CN110452130A - A kind of Obovatol Mannich base analog derivative and the preparation method and application thereof - Google Patents
A kind of Obovatol Mannich base analog derivative and the preparation method and application thereof Download PDFInfo
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- CN110452130A CN110452130A CN201910825731.2A CN201910825731A CN110452130A CN 110452130 A CN110452130 A CN 110452130A CN 201910825731 A CN201910825731 A CN 201910825731A CN 110452130 A CN110452130 A CN 110452130A
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- A—HUMAN NECESSITIES
- 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
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/08—Amines; Quaternary ammonium compounds containing oxygen or sulfur
- A01N33/10—Amines; Quaternary ammonium compounds containing oxygen or sulfur having at least one oxygen or sulfur atom directly attached to an aromatic ring system
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- A—HUMAN NECESSITIES
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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- A—HUMAN NECESSITIES
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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- A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07D295/205—Radicals derived from carbonic acid
Abstract
The present invention provides a kind of Obovatol Mannich base analog derivatives, have the structural formula as described in chemical general formula:Preparation method is additionally provided, Obovatol is dissolved in dehydrated alcohol, 37% formalin and secondary amine is added, is concentrated under reduced pressure after oil bath, reflux, silica gel thin-layer chromatography separation obtains Obovatol Mannich base analog derivative.The Obovatol Mannich base analog derivative bactericidal activity with higher of preparation, 6,7 and 18 pairs of tomato early blight bacteriums of derivative have in vitro inhibitory activity；1,2,6,7 and 8 pair of Beancurd sheet reaping hook germ of derivative has in vitro inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of botrytis cinerea of derivative has in vitro inhibitory activity；Derivative 1 and 14 pair cucumber anthracnose has in vitro inhibitory activity；6,8 and 14 pairs of capsicum wilt bacterium of derivative have in vitro inhibitory activity；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro inhibitory activity, can be used for controlling plant disease.
Description
Technical field
The invention belongs to fungicide synthesis technical fields, and in particular to a kind of Obovatol Mannich base analog derivative and its
Preparation method and application.
Background technique
Obovatol is from the leaf and bark of Magnoliacea plant somewhat-white magnolia (Magnolia obovata Thunb)
A kind of isolated lignanoids Obovatol Mannich base analog derivative with novel biphenyl ether structure is extracted,
The chemical general formula of Obovatol isBecause it is living with extensive biology
Property and become research hotspot in recent years.Document [Choi, N.H., Choi, G.J., Min, B.S., Jang, K.S., Choi,
Y.H.,Kang,M.S.,Park,M.S.,Choi,J.E.,Bae,B.K.,Kim,J.C.Effects of neolignans
from the stem bark ofMagnolia obovata on plant pathogenic
Fungi.J.App.Microbiol.2009,106 (6): 2057-2063.] Obovatol is reported to seven kinds of plant pathogenic fungis
Inhibiting effect.
Since Obovatol belongs to polyphenols, containing independent catechol structure, this class formation is in vivo
Since the protective effect of cell tissue and various enzymes can be stabilized, but living tissue is once left, due to by nature light
According to and the effects of air oxidation, structure will be not easy to keep original stable type.
At this stage, although having the document report antibacterial action of Obovatol, without its derivative of literature research
Or the like antibacterial effect, more lack the research of its antibacterial structure-activity relationship and antibacterial action mechanism, this is also greatlyed restrict
The further investigation that such compound and its derivative antibacterial are acted on.And there are no the sterilizations containing this class formation on current market
Agent, thus it is derivative to have synthesized serial Mannich bases by structural modification design using Obovatol as lead compound by the present invention
Object, it is intended to screen novel antibacterial bioactive molecule, lay the foundation for exploitation green plants source antibacterial agent, so Obovatol Mannich
The synthesis of bases derivative and its activity research in terms of anti-plant pathogenic fungi have very strong novelty.
Summary of the invention
Technical problem to be solved by the present invention lies in view of the above shortcomings of the prior art, provide a kind of Obovatol
Different substituent groups is imported prepared by Obovatol by Mannich base analog derivative and the preparation method and application thereof, this method
Obovatol Mannich base analog derivative, obtains the higher new construction of bioactivity, and the Obovatol Mannich bases of preparation spreads out
Biology bactericidal activity with higher, 6,7 and 18 pairs of tomato early blight bacteriums of derivative have in vitro inhibitory activity；Derivative 1,2,
6,7 and 8 pairs of Beancurd sheet reaping hook germs have in vitro inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of tomato of derivative
Ash arrhizus bacteria has in vitro inhibitory activity；Derivative 1 and 14 pair cucumber anthracnose has in vitro inhibitory activity；Derivative 6,8
There is in vitro inhibitory activity with 14 pairs of capsicum wilt bacterium；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro inhibit
Activity
In order to solve the above technical problems, the technical solution adopted by the present invention is that: a kind of Obovatol Mannich bases is derivative
Object, the Obovatol Mannich base analog derivative have structural formula shown in following chemical general formula:
The structural formula of R is any one of following structural formula in the structural formula:
Successively it is named as 1~derivative of derivative 21.
The present invention also provides the method for above-mentioned Obovatol Mannich base analog derivative, this method are as follows:
Obovatol is dissolved in dehydrated alcohol, 37% formalin and secondary amine is then sequentially added, is transferred to temperature
For in 40 DEG C~60 DEG C of oil baths, back flow reaction 6h~for 24 hours, and with thin-layer chromatography tracing detection, when the Obovatol disappears
Afterwards, cooled to room temperature is concentrated under reduced pressure, is separated with silica gel thin-layer chromatography, obtain Obovatol Mannich base analog derivative.
Preferably, the amount ratio of the Obovatol, secondary amine, 37% formalin and dehydrated alcohol is 1mmol:
3mmol:3mmol:5mL.
Preferably, the secondary amine is dimethylamine, diethylamine, pyrrolidines, morpholine, thiomorpholine, 1- methyl piperazine, 1- second
Base piperazine, 1- (2- methoxy ethyl) piperazine, 1- Acetylpiperazine, N- piperazinecarboxylic acid ethyl ester, 1-php, 1- (3- methyl
Phenyl) piperazine, 1- (3- methoxyphenyl) piperazine, pipecoline, 3- methyl piperidine, 4- methyl piperidine, 3,5- dimethyl piperazine
Pyridine, 4- piperidine methyl formate, ethyl nipecotate, 4- Phenylpiperidine or 4- benzyl piepridine.
The present invention also provides the application of above-mentioned Obovatol Mannich base analog derivative, the Obovatol Mannich
In bases derivative, 6,7 and 18 pairs of tomato early blight bacteriums of derivative have in vitro inhibitory activity；1,2,6,7 and 8 pair of corruption of derivative
Skin reaping hook germ has in vitro inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of botrytis cinerea tool of derivative
There is in vitro inhibitory activity；Derivative 1 and 14 pair cucumber anthracnose has in vitro inhibitory activity；6,8 and 14 pairs of capsicums of derivative
Wilt has in vitro inhibitory activity；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro inhibitory activity.
Compared with the prior art, the present invention has the following advantages:
1, different substituent groups is imported the Obovatol Mannich base analog derivative of Obovatol preparation by the present invention, is obtained
To the higher new construction of bioactivity, the Obovatol Mannich base analog derivative bactericidal activity with higher of preparation derives
6,7 and 18 pairs of tomato early blight bacteriums of object have in vitro inhibitory activity；1,2,6,7 and 8 pair of Beancurd sheet reaping hook germ of derivative have from
Body inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of botrytis cinerea of derivative has in vitro inhibitory activity；Spread out
1 and 14 pair of cucumber anthracnose of biology has in vitro inhibitory activity；6,8 and 14 pairs of capsicum wilt bacterium of derivative have in vitro suppression
System activity；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro inhibitory activity.
2, the part Obovatol Mannich base analog derivative being related to, its antibacterial for parent Obovatol are invented
Activity increases, the inhibition spore of 2,7 and 14 pairs of botrytis cinereas of derivative 2 and 7 pair Beancurd sheet reaping hook germ and derivative
Sub- germination activity is above Obovatol；The mycelia of derivative 6 and 7 pair tomato early blight bacterium grows in vitro inhibitory activity, derivative
The mycelia of 1,4,6,7 and 8 pair of Beancurd sheet reaping hook germ of object grows in vitro inhibitory activity, derivative 1,3,5,6,7,8,10,12,13,
14, the mycelia of 15,18,20 and 21 pairs of botrytis cinereas grows in vitro inhibitory activity, derivative 1 and 14 pair cucumber anthracnose
Mycelia grow in vitro inhibitory activity, the mycelia of 6,8 and 14 pairs of capsicum wilt bacterium of derivative grow in vitro inhibitory activity and
The mycelia of 1,3,7 and 16 pair of apple anthrax bacteria of derivative grows in vitro inhibitory activity and is superior to Obovatol.And it is bigger
Effect is that the unstability of Obovatol structure can be made up, is introduced by Mannich reaction in the adjacent hydroxyl position of Obovatol
Amine-methylated structure, facilitates the decline of electron rich density in adjacent diphenol structure, can improve Obovaol's to a certain extent
Naturally occurring stable type increases the potentiality of its practical application.Meanwhile the substituent group by introducing various structures can prepare class
Type derivative abundant to obtain the different compound of antibacterial activity, and then enriches the antimicrobial spectrum of this class formation.
Invention is further described in detail with reference to the accompanying drawings and examples.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy spectrogram of derivative 11 prepared by the embodiment of the present invention 1.
Fig. 2 is the carbon-13 nmr spectra spectrogram of derivative 11 prepared by the embodiment of the present invention 1.
Fig. 3 is the nuclear magnetic resonance spectroscopy spectrogram of derivative 20 prepared by the embodiment of the present invention 1.
Fig. 4 is the carbon-13 nmr spectra spectrogram of derivative 20 prepared by the embodiment of the present invention 1.
Fig. 5 is the Obovatol Mannich base analog derivative of the embodiment of the present invention 2 to Four Plants disease fungus spore
Inhibiting germination effect.
Fig. 6 is the Obovatol Mannich base analog derivative of the embodiment of the present invention 2 to six kinds of plant pathogenic fungi mycelia
The inhibitory effect of growth.
Specific embodiment
Embodiment 1
The Obovatol Mannich base analog derivative of the present embodiment, the Obovatol Mannich base analog derivative have such as
Structural formula shown in lower chemical general formula:
The present embodiment additionally provides the method for above-mentioned Obovatol Mannich base analog derivative, this method are as follows:
The Obovatol of 1mmol is dissolved in 5mL dehydrated alcohol, 37% formalin of 3mmol is then sequentially added
With the secondary amine of 3mmol, it is transferred in the oil bath that temperature is 40 DEG C~60 DEG C, back flow reaction 6h~for 24 hours, and tracked with thin-layer chromatography
Detection, after the Obovatol disappears, cooled to room temperature is concentrated under reduced pressure, is separated, obtained with silica gel thin-layer chromatography
Obovatol Mannich base analog derivative.
The R for the Obovatol Mannich base analog derivative that secondary amine is prepared using different raw materials in the above-mentioned methods
The Obovatol Mannich base analog derivative being prepared is respectively designated as 1~derivative of derivative 21 by difference, preparation
The physical property and nuclear magnetic data of Obovatol Mannich base analog derivative (1~derivative of derivative 21) as shown in table 1~2,
Fig. 1~4 are nuclear magnetic resonance spectroscopy and carbon the spectrum spectrogram of derivative 11 and derivative 20.
The physical property of 1 Obovatol Mannich base analog derivative of table
Note: "/" is indicated without measurement in table.
The nuclear-magnetism and high resolution mass spec data of 2 Obovatol Mannich base analog derivative of table
Embodiment 2
The present embodiment is Obovatol Mannich base analog derivative (1~derivative of derivative that embodiment 1 is prepared
21) antibacterial activity test:
1, test plant disease fungus: tomato early blight bacterium (Alternaria solani), Beancurd sheet reaping hook germ
(Fusarium solani), botrytis cinerea (Botrytis cinerea), cucumber anthracnose (Colletotrichum
Orbiculare), capsicum wilt bacterium (Fusarium oxysporum), apple anthrax bacteria (Colletotrichum
Gloeosporioides), provided by agricultural college, Agricultural University Of Shanxi Plant Pathology laboratory.Before all strain uses for examination
It is activated on PDA (potato dextrose agar) culture medium at 25 DEG C ± 1 DEG C for several times, after its recovery to normal vital
It is tested for antibacterial activity.
2, sample and reagent:
Test sample:
The Obovatol Mannich base analog derivative (1~derivative of derivative 21) that embodiment 1 is prepared；
Comparison medicament:
Obovatol, 99% hymexazol raw medicine, 98% difenoconazole technical material and 98% carbendazim active compound；
Solvent:
DMSO (dimethyl sulfoxide) (chromatographically pure), acetone (analysis is pure), emulsifier is Tween-80 (excellent pure grade).
3, antibacterial activity method:
A, using inhibition spore germination method: by activated test plant disease fungus (tomato early blight bacterium, Beancurd sheet reaping hook
Germ, botrytis cinerea, cucumber anthracnose) in cultivated respectively in PDA culture medium a couple of days until its produce spore.Then by bacterium colony
It gently scrapes, aseptic water washing 3 times, double gauze filtering.Finally with the concentration of aseptic aqueous solution adjusting spore suspension to 100
About 30~40, each visual field spore, that is, be made the spore suspension to be tested used under power microscope.All test samples are used
DMSO dissolution after, with 0.1% Tween-80 aseptic aqueous solution be diluted to suitable concentration (final organic solvent content be no more than 2%,
v/v).30 μ L mixed liquors are taken to be added dropwise in the small of concave slide after isometric spore suspension and prepared medical fluid are mixed well
In groove, each chemicals treatment is repeated 3 times, and setting is free of the blank control test of medicament.Concave slide is placed in shoaling layer
Certain time is cultivated under preference temperature in culture dish, it is micro- when the spore germination rate to blank photo group reaches 90% or more
Under the microscope, and according to formula -1 spore germination rate of each chemicals treatment group is calculated, and corresponding correction is calculated according to formula -2
Inhibition of germination, while each medicament is found out in the inhibition of various pathogenic bacteria spore germination using SPSS statistical analysis software
Concentration (IC50), standard deviation (SD) and corresponding 95% confidence interval (95%CI) etc..Measurement result is shown in Fig. 5 ("/" in Fig. 5
Indicate undetermined).The Spore germination conditions of capsicum wilt bacterium and apple anthrax bacteria are more harsh, are less suitable for using inhibition
Spore germination method measures its antibacterial activity；
Spore germination rate=sprouting spore count/statistics spore sum × 100% (formula -1)
Correction inhibition of germination=(control group be averaged spore germination rate-processing group be averaged spore germination rate)/compares
Group is average spore germination rate × 100% (formula -2)
As shown in Figure 5, in inhibiting spore germination test, derivative 7 and derivative 18 to tomato early blight bacterium spore, spread out
Biology 2 and derivative 7 sprout Fusarium solani and derivative 2, derivative 7 and derivative 14 to the spore of botrytis cinerea
Sending out inhibiting rate has been more than two kinds of positive control medicaments (99% hymexazol raw medicine and 98% difenoconazole technical material), is enriched such
Antibacterial structure lays the foundation for further design screening high-efficiency antimicrobial structure, therefore is expected to be used for being prepared into efficient, less toxic novel
Plant source spore germination inhibitor.The derivative of high antibacterial activity is obtained by the structure of modification to Obovatol.
The Obovatol Mannich base analog derivative that the present embodiment is related to, enriches antibacterial structure, because of its precursor structure source
From Secondary metabolites, the process of plant long-term evolution experienced, therefore its environment compatibility is preferable, bioactivity is higher,
And compared with chemical antibacterial agent, may have the characteristics such as low-residual, degradable, it is environmentally friendly.
B, using mycelial growth rate measuring method: by the PDA culture medium melted same after all test sample acetone solutions
It mixes, pours into sterile petri dish, every ware about 15mL, it is the pastille culture medium of 100 μ g/mL (in pastille culture medium that concentration, which is made,
The content of acetone is no more than 0.5%, v/v).It, will be activated in advance for trying strain along bacterium colony side after culture medium cooled and solidified
Edge makes into the bacteria cake that diameter is 4mm, is inoculated in the centre of pastille culture medium, and each medicament is repeated 3 times, while setting is free of
The blank control test of medicament.It is when culture reaches the 2/3 of culture dish diameter to blank control group colony diameter under preference temperature
Only, the colony diameter that each processing group and control group are measured using crossing method calculates the mycelia growth suppression of each chemicals treatment group
Rate processed, while calculating corresponding standard deviation etc..Measurement result is shown in Fig. 6.
Mycelial growth inhibition rate=(control group average colony diameter-processing group average colony diameter)/(control group is averaged bacterium
Fall diameter -4mm) × 100%
It will be appreciated from fig. 6 that inhibit in mycelia growth test, in the case where 100 μ g/mL are for trying concentration, derivative 6 and 7 pair tomato
Early epidemic germ has certain inhibiting effect；The in vitro inhibition with higher to Beancurd sheet reaping hook germ of derivative 1,6,7 and 8 is lived
Property；The in vitro inhibitory activity with higher to botrytis cinerea of derivative 1,3,6,7,8,12,14,15,18 and 21；Derivative
1 and 14 pair of cucumber anthracnose in vitro inhibitory activity with higher；6,8 and 14 pairs of capsicum wilt bacterium of derivative have higher
In vitro inhibitory activity；The in vitro inhibitory activity with higher to apple anthrax bacteria of derivative 1,3,7 and 16.And it is certain
The inhibiting rate of Obovatol Mannich base analog derivative is even near or above two kinds of positive control medicament (99% hymexazols
Medicine and 98% carbendazim active compound), such as: the mycelia growth inhibition effect and derivative of 3,6 and 7 pairs of botrytis cinereas of derivative
1, the mycelia growth inhibition effect of 3,7 and 16 pairs of apple anthrax bacterias has been more than two kinds of positive control medicaments.Thus it is expected to
It is used to prepare new and effective plant-source antibacterial agent
Shown in sum up, by inhibiting spore germination method and mycelial growth rate measuring method it is found that prepared by embodiment 1
In Obovatol Mannich base analog derivative, 6,7 and 18 pairs of tomato early blight bacteriums of derivative have in vitro inhibitory activity；Derivative
1,2,6,7 and 8 pairs of Beancurd sheet reaping hook germs have in vitro inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of derivative
Botrytis cinerea has in vitro inhibitory activity；Derivative 1 and 14 pair cucumber anthracnose has in vitro inhibitory activity；Derivative
6,8 and 14 pairs of capsicum wilt bacterium have in vitro inhibitory activity；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro suppression
System activity.
The above is only presently preferred embodiments of the present invention, is not intended to limit the invention in any way.It is all according to invention skill
Art any simple modification, change and equivalence change substantially to the above embodiments, still fall within technical solution of the present invention
Protection scope in.
Claims (5)
1. a kind of Obovatol Mannich base analog derivative, which is characterized in that the Obovatol Mannich base analog derivative
With structural formula shown in following chemical general formula:
The structural formula of R is any one of following structural formula in the structural formula:
According to
It is secondary to be named as 1~derivative of derivative 21.
2. a kind of method for preparing Obovatol Mannich base analog derivative as described in claim 1, which is characterized in that the party
Method are as follows:
Obovatol is dissolved in dehydrated alcohol, 37% formalin and secondary amine are then sequentially added, being transferred to temperature is 40
DEG C~60 DEG C of oil bath in, back flow reaction 6h~for 24 hours, and with thin-layer chromatography tracing detection, after the Obovatol disappears, from
It is so cooled to room temperature, is concentrated under reduced pressure, is separated with silica gel thin-layer chromatography, obtain Obovatol Mannich base analog derivative.
3. according to the method described in claim 2, it is characterized in that, the Obovatol, secondary amine, 37% formalin and
The amount ratio of dehydrated alcohol is 1mmol:3mmol:3mmol:5mL.
4. according to the method in claim 2 or 3, which is characterized in that the secondary amine be dimethylamine, diethylamine, pyrrolidines,
Morpholine, thiomorpholine, 1- methyl piperazine, 1- ethyl piperazidine, 1- (2- methoxy ethyl) piperazine, 1- Acetylpiperazine, N- piperazine
Ethyl formate, 1-php, 1- (3- aminomethyl phenyl) piperazine, 1- (3- methoxyphenyl) piperazine, pipecoline, 3- methyl
Piperidines, 4- methyl piperidine, 3,5- lupetidine, 4- piperidine methyl formate, ethyl nipecotate, 4- Phenylpiperidine or 4- benzyl
Phenylpiperidines.
5. a kind of application of Obovatol Mannich base analog derivative as described in claim 1, which is characterized in that described
In Obovatol Mannich base analog derivative, 6,7 and 18 pairs of tomato early blight bacteriums of derivative have in vitro inhibitory activity；Derivative
1,2,6,7 and 8 pairs of Beancurd sheet reaping hook germs have in vitro inhibitory activity；1,2,3,6,7,8,12,14,15,18 and 21 pair of derivative
Botrytis cinerea has in vitro inhibitory activity；Derivative 1 and 14 pair cucumber anthracnose has in vitro inhibitory activity；Derivative
6,8 and 14 pairs of capsicum wilt bacterium have in vitro inhibitory activity；1,3,7 and 16 pair of apple anthrax bacteria of derivative has in vitro suppression
System activity.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20010001237A (en) * | 1999-06-02 | 2001-01-05 | 복성해 | Antifungal agent containing obovatol or redobovatol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010001237A (en) * | 1999-06-02 | 2001-01-05 | 복성해 | Antifungal agent containing obovatol or redobovatol |
Non-Patent Citations (2)
| Title |
|---|
| CHOI, N. H.等: "Effects of neolignans from the stem bark of Magnolia obovata on plant pathogenic fungi", 《JOURNAL OF APPLIED MICROBIOLOGY》 * |
| 杨春等: "Obovatol及其衍生物:合成及药用活性研究概况", 《中国药物化学杂志》 * |
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