amine.
2, product monitoring data is as follows: productive rate: 7.29%; Fusing point: 263-265 DEG C; IR (KBr) cm
-1: 3436 (ν
n-H), 1628 (ν
c=O), 1455 (ν
c=C), 1094 (ν
c-N), 747 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 12.03 (1H, s, N (9) H, c), 8.93 (1H, s, N (9) H, c), 8.43 (2H, d, J=7.9Hz, Ph
1(2,6) H), 8.10 (3H, t, J=8.5Hz, C (4,5) H, c, Py (3) H), 7.70 (5H, t, J=8.5Hz, C (7,8) H, c, Ph
1(3,5) H, Ph
2(5) H), 7.62 (1H, t, J=7.1Hz, C (6) H, c), 7.32 (2H, dd, J=28.9,21.6Hz, Ph
2(4,6) H).
Embodiment 30N-Chloro-O-Phenyl-1-rubigan-β-carboline-3-methane amide (F30)
1, operate same embodiment 1, only replace phenyl aldehyde with 4-chloro-benzaldehyde in step, in step e, replace ethamine with Ortho-Chloro aniline.
2, product monitoring data is as follows: productive rate: 35.84%; Fusing point: 271-273 DEG C; IR (KBr) cm
-1: 3449 (ν
n-H), 1649 (ν
c=O), 1594,1497 (ν
c=C), 1094 (ν
c-N), 741 (ν
c-Cl);
1h-NMR (600MHz, DMSO) δ 12.16 (1H, s, N (9) H, c), 11.00 (1H, s, CO-NH), 9.02 (1Hs, C (4) H, c), 8.58 (1H, t, J=8.2,4.1Hz, C (5) H, c), 8.49 (1H, d, J=7.9Hz, Ph
2(6) H), 8.24-8.17 (2H, m, Ph
1(3,5) H), 7.78-7.72 (3H, m, Ph
1(3,5) H, Ph
2(3) H), 7.64 (1H, ddd, J=8.2,5.8,1.1Hz, C (8) H, c), 7.60 (1H, dd, J=8.0,1.4Hz, C (7) H, c), 7.47-7.43 (1H, m, Ph
2(5) H), 7.40-7.33 (1H, m, C (6) H, c), 7.22-7.16 (1H, m, Ph
2(4) H).
Embodiment 31 compound biological activity determination
1, reagent agent: the compound synthesized by the embodiment of the present invention 1 ~ 30.
2, compounding method for medicament
Test compound content all calculates with 100%, accurately take test compound 100mg, be dissolved in 1 ~ 2mlDMSO, with acetone constant volume to 10ml or directly with DMSO constant volume to 10ml, obtain 10000mg/L mother liquor, then be diluted to test concentrations with containing 0.05% tween-80 aqueous emulsion, namely obtain certain density test medicine.
3, to phytopathogen activity determination method
(1) for examination pathogenic bacteria: peronophythora litchi (PeronophthoralitchiiChen), banana blight bacteria (Fusariumoxysporumf.sp.cubense), glue born of the same parents anthrax-bacilus (Colletotrichumgloeosporioides (Penz.)), Rhizoctonia solani Kuhn (Rhizoctoniasolani), Phytophthora nicotianae Breda (Phytophthoranicotianae), citric acid maize ear rot bacterium (OosporacitriaurantiiexPersoon) provides by department of plant pathology of resource environment institute of Agricultural University Of South China, this laboratory retains in 1 year for examination.
(2) according to " farm-chemical indoor determination test rule " (The Ministry of Agriculture of the People's Republic of China, MOA, 2006) recommend method, live body pathogenic bacteria mycelial growth rate method and blade method is adopted to carry out.Live body pathogenic bacteria mycelial growth rate method: according to certain concentration gradient, test compounds added through sterilizing and be cooled in the substratum of about 50 DEG C, mixing, is diluted to series concentration and is prepared into pastille substratum by medicament, a bacterium dish (diameter d=0.6cm) inoculated by every culture dish, the ultimate density of test medicament is respectively 500mg/L, 200mg/L, 100mg/L, 50mg/L, 6 gradients such as 25mg/L, 5mg/L, each concentration establishes 3 repetitions; With well metaxanin and harmaline (Harmaline), harmalol (Harmalol), yageine (Harmine), harmol (Harmol) is contrast medicament, measures compound to Peronophythora Litchii inhibit activities; Other pathogenic fungies 100mg/L concentration carries out general sieve.Be cultured at 25 DEG C the colony diameter (cm) measuring each concentration process when contrast bacterium colony covers with culture dish more than 2/3 with right-angled intersection method, get the representative of its mean value, calculate medicament to mycelial growth inhibition ratio and concentration (EC in suppressing
50).
(3) result is as shown in table 1.
Table 1 banisterine compounds is to the restraining effect of six kinds of Different Kinds of Pathogens fungies
Note:
ametaxanin: 10mg/L;
bjingganmycin: 100mg/L;
cderosal: 50mg/L;
d "-"represent there is no activity;
e "/"represent and do not measure.
As can be seen from Table 1, most of banisterine compounds all has certain restraining effect to six kinds of Different Kinds of Pathogens fungies, can suppress the mycelial growth of plant pathogenic fungi.Wherein to the Peronophythora Litchii of Oomycete pathogenic fungi and Phytophthora nicotianae inhibition better, and optimum to the inhibition of Peronophythora Litchii.
In banisterine compounds, F4, F5, F17, F20, F24, F25, F27 create wide spectrum inhibit activities to six kinds of pathogenic fungies, and best to the inhibition of Peronophythora Litchii germ; F9, F10, F14, F30 also have good inhibit activities to Peronophythora Litchii germ.
Comprehensive descision, especially compound F 17-hydroxy-corticosterone 4 are better to the inhibit activities of six kinds of pathogenic fungies, and best to the inhibition of Peronophythora Litchii germ, reach 95.89%.
(4) result is as shown in table 2.
Table 2 banisterine compounds is to the inhibiting virulence of Peronophythora Litchii
As can be seen from Table 2, part banisterine compounds shows excellent inhibit activities to Peronophythora Litchii, EC
50be worth at below 200mg/L, the wherein EC of F4 compound
50for 8.6mg/L, EC
95for 86mg/L, show the inhibit activities to Peronophythora Litchii excellence.
4, blade method:
(1) protectiveness test: get tender leaf of uniform size on the tender tip of litchi, clear water rinses 3 times, blots surperficial water droplet with thieving paper, is that the liquid of 100mg/L evenly sprays in vacuum side of blade by concentration, after liquid natural air drying, preparation is containing 1 × 10
5the sporangia suspension of individual/mL, evenly spray is shone at blade surface, is placed in and is placed with in the large culture dish of moistening filter paper.Be inoculated on blade, be placed in 20 DEG C, relative humidity 70% ~ 80%, cultivated in the constant incubator of day every day illumination 12h.Curative tests: key step is identical with the key step that protectiveness is tested, no is first connect bacterium, sprays medicine in 1 day.Observe incidence, when contrast 80% blade onset area is more than 50%, the morbidity progression of investigating, calculates disease index.Disease scale is as follows:
0 grade, onset area is 0;
1 grade, onset area is less than 5% of whole blade area;
3 grades, onset area is more than or equal to 5%, is less than 10%;
5 grades, onset area is more than or equal to 10%, is less than 20%;
7 grades, onset area is more than or equal to 20%, is less than 50%;
9 grades, onset area is more than or equal to 50%.
According to formula (1), (2) calculate the disease index of incidence of leaf and the fungistatic effect of medicament respectively.
(2) result is as shown in table 3.
Table 3 Litchi Leaves method test banisterine compounds is to the restraining effect of Peronophythora Litchii
Note:
ametaxanin: 10mg/L;
b "/"represent and do not measure.
As can be seen from Table 2, most of banisterine compounds can show certain protected effect and result for the treatment of to Peronophythora Litchii, and based on protected effect.Wherein compound F 17-hydroxy-corticosterone 4 compound all shows excellent effect to the provide protection of Peronophythora Litchii and therapeutic action, and protected effect reaches 92.59%, and result for the treatment of is 59.26%.
5, F4 restraining effect that Peronophythora Litchii sporocyst is sprouted
(1) by the Peronophythora Litchii after PDA substratum cultivates 7 days at 25 DEG C, with sterilized water wash-out sporocyst, filter through four layers of sterile gauze, be prepared into sporangia suspension.Being adjusted to concentration with blood cell counting plate is 1 × 10
5cfu/ml, for subsequent use.In 24 orifice plates, add 100 μ L sporangia suspensions respectively, 280mlPDA and 20 μ L liquids, be worth containing 0,8.6, the sporocyst treatment solution of 86mg/L, 25 DEG C of cultivations after mixing.Observe sprouting situation at inverted microscope after 12h and carry out experimental record.Using 6.3mg/L metaxanin as positive control, each process in triplicate.
Method of calculation:
In formula: R-spore germination rate; N
g-spore germination number; N
t-investigation spore sum.
In formula: R
e-process corrects spore germination rate; R
t-process spore germination rate; R
0-blank spore germination rate.
In formula: I-spore germination relative inhibition; R
0-blank spore germination rate; R
e-process corrects spore germination rate
(2) result is as shown in table 4.
Table 4F4 is to the sporangial influence of Peronophythora Litchii
As can be seen from Table 4, the sporocyst of F4 compound to Peronophythora Litchii has the inhibit activities of highly significant.The concentration of F4 is at 8.6mg/L (EC
50) time, inhibiting rate is formed up to more than 95%, with control group metaxanin at 6.3mg/L (EC to the sporocyst of Peronophythora Litchii
95) time suitable.
The concentration of F4 is at 8.6mg/L (EC
50) time, be 28.32% to the sporocyst germination rate of Peronophythora Litchii, be significantly higher than control group metaxanin at 6.3mg/L (EC
95) time sporocyst germination rate (6.90%).
The concentration of F4 is at 86mg/L (EC
95) time, to the sporocyst germination rate of Peronophythora Litchii up to 72.46%.
Claims (9)
1. a banisterine compounds, is characterized in that, the chemical structural formula of described compound as shown in the formula (I):
Wherein, R
1be selected from phenyl, p-nitrophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyls, p-trifluoromethyl phenyl or rubigan; R
2be selected from ethyl, sec.-propyl, 2-pyridyl or 2-chloro-phenyl-; R
3be selected from hydrogen or ethyl.
2. the application of banisterine compounds described in claim 1 in control phytopathogen.
3. the application of banisterine compounds described in claim 1 in the agricultural bactericide of preparation control phytopathogen.
4. apply according to Claims 2 or 3, it is characterized in that, described phytopathogen is Peronophythora Litchii germ, glue born of the same parents anthrax-bacilus, Rhizoctonia solani Kuhn, Phytophthora nicotianae germ, citric acid maize ear rot bacterium or banana blight bacteria.
5. apply according to Claims 2 or 3, it is characterized in that, described phytopathogen is Peronophythora Litchii germ.
6. apply according to Claims 2 or 3, it is characterized in that, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-nitrophenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-p-nitrophenyl-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-methoxyphenyl-β-carboline-3-methane amide, N, N-diethyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide, N, N-diethyl-1-rubigan-β-carboline-3-methane amide or N-Chloro-O-Phenyl-1-rubigan-β-carboline-3-methane amide.
7. apply according to Claims 2 or 3, it is characterized in that, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-nitrophenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-(3, 4, 5-trimethoxyphenyl)-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide, N, N-diethyl-1-rubigan-β-carboline-3-methane amide or N-Chloro-O-Phenyl-1-rubigan-β-carboline-3-methane amide.
8. apply according to Claims 2 or 3, it is characterized in that, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-(3,4,5-trimethoxyphenyl)-β-carboline-3-methane amide, N-(2-pyridyl)-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide, N-Chloro-O-Phenyl-1-p-trifluoromethyl phenyl-β-carboline-3-methane amide or N, N-diethyl-1-rubigan-β-carboline-3-methane amide.
9. apply according to Claims 2 or 3, it is characterized in that, described banisterine compounds is N-(2-pyridyl)-1-phenyl-β-carboline-3-methane amide, its chemical structural formula as shown in the formula (II):
。
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| CN105837569A (en) * | 2016-04-29 | 2016-08-10 | 华南农业大学 | Harmaline oxazoline compound and preparation method and application thereof |
| CN105859713A (en) * | 2016-04-29 | 2016-08-17 | 华南农业大学 | Banisterine oxazoline derivate and preparation method and application thereof |
| CN106566870A (en) * | 2016-08-31 | 2017-04-19 | 泰山医学院 | Method for high-throughput rapid screening of fungi antagonistic bacteria |
| CN107372625A (en) * | 2017-08-11 | 2017-11-24 | 潍坊华诺生物科技有限公司 | A kind of soil fungicides of Han hymexazos and its application in planting lawn |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105211137A (en) * | 2015-11-13 | 2016-01-06 | 汪恒森 | Lichee agricultural chemicals of a kind of anti-sour rot and preparation method thereof |
| CN105837569A (en) * | 2016-04-29 | 2016-08-10 | 华南农业大学 | Harmaline oxazoline compound and preparation method and application thereof |
| CN105859713A (en) * | 2016-04-29 | 2016-08-17 | 华南农业大学 | Banisterine oxazoline derivate and preparation method and application thereof |
| CN105859713B (en) * | 2016-04-29 | 2017-08-08 | 华南农业大学 | A kind of harmel alkali oxazole oxazoline derivates and its preparation method and application |
| CN105837569B (en) * | 2016-04-29 | 2017-12-26 | 华南农业大学 | A kind of harmel Jian oxazoline compounds and its preparation method and application |
| CN106566870A (en) * | 2016-08-31 | 2017-04-19 | 泰山医学院 | Method for high-throughput rapid screening of fungi antagonistic bacteria |
| CN107372625A (en) * | 2017-08-11 | 2017-11-24 | 潍坊华诺生物科技有限公司 | A kind of soil fungicides of Han hymexazos and its application in planting lawn |
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