CN109369594A - A kind of myricetin derivative, preparation method and the usage containing ferulic amide - Google Patents
A kind of myricetin derivative, preparation method and the usage containing ferulic amide Download PDFInfo
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- CN109369594A CN109369594A CN201811476191.3A CN201811476191A CN109369594A CN 109369594 A CN109369594 A CN 109369594A CN 201811476191 A CN201811476191 A CN 201811476191A CN 109369594 A CN109369594 A CN 109369594A
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Abstract
The invention discloses a kind of myricetin derivative, preparation method and the usage containing ferulic amide, general structure are as follows: where R is alkoxy, halogen atom, hydrogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom.The substituted-phenyl is alkoxy, halogen atom, hydrogen atom and nitro o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon atom on phenyl ring.The present invention is resistant to tobacco mosaic virus disease, tobacco ralstonia solanacearum, citrus processing and rice leaf spot bacteria.
Description
Technical field
The present invention relates to chemical technology field, a kind of myricetin derivative containing ferulic amide, same is related in particular to
When further relate to the myricetin derivative containing ferulic amide preparation method and this contain the myricetin derivative of ferulic amide
Application in Antiphytoviral and in terms of inhibiting phytopathogen.
Background technique
Myricetin different name myricetin, myricetin belong to flavonoid drugs, are widely present in various plants,
Abundance.(He Guixia, Pei Gang, the Yao nationality wait National medicine magazine, 2000,6,40-41.) such as what osmanthus rosy clouds in 2000 from
It is isolated in the stem of vine tea.It is antitumor, antibacterial, antiviral, anti-oxidant and anti-inflammatory etc. raw that pharmacological research shows that myricetin has
Object activity.
2011, equal (when Zhang Lijing, Wang Ming modest treasure's traditional Chinese medical science traditional Chinese medicines, 2011,1,31.) used Murine Model of Intraperitoneal Infection mould
Type, protection of the observation myricetin to the infection test mice of staphylococcus aureus, streptococcus pneumonia, A type hemolytic streptococcus
Effect；Rat granuloma model, prevention effect of the observation myricetin to it are caused using xylene-induced ear swelling in mice and agar.It grinds
Study carefully the result shows that: myricetin in Mice Body have good antibacterial and anti-inflammatory activity.
2014, (Nguyen, T.H.V., Trinh, A.V., Nguyen, X.N., et al. natural products were logical by Nguyen etc.
Interrogate, 2014,9,643-645.) myricetin has been isolated from Vermilion by chromatography combined method, and have studied myricetin pair
The effect of Coxsackie virus, the study found that IC of the myricetin to the virus50Value is 40.1 μM, and it is anti-to illustrate that myricetin has
Virus activity.
2014, Zhao (synthesis of Zhao Hong chrysanthemum myricetin derivative and bioactivity research [D] Guizhou University, 2014) report
A series of myricetin of class containing the Heterocyclylalkyl derivatives in road test synthesized compound to breast cancer cell using colorimetric method
The in-vitro multiplication inhibitory activity of MDA-MB-231, wherein when concentration is 1 μm of ol/L, the inhibitory activity of part of compounds is high
In comparison medicine Gefitinib (9.73 ± 8.04%).
2015, and Xue (Europe Xue, W., Song, B.A., Zhao, H.J., et al. pharmaceutical chemistry, 2015,97,155-
163.) a series of myricetin of class containing acylhydrazone derivatives are reported.Using colorimetric method, mankind's cream has been carried out to synthesized compound
The in-vitro multiplication inhibitory activity of adenocarcinoma cell MDA-MB-231 is tested, and result of study shows: myricetin acylhydrazone is to people
Class breast cancer cell MDA-MB-231 shows preferable inhibiting rate.
2017, Xiao's (Xiao Wei, Ruan Xianghui, Li Qin, wait Chemical Journal of Chinese Universities, 2017,38,35-40.) reported
A series of amides myricetin derivatives, and test to rice leaf spot bacteria, citrus processing and tobacco ralstonia solanacearum
Inhibitory activity, test result shows: such compound has certain inhibitory activity to 3 kinds of bacteriums for test.
2017, clock (center Zhong, X.M., Wang, X.B., Chen, L.J., et al. chemistry, 2017,106.) etc.
A series of compounds for containing 1,3,4- thiadiazoles structures have been synthesized, anti-cigarette is carried out to synthesized compound using half leaf withered spot method
The determination of activity of showy flowers of herbaceous plants mosaic virus.Preliminary test result shows: under 500 μ g/mL concentration, in terms of therapeutic activity, and part
EC of the compound to tobacco mosaic virus (TMV)50Value is better than Ningnanmycin.Under 100 μ g/mL concentration, part of compounds is to the white leaf of rice
The EC of the bacteriostatic activity of blight50Value is better than commercial References medicine Thiodiazole-copper.
In conclusion myricetin is more in the research of field of medicaments, but had not been reported in the research of pesticide field.
Summary of the invention
Present invention aims to overcome that disadvantages mentioned above and provide a kind of resisting tobacco mosaic virus disease, tobacco ralstonia solanacearum,
The myricetin derivative containing ferulic amide of citrus processing and rice leaf spot bacteria.
The preparation method of another object of the present invention is to provide this myricetin derivative containing ferulic amide.
A further object of the present invention is to provide the myricetin derivatives containing ferulic amide in Antiphytoviral and inhibition
Application in terms of phytopathogen.
The technical scheme is that a kind of myricetin derivative containing ferulic amide, general structure are as follows:
Wherein, R is alkoxy, halogen atom, hydrogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom.
The substituted-phenyl is alkane o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon atom on phenyl ring
Oxygroup, halogen atom, hydrogen atom and nitro.
A kind of preparation method of myricetin derivative containing ferulic amide of the invention, the specific steps are as follows: (1) with Ah
Wei's acid is raw material, and 4- hydroxyls are protected with acetic anhydride, obtain intermediate 1:
(2) using intermediate 1, substitution substituted aniline as raw material, with 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimine
Hydrochloride, I-hydroxybenzotriazole are catalyst, using acetonitrile as solvent, prepare (E) -3 (4- hydroxy 3-methoxybenzene base)-N-
(substituted-phenyl) acrylamide (intermediate 2):
(3) it using myricetrin, iodomethane and dibromo alkyl as raw material, using potassium carbonate as catalyst, prepares 3- (bromine alkyl)-
3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 3):
(4) with 3- (bromine alkyl) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 3) and (E) -3 (4- hydroxyl -3-
Methoxyphenyl)-N- (substituted-phenyl) acrylamide (intermediate 2) be raw material, be catalyst, N, N- dimethyl methyl with potassium carbonate
Amide is that solvent prepares (target compound 4), as follows:
Myricetin derivative containing ferulic amide of the invention is used to prepare resisting tobacco mosaic virus disease, citrus bacterial canker disease
Application in terms of bacterium, rice leaf spot bacteria and tobacco ralstonia solanacearum pesticide and disinfectant use in agriculture.
Compared with prior art, the present invention having apparent beneficial effect, as can be known from the above technical solutions: the present invention is with poplar
Antimellin, iodomethane, ferulic acid, substituted aniline, dibromo alkyl prepare the myricetin derivative containing ferulic amide, will have excellent
Active ferulic amide group is introduced into the structure of myricetin, and it is derivative to have synthesized a series of myricetins containing ferulic amide
Object by the Antiphytoviral to the synthesized myricetin derivative containing ferulic amide and presses down phytopathogen active testing,
It was found that the compound of the present invention has preferable Antiphytoviral (tobacco mosaic virus (TMV)) activity and excellent suppression phytopathogen (tobacco
Ralstonia solanacearum, citrus processing and rice leaf spot bacteria) activity, it can be used for preparing Antiphytoviral pesticide and prepare agricultural
Fungicide.
Specific embodiment
Embodiment 1
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl) and-N- (p-methylphenyl) acrylamide (target compound 4a) preparation method, including
Following steps: (1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Ferulic acid 15.45mmol is added into round-bottomed flask, is dissolved with 10% sodium hydroxide solution 40mL, then
The acetic anhydride of 19.31mmol is added, after stirring 1h under normal temperature condition, pours into 200mL water, pH is adjusted to acidity, filtering to get
To intermediate 1.
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methylphenyl) acrylamide
2.33mmol (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid, 1- are added into 100mL round-bottomed flask
Hydroxybenzotriazole 2.79mmol and 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate 2.79mmol, with
30mL acetonitrile dissolves them, after stirring 3h under room temperature, is slowly added dropwise the acetonitrile that 20mL contains 2.79mmol open-chain crown ether, and 90
Flow back 3-5h under the conditions of DEG C, after ethyl acetate extraction, is spin-dried for solvent, and 30mL acetonitrile is added again and 4.66mmol 80% is hydrated
Hydrazine, after stirring at normal temperature 1h, to entering in 200mL water, with 5% salt acid for adjusting pH to acidity, filtering obtains intermediate 2.
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Sequentially added in 250mL round-bottomed flask 4.64g myricetrin (10mmol), 22.09g potassium carbonate (16mmol) and
7.50mL iodomethane (120mmol), room temperature is slowly added dropwise after stirring 0.5-1h under room temperature in 120mL n,N-Dimethylformamide
Stir 48h, thin-layer chromatography tracking reaction (methanol: ethyl acetate=1:4, V/V).After stopping reaction, filtering precipitating, filter residue second
Acetoacetic ester (or methylene chloride) washing, merging filtrate are diluted with 100mL water, three times with ethyl acetate (or methylene chloride) extraction,
Merge organic layer, be concentrated under reduced pressure, then concentrate is dissolved in 30mL dehydrated alcohol, is warming up to reflux, after solution clarification, returns
It flows down and 16mL concentrated hydrochloric acid is added, then there is yellow solid precipitation, the reaction was continued 2h is cooling, and filtering obtains crude product 3- hydroxyl-
3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin.Crude product 1.29mmol is added in 30mL n,N-Dimethylformamide, and carbon is added
Sour potassium 3.86mmol and dibromopropane 3.86mmol after ambient temperature overnight, is poured into 200mL water, is filtered, recrystallizing methanol.(4)
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup) third oxygen
Base) -3- methoxyphenyl)-N- (p-methylphenyl) acrylamide amine preparation
(E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methylphenyl) acryloyl is added into 100mL round-bottomed flask
Amine 0.981mmol, potassium carbonate 2.94mmol, n,N-Dimethylformamide 30mL stir 1h under room temperature, and addition contains 1.08mmol
(E) the n,N-Dimethylformamide 20mL of -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methylphenyl) acrylamides, 105 DEG C
Under the conditions of react 5-7h, pour into 200mL water, filter, recrystallizing methanol after cooling.
Embodiment 2
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (p-methoxyphenyl) acrylamide (target compound 4b) preparation method, packet
Include following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using P-nethoxyaniline as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, (4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxies
Phenyl) -4H- chromene -3- base) oxygroup) propoxyl group) -3- methoxyphenyl) and-N- (p-methoxyphenyl) acrylamide preparation
Such as 1 (4) step of embodiment.Difference is with (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl)
Acrylamide is raw material.
Embodiment 3
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (p-methylphenyl) acrylamide (target compound 4c) preparation method, including
Following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methylphenyl) acrylamide
Such as 1 (2) step of embodiment,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (p-methylphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, difference is being original with -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin of 3- (4- bromobutane)
Material.
Embodiment 4
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (p-methoxyphenyl) acrylamide (target compound 4d) preparation method, packet
Include following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using P-nethoxyaniline as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (p-methoxyphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, difference with 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin and
(E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl) acrylamides are raw material.
Embodiment 5
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide (target compound 4e) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using to m-chloroaniline as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acryloyl
Amine is raw material.
Embodiment 6
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide (target compound 4f) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using to m-chloroaniline as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acryloyl
Amine and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 7
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (rubigan) acrylamide (target compound 4g) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acrylamide
Such as 1 (2) step of embodiment, difference using parachloroanilinum as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (rubigan) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acryloyl
Amine is raw material.
Embodiment 8
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (rubigan) acrylamide (target compound 4h) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acrylamide
Such as 1 (2) step of embodiment, difference using parachloroanilinum as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (rubigan) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acryloyl
Amine and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 9
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (phenyl) acrylamide (target compound 4i) preparation method, including following step
It is rapid:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (phenyl) acrylamide
Such as 1 (2) step of embodiment, difference using aniline as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (phenyl) acrylamide preparation
Such as 1 (4) step of embodiment, difference in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (phenyl) acrylamide and
3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 10
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (phenyl) acrylamide (target compound 4j) preparation method, including following step
It is rapid:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (phenyl) acrylamide
Such as 1 (2) step of embodiment, difference using aniline as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (phenyl) acrylamide preparation
Such as 1 (4) step of embodiment, difference is in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (phenyl) acrylamide
Raw material.
Embodiment 11
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (3,4- 3,5-dimethylphenyl) acrylamide (target compound 4k) preparation method,
The following steps are included:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- 3,5-dimethylphenyl) acrylamide
Such as 1 (2) step of embodiment, difference with 3,4- dimethylaniline for raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (3,4- 3,5-dimethylphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- 3,5-dimethylphenyl)
Acrylamide is raw material.
Embodiment 12
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (3,4- 3,5-dimethylphenyl) acrylamide (target compound 4l) preparation method,
The following steps are included:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- 3,5-dimethylphenyl) acrylamide
Such as 1 (2) step of embodiment, difference with 3,4- dimethylaniline for raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (3,4- 3,5-dimethylphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- 3,5-dimethylphenyl)
Acrylamide and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 13
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl) the preparation side-N- (3,4- Dimethoxyphenyl) acrylamide (target compound 4m)
Method, comprising the following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- Dimethoxyphenyl) acrylamide
Such as 1 (2) step of embodiment, difference with 3,4- dimethoxyaniline for raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (3,4- Dimethoxyphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dimethoxy benzenes
Base) acrylamide be raw material.
Embodiment 14
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl) the preparation side-N- (3,4- Dimethoxyphenyl) acrylamide (target compound 4n)
Method, comprising the following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- Dimethoxyphenyl) acrylamide
Such as 1 (2) step of embodiment, difference with 3,4- dimethoxyaniline for raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference is sub using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (3,4- Dimethoxyphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dimethoxy benzenes
Base) acrylamide and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin is raw material.
Embodiment 15
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (p-bromophenyl) acrylamide (target compound 4o) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-bromophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using para-bromoaniline as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (p-bromophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-bromophenyl) acryloyl
Amine is raw material.
Embodiment 16
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (p-bromophenyl) acrylamide (target compound 4p) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-bromophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using para-bromoaniline as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (p-bromophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-bromophenyl) acryloyl
Amine and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 17
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (3,4- dichlorophenyl) acrylamide (target compound 4q) preparation method, packet
Include following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dichlorophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using 3,4-DCA as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (3,4- dichlorophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dichlorophenyl) third
Acrylamide is raw material.
Embodiment 18
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (3,4- dichlorophenyl) acrylamide (target compound 4r) preparation method, packet
Include following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dichlorophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using 3,4-DCA as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (3,4- dichlorophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (3,4- dichlorophenyl) third
Acrylamide and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 19
(E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) amoxy) -3- methoxyphenyl)-N- (rubigan) acrylamide (target compound 4s) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acrylamide
Such as 1 (2) step of embodiment, difference using parachloroanilinum as raw material,
(3) 3- (5- bromo pentane silane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromo pentane as raw material,
(4) (E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) amoxy) -3- methoxyphenyl)-N- (rubigan) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (rubigan) acryloyl
Amine and 3- (5- bromo pentane silane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 20
(E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) amoxy) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide (target compound 4t) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using m-chloroaniline as raw material,
(3) 3- (5- bromo pentane silane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromo pentane as raw material,
(4) (E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) amoxy) -3- methoxyphenyl)-N- (chlorphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (chlorphenyl) acryloyl
Amine and 3- (5- bromo pentane silane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 21
(E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) amoxy) -3- methoxyphenyl)-N- (p-methoxyphenyl) acrylamide (target compound 4u) preparation method, packet
Include following steps:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl) acrylamide
Such as 1 (2) step of embodiment, difference using P-nethoxyaniline as raw material,
(3) 3- (5- bromo pentane silane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromo pentane as raw material,
(4) (E) -3- (4- (5- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) amoxy) -3- methoxyphenyl)-N- (p-methoxyphenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (p-methoxyphenyl) third
Acrylamide and 3- (5- bromo pentane silane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
Embodiment 22
(E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) propoxyl group) -3- methoxyphenyl)-N- (o-fluorophenyl) acrylamide (target compound 4v) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (o-fluorophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using adjacent fluoroaniline as raw material,
(3) 3- (3- N-Propyl Bromide) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment,
(4) (E) -3- (4- (3- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) propoxyl group) -3- methoxyphenyl)-N- (o-fluorophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (o-fluorophenyl) acryloyl
Amine is raw material.
Embodiment 23
(E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base)
Oxygroup) butoxy) -3- methoxyphenyl)-N- (o-fluorophenyl) acrylamide (target compound 4w) preparation method, including with
Lower step:
(1) preparation of (E)-3 (4- acetoxy-3-methoxyphenyl) acrylic acid
Such as 1 (1) step of embodiment,
(2) preparation of (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (o-fluorophenyl) acrylamide
Such as 1 (2) step of embodiment, difference using adjacent fluoroaniline as raw material,
(3) 3- (4- bromobutane) -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment, difference using dibromobutane as raw material,
(4) (E) -3- (4- (4- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3-
Base) oxygroup) butoxy) -3- methoxyphenyl)-N- (o-fluorophenyl) acrylamide preparation
Such as 1 (4) step of embodiment, distinguish in (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (o-fluorophenyl) acryloyl
Amine and 3- (4- bromobutane) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin are raw material.
The physicochemical property and mass spectrometric data of the myricetin derivative of synthesized amide containing oxadiazoles are shown in Table 1, hydrogen nuclear magnetic resonance
Spectrum (1H NMR) and carbon spectrum (13C NMR) data are shown in Table 2.
1 target compound physicochemical property of table
2 target compound nuclear magnetic resonance modal data of table
The test of 1 target compound activity of resisting tobacco mosaic virus of test example
(1) test method
A. Virus purification
Quadratic method (Zhou, X.P. are avenged using week；Xu,Z.X.；Xu,J.；Li,D.B.J.South
Chin.Agric.Univ.1995,16,74-79.), inoculation 3 weeks or more are chosen, tobacco mosaic virus (TMV) systemic infection host's lobus cardiacus
Cigarette plant upper blade, is homogenized in phosphate buffer, double gauze filtering, and 8000g centrifugation is handled through 2 polyethylene glycol, then
Centrifugation, precipitating phosphate buffer suspend to get the refining liquid body of tobacco mosaic virus (TMV) is arrived.Entire experiment carries out at 4 DEG C.With
Ultraviolet specrophotometer measures the absorbance value of 260nm wavelength, calculates virus concentration according to formula.
Virus concentration (mg/mL)=(A260× extension rate)/E0.1% 1cm 260nm
Wherein E indicates extinction coefficient, i.e. when wavelength 260nm, concentration is the suspension of 0.1% (1mg/mL), is in light path
Absorbance value when 1cm.The E of tobacco mosaic virus (TMV)0.1% 1cm 260nmIt is 5.0.
B. the living body therapeutic effect that medicament infects tobacco mosaic virus (TMV): taking one plant of Nicotiana glutinosa, is trimmed and retains 3-5 piece
Tobacco leaf equably sprinkles diamond dust on every leaf, dips tobacco mosaic virus disease poison (500 μ g/mL) with spread pen, equably
Brush on tobacco leaf waits for tobacco leaf on virus inoculation (0.5-1h), washes away diamond dust with clear water, after natural drying, dips mesh with writing brush
Mark compound solvent (500mg/mL) is equably applied to half leaf of the right side of tobacco leaf.After drying, moisturizing under the conditions of moving it to 28 DEG C
Culture.After 2-3d, there is apparent spot in blade, records the spot number of the right and left, brings formula into and calculate its inhibiting rate.Each
Compound carries out 2-3 times in parallel.The living body protective effect that medicament infects tobacco mosaic virus (TMV).
C. the living body protective effect that medicament infects tobacco mosaic virus (TMV): taking one plant of Nicotiana glutinosa, is trimmed and retains 3-5 piece
Tobacco leaf dips half leaf of the right side that target compound solvent (500mg/mL) is equably applied to tobacco leaf with writing brush.After 12h, by Buddha's warrior attendant
Sand is equably sprinkling upon the right and left of blade, dips tobacco mosaic virus disease poison (500 μ g/mL) with spread pen, uniform scrubbing brush is in cigarette
Ye Shang.To tobacco leaf on virus inoculation (0.5-1h), diamond dust is washed away with clear water, after natural drying, moisturizing under the conditions of moving to 28 DEG C
Culture.After 2-3d, there is apparent spot in blade, records the spot number of the right and left, and bringing formula into, to calculate its inhibiting rate each
Compound carries out 2-3 times in parallel.
D. the inhibiting rate of resisting tobacco mosaic virus observes blade after calculating 2-3d, when occurring obvious withered spot on blade, with same
Leaf half leaf of a left side is compareed as blank control, Ningnanmycin as medicament, records every blade or so spot number, and following formula calculates
The inhibiting rate of its activity of resisting tobacco mosaic virus.
I=(L-R)/L × 100%
Wherein, I is the inhibiting rate of target compound activity of resisting tobacco mosaic virus；L is the withered spot number of left half leaf, and R is the right side
The withered spot number of half leaf.
(2) the biological activity test result of resisting tobacco mosaic virus
Treatment of 3 target compound of table to tobacco mosaic virus (TMV), protection activitya
aAverage test is three times.bFirst conductor compound.cThe inhibitory activity of commodity medicament Ningnanmycin is positive control.
It is control with commodity medicament Ningnanmycin using half leaf withered spot method, when for examination concentration being 500 μ g/mL, tests mesh
Compound 4a-4w is marked to the treatment of tobacco mosaic virus (TMV) and protection activity (being shown in Table 3).The test result shows: partial target
Closing object has treatment and protection activity to tobacco mosaic virus (TMV).The activity of resisting tobacco mosaic virus test result such as table of target compound
Shown in 3, majority of compounds all has certain inhibitory activity to tobacco mosaic virus disease poison.Wherein, in terms for the treatment of, chemical combination
The inhibiting rate of object 4o is 50.55%, close to the therapeutic activity 51.21% of Ningnanmycin, in terms of protection, compound 4e, 4f, 4m
Inhibiting rate with 4q is respectively 51.66,52.39,62.09 and 58.16%, near or above the protection activity of Ningnanmycin
55.71%.
The anti-vegetative bacteria active testing of 2 target compound of test example
(1) test method
Using nephelometry, target compound is tested to citrus processing, rice leaf spot bacteria and tobacco bacterial wilt
The inhibitory activity of bacterium, specific steps are as follows:
A. in 2000mL beaker be added 1000mL sterile purified water, sequentially added under electromagnetic agitation peptone 5.0g,
Yeast powder 1.0g, glucose 10.0g, beef extract 3.0g, it is to be mixed uniformly after pH adjusted to neutrality with sodium hydrate aqueous solution
(7.2±0.2)；
B. test tube is cleaned sterilizing to be placed on rack for test tube, is pipetted into every test tube in the first step (1) using liquid-transfering gun
After solution 4.0mL plus rubber stopper, every 6 test tubes packaging are once, stand-by after 121 DEG C of sterilizing 20min using autoclave；
C. 0.00375-0.0042g test compound sample is weighed in centrifuge tube, after 150 μ L dmso solutions
It pipettes after 80 μ L and 40 μ L to sterilizing respectively in numbered centrifuge tube, separately adds 40 μ L dimethyl sulfoxides to equipped with 40 μ L samples
4mL Tween-20 is respectively added into above-mentioned centrifuge tube for the centrifuge tube of solution, while Yekuzuo compares medicament, and dimethyl sulfoxide is made
Blank control；
D. solution pipettes in 1mL to 3 dress second step (2) and (operates before alcolhol burner in test tube, prevent it in every centrifuge tube
Its germ contamination)；
E. 96 orifice plate of blank is taken, blank OD value is surveyed and excludes the hole that OD value is greater than 0.05, to be added 200 in backward each available hole
In μ L (4) in test tube solution survey citrus processing OD value and recorded, after 40 μ L activation is finally accessed into every test tube or
Tobacco ralstonia solanacearum or rice leaf spot bacteria strain wrap the shaken cultivation 24- in 30 DEG C, 180rpm constant-temperature table with newspaper
48h, during which solution O D value takes 200 μ L solution to survey in test tube to track Bacteria cold shock, after culture in test tube
OD value simultaneously records；
F. compound is as follows to Bacteria suppression rate calculation formula,
Correct OD value=value of OD containing bacterium culture medium-aseptic culture medium OD value
(2) the biological activity test result of anti-plant pathogen
4 target compound of table is set under concentration respectively to the inhibiting rate of three kinds of bacteriumsa
aAverage test three timesbFirst conductor compound.cUsing the inhibitory activity of commodity Yekuzuo as positive control.
Using nephelometry, using commodity medicament Yekuzuo as positive control, when being 100,50 μ g/mL for examination concentration, test
Inhibitory activity (be shown in Table 4) of the target compound to citrus processing, tobacco ralstonia solanacearum and rice leaf spot bacteria.The survey
Test result shows: all compounds all have certain inhibiting rate to vegetative bacteria for test.Wherein, when concentration is 100 μ g/
ML, compound 4b, 4d, 4e, 4f, 4g, 4i, 4j, 4k, 4m, 4n and 4o are more than or approach to the inhibiting rate of citrus processing
Yekuzuo (63.33%)；Compound 4c, 4d and 4g are more than Yekuzuo (56.07%) to the inhibiting rate of rice leaf spot bacteria.
When concentration is 50 μ g/mL, compound 4a, 4b, 4d, 4j are more than Yekuzuo (41.55%) to the inhibiting rate of citrus processing；
Compound 4c, 4f, 4j and 4q are more than Yekuzuo (33.80%) to the inhibiting rate of rice leaf spot bacteria.
Assay activity as above statistics indicate that the myricetin derivative containing ferulic amide to tobacco mosaic virus (TMV) and phytopathy
Bacterium (hundred leaf spoting bacteria of citrus processing, tobacco ralstonia solanacearum and rice) has certain inhibiting effect, part of target
Compound is presented with excellent inhibitory activity to plant virus and phytopathogen, can be used as potential Antiphytoviral drug, has
The prospect preferably applied.
Synthesis is as described above, be only presently preferred embodiments of the present invention, not to the limit of the invention made in any form
System, it is any without departing from technical solution of the present invention content, according to the technical essence of the invention any letter to the above embodiments
Single modification, equivalent variations and modification, all of which are still within the scope of the technical scheme of the invention.
Claims (3)
1. a kind of myricetin derivative containing ferulic amide, general structure are as follows:
Wherein, R is alkoxy, halogen atom, hydrogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom；
The substituted-phenyl be phenyl ring on it is o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon
Alkoxy, halogen atom, hydrogen atom and the nitro of atom.
2. a kind of preparation method of the myricetin derivative containing ferulic amide, the specific steps are as follows:
(1) using ferulic acid as raw material, the hydroxyl of 4-positions is protected with acetic anhydride, obtains intermediate 1:
(2) using intermediate 1, substitution substituted aniline as raw material, with 1- ethyl-(3- dimethylaminopropyl) phosphinylidyne diimine hydrochloric acid
Salt, I-hydroxybenzotriazole are catalyst, and using acetonitrile as solvent, preparation (E) -3 (4- hydroxy 3-methoxybenzene base)-N- (replaces
Phenyl) acrylamide (intermediate 2):
；
(3) using myricetrin, iodomethane and dibromo alkyl as raw material, using potassium carbonate as catalyst, 3- (bromine alkyl) -3 ', 4 ' is prepared,
5 ', 5,7- pentamethoxyl myricetin (intermediate 3):
；
(4) with 3- (bromine alkyl) -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 3) and (E) -3 (4- hydroxyl -3- first
Phenyl)-N- (substituted-phenyl) acrylamide (intermediate 2) be raw material, be catalyst, N, N- dimethyl methyl with potassium carbonate
Amide is that solvent prepares (target compound 4), as follows:
。
3. a kind of myricetin derivative containing ferulic amide is used to prepare resisting tobacco mosaic virus disease, citrus processing, water
Application in terms of rice bacterial leaf spot pathogenic bacteria and tobacco ralstonia solanacearum pesticide and disinfectant use in agriculture.
Priority Applications (1)
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| CN113801022A (en) * | 2021-07-23 | 2021-12-17 | 贵州大学 | Ferulic acid eugenol and isoeugenol heterozygote and application thereof |
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| CN112194654A (en) * | 2020-08-28 | 2021-01-08 | 贵州大学 | Benzimidazolium-containing myricetin derivative, preparation method and application |
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| CN113233993B (en) * | 2021-05-18 | 2022-07-01 | 贵州大学 | Ferulic acid amide derivative and synthetic method thereof |
| CN113801022A (en) * | 2021-07-23 | 2021-12-17 | 贵州大学 | Ferulic acid eugenol and isoeugenol heterozygote and application thereof |
| CN113801022B (en) * | 2021-07-23 | 2023-07-28 | 贵州大学 | Eugenol ferulate and isoeugenol hybrid and application thereof |
| CN114195691A (en) * | 2021-12-16 | 2022-03-18 | 贵州大学 | Amide-containing ferulic acid derivative and preparation method and application thereof |
| CN114195691B (en) * | 2021-12-16 | 2023-10-20 | 贵州大学 | Ferulic acid derivative containing amide and preparation method and application thereof |
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