CN109438433A - A kind of myricetin derivative, the preparation method and the usage of amide containing oxadiazoles - Google Patents
A kind of myricetin derivative, the preparation method and the usage of amide containing oxadiazoles Download PDFInfo
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—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
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Abstract
The invention discloses myricetin derivative, the preparation method and the usage of a kind of amide containing oxadiazoles, general formula (A) is as follows, in which: R is alkoxy, halogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom.The substituted-phenyl is alkoxy, halogen and nitro o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon atom on phenyl ring.Resisting tobacco mosaic virus disease, citrus processing and rice leaf spot bacteria of the present invention.
Description
Technical field
The present invention relates to chemical technology field, a kind of myricetin derivative, same of amide containing oxadiazoles is related in particular to
When further relate to the amide containing oxadiazoles myricetin derivative preparation method and the amide containing oxadiazoles myricetin derivative
Application in Antiphytoviral and in terms of inhibiting phytopathogen.
Background technique
Myricetin different name myricetin, myricetin, myricetin belong to flavonoid drugs, are widely present in a variety of
In plant, abundance.2000 Nian Hegui rosy clouds etc. (He Guixia, Pei Gang, the Yao nationality, wait National medicine magazine, and 2000,6,
It is 40-41.) isolated from the stem of vine tea.It is antitumor, antibacterial, antiviral, anti-oxidant that pharmacological research shows that myricetin has
With the bioactivity such as anti-inflammatory, there is certain research and application value.But majority is limited to medical research, in terms of pesticide research compared with
It is few.
2011, equal (when Zhang Lijing, Wang Mingqian 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., the et al.Natural such as Nguyen
Product Communications, 2014,9,643-645.) red bayberry isolated from Vermilion by chromatography combined method
Element, and effect of the myricetin to Coxsackie virus is had studied, the study found that IC of the myricetin to the virus50Value is 40.1 μ
Mol/L illustrates that myricetin has antiviral activity.
2014, Zhao (synthesis of Zhao Hongju 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%), when concentration is 10 μm of ol/L, close pair of the inhibitory activity of part of compounds
According to medicine Gefitinib (67.52 ± 4.14%).
2015, Xue (Xue, W., Song, B.A., Zhao, H.J.Eur.J.Med.Chem., 2015,97,155-163.)
Report a series of myricetin of class containing acylhydrazone derivatives, using myricetrin as raw material, iodomethane protect hydroxyl, successively with bromoacetic acid second
Ester, hydrazine hydrate, the fragrant formaldehyde reaction that difference replaces are final to synthesize myricetin acylhydrazone.Using colorimetric method, to being closed
At compound carried out the in-vitro multiplication inhibitory activity test of mankind mastopathy cell MDA-MB-231, result of study shows:
Myricetin acylhydrazone all shows preferable inhibiting rate to mankind mastopathy cell MDA-MB-231.
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 (Zhong, X.M., Wang, X.B., Chen, L.J., et al.Chem.Cent.J., 2017,
Etc. 106.) a series of compounds for containing 1,3,4- thiadiazoles structures have been synthesized, using half leaf withered spot method to synthesized compound
Carry out the determination of activity of resisting tobacco mosaic virus.Preliminary test result shows: under 500 μ g/mL concentration, in therapeutic activity side
Face, better than 211.1 μ g/mL of Ningnanmycin.Under 100 μ g/mL concentration, commodity are better than to the bacteriostatic activity of bacterial blight of rice
94.9 μ g/mL of comparison medicine Thiodiazole-copper.
In conclusion myricetin has preferable antiviral activity and bacteriostatic activity in terms of medical research, but in pesticide
The application study of aspect obtains less, and forefathers' majority concentrates on the bioactivity research to myricetin itself, and to myricetin
It is relatively fewer to carry out structural modification.
Summary of the invention
Present invention aims to overcome that disadvantages mentioned above and provide a kind of resisting tobacco mosaic virus disease, citrus processing and
The myricetin derivative of the amide containing oxadiazoles of rice leaf spot bacteria.
Another object of the present invention is to provide the preparation methods of the myricetin derivative of the amide containing oxadiazoles.
A further object of the present invention is to provide the myricetin derivatives of amide containing oxadiazoles in Antiphytoviral and inhibition
Application in terms of phytopathogen.
A kind of myricetin derivative of amide containing oxadiazoles of the invention, general structure (A) are as follows:
Wherein, R is alkoxy, halogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom.Described takes
It is alkoxy, halogen o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon atom on phenyl ring for phenyl
And nitro.
A kind of preparation method of the myricetin derivative of amide containing oxadiazoles of the invention, comprises the following steps that
(1) using semicarbazide hydrochloride, substituted benzaldehyde as raw material, using elemental iodine as oxidant, with methanol, water and Isosorbide-5-Nitrae-
Dioxane is solvent, prepares 2- amino -5- substituted-phenyl -1,3,4- oxadiazoles (intermediate 1):
(2) with 2- amino -5- substituted-phenyl -1,3,4- oxadiazoles (intermediate 1) and chloracetyl chloride are raw material, with potassium carbonate
Make solvent for catalyst, with n,N-Dimethylformamide and methylene chloride, (5- phenyl substituent -1,3,4- are disliked the preparation chloro- N- of 2-
Diazole)-acetamide (intermediate 2):
(3) using myricetrin and iodomethane as raw material, using potassium carbonate as catalyst, acidity, which is adjusted, prepares 3- hydroxyl -3 ', and 4 ',
5 ', 5,7- pentamethoxyl myricetin (intermediate 3):
(4) with 3- hydroxyl -3 ', (5- phenyl replaces by 4 ', 5 ', 5,7- pentamethoxyl myricetin (intermediate 3) and the chloro- N- of 2-
Base -1,3,4- oxadiazoles)-acetamide (intermediate 2) is raw material, it is catalyst with potassium carbonate, n,N-Dimethylformamide is molten
Agent prepares 2-, and ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) (5- takes oxygroup-N-
For phenyl -1,3,4- oxadiazoles -2- base) acetamide (target compound 4):
The myricetin derivative of amide containing oxadiazoles of the invention is used to prepare resisting tobacco mosaic virus disease, citrus bacterial canker disease
Application in terms of bacterium and rice leaf spot bacteria 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, semicarbazide hydrochloride, elemental iodine, chloracetyl chloride prepare the myricetin derivative of amide containing oxadiazoles, the present invention
Amide oxadiazoles group with excellent activity is introduced into the structure of myricetin, a series of poplar of amide containing oxadiazoles has been synthesized
Syphilis derivative, it is living by the Antiphytoviral and suppression phytopathogen of the myricetin derivative to synthesized amide containing oxadiazoles
Property test, discovery the compound of the present invention has preferable Antiphytoviral (tobacco mosaic virus (TMV)) activity and excellent suppression phytopathy
Bacterium (hundred leaf spoting bacteria of citrus processing and rice) activity, can be used for preparing Antiphytoviral pesticide and prepares agricultural bactericidal
Agent.
Specific embodiment
Embodiment 1
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- (5-
Phenyl -1,3,4- oxadiazoles -2- base) acetamide (target compound 4a) preparation method, comprising the following steps:
(1) preparation of 2- amino-5-phenyl -1,3,4- oxadiazoles
Semicarbazide hydrochloride (9.42mmol), sodium acetate (9.42mmol) is added, into 100mL round-bottomed flask with 20mL bis-
Secondary water is dissolved, and the methanol 20mL containing benzaldehyde (9.42mmol) is then slowly added dropwise, stirs 20 minutes under normal temperature condition.
Solvent is spin-dried for, addition 40mL Isosorbide-5-Nitrae-dioxane, potassium carbonate (28.37mmol), elemental iodine (10.37mmol), 80~85 DEG C
Under the conditions of heat 4~6 hours, thin-layer chromatography tracking reaction is to no longer changing.Reactant is poured into 25% sodium thiosulfate water
In solution, it is spin-dried for, N, N- dimethyl methyl with methylene chloride: methanol=10:1 mixed extractant solvent with anhydrous sodium sulfate drying
Amide and recrystallize with dichloromethane obtain intermediate 1, yield 81%.
(2) preparation of the chloro- N- of 2- (5- phenyl -1,3,4- oxadiazoles)-acetamide
2- amino-5-phenyl -1,3,4- oxadiazoles (2.48mmol), potassium carbonate are added into 100mL round-bottomed flask
(7.45mmol) and 30mL n,N-Dimethylformamide, stirring at normal temperature to 2- amino-5-phenyl -1,3,4- oxadiazoles are complete
After dissolution, 15~20mL methylene chloride is added, stirring at normal temperature 0.5~1 hour, chloracetyl chloride is slowly added dropwise under condition of ice bath
(7.45mmol), reaction is overnight.After methylene chloride is spin-dried for, reactant is poured into ice water, obtains middle 2- chloro- N- (5- phenyl-
1,3,4- oxadiazoles)-acetamide, without purification, directly progress next step reaction.
(3) 3- hydroxyl -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) is slowly added dropwise after stirring 0.5~1 hour under room temperature in 120mL n,N-Dimethylformamide,
It is stirred at room temperature 48 hours, thin-layer chromatography tracking reaction (methanol: ethyl acetate=1:4).After stopping reaction, filtering precipitating, filter residue
It is washed with ethyl acetate (or methylene chloride), merging filtrate, is diluted with 100mL water, extracted with ethyl acetate (or methylene chloride)
Three times, merge organic layer, be concentrated under reduced pressure, then concentrate is dissolved in 30mL dehydrated alcohol, is warming up to reflux, clarified to solution
Afterwards, reflux is lower is added 16mL concentrated hydrochloric acid, then there is yellow solid precipitation, and the reaction was continued 2 hours, and cooling, filtering obtains crude product
3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetins, yield: 76%.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of (5- phenyl -1,3,4- oxadiazoles -2- base) acetamide
3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin (1.03mmol), carbonic acid are added into 50mL round-bottomed flask
Potassium (3.09mmol) and n,N-Dimethylformamide 20mL are slowly added dropwise 10mL and contain the chloro- N- of 2- after stirring 1 hour at 85 DEG C
The n,N-Dimethylformamide 10mL of (5- phenyl -1,3,4- oxadiazoles)-acetamide (1.04mmol) stirs 5~7 at 105 DEG C
Hour, thin-layer chromatography tracking reaction (reaction product shows fluorescence in the case where wavelength is the ultraviolet lamp of 365mm, solvent: ethyl acetate:
Methanol=15:1).Reactant is poured into 300mL water, the salt acid for adjusting pH of 6mol/L is added under stiring to acidity, has a large amount of
Solid is precipitated, and filters, and is rinsed 2~3 times with secondary water, and n,N-Dimethylformamide and recrystallizing methanol obtain target compound
4。
Embodiment 2
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- methyl) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4b) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- methyl)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using p-tolyl aldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- methyl) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- methyl)-phenyl) -1,3,4- oxadiazoles are original
Material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- methyl) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (5) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- methyl) phenyl) -1,3,4- oxadiazoles)-second
Amide is raw material.Yield is 40%, fusing point: 243.9-245.4 DEG C.
Embodiment 3
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- methoxyl group) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4c) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- methoxyl group)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using P-methoxybenzal-dehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- methoxyl group) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- methoxyl group)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- methoxyl group) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- methoxyl group) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 39%, fusing point: 252.6-253.9 DEG C.
Embodiment 4
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- tert-butyl) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4d) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- tert-butyl)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using p-t-Butylbenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- tert-butyl) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- tert-butyl)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- tert-butyl) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- tert-butyl) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 32%, fusing point: 241.3-242.2 DEG C.
Embodiment 5
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- chlorine) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4e) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- chlorine)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using p-chlorobenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- chlorine) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- chlorine)-phenyl) -1,3,4- oxadiazoles are raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- chlorine) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- chlorine) phenyl) -1,3,4- oxadiazoles)-acetyl
Amine is raw material.Yield is 35%, fusing point: 238.2-239.5 DEG C.
Embodiment 6
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(2- methoxyl group) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4f) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((2- methoxyl group)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using o-methoxybenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (2- methoxyl group) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((2- methoxyl group)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (2- methoxyl group) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (2- methoxyl group) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 45%, fusing point: 222.3-223.1 DEG C.
Embodiment 7
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(2,4- dimethoxy) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4g) preparation method, including following step
It is rapid:
(1) preparation of 2- amino -5- ((2,4- dimethoxy)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is with 2,4- dimethoxy benzaldehyde for raw material.
(2) prepared by the chloro- N- of 2- ((5- (2,4- dimethoxy) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is to dislike two with 2- amino -5- ((2,4- dimethoxy)-phenyl) -1,3,4-
Azoles is raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (2,4- dimethoxy) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is that ((5- (2,4- dimethoxy) phenyl) -1,3,4- dislikes two with the chloro- N- of 2-
Azoles)-acetamide be raw material.Yield is 43%, fusing point: 198.1-199.5 DEG C.
Embodiment 8
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- isopropyl) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4h) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- isopropyl)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 4- propylbenzyl aldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- isopropyl) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- isopropyl)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- isopropyl) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- isopropyl) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 43%, fusing point: 213.9-214.3 DEG C.
Embodiment 9
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(3,4- dimethyl) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4i) preparation method, including following step
It is rapid:
(1) preparation of 2- amino -5- ((3,4- dimethyl)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is with 3,4- dimethylbenzaldehyde for raw material.
(2) prepared by the chloro- N- of 2- ((5- (3,4- dimethyl) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is with 2- amino -5- ((3,4- dimethyl)-phenyl) -1,3,4- oxadiazoles
For raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (3,4- dimethyl) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is that ((5- (3,4- dimethyl) phenyl) -1,3,4- dislikes two with the chloro- N- of 2-
Azoles)-acetamide be raw material.Yield is 37%, fusing point: 203.4-213.8 DEG C.
Embodiment 10
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(3- methyl) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4j) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((3- methyl)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 3- tolyl aldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (3- methyl) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((3- methyl)-phenyl) -1,3,4- oxadiazoles are original
Material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (3- methyl) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (3- methyl) phenyl) -1,3,4- oxadiazoles)-second
Amide is raw material.Yield is 45%, fusing point: 196.6-197.7 DEG C.
Embodiment 11
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(3,4- dichloro) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4k) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((3,4- dichloro)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is with 3,4- dichlorobenzaldehyde for raw material.
(2) prepared by the chloro- N- of 2- ((5- (3,4- dichloro) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((3,4- dichloro)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (3,4- dichloro) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (3,4- dichloro) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 27%, fusing point: 220.1-220.3 DEG C.
Embodiment 12
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- bromine) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4l) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- bromine)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 4- bromobenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- bromine) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- bromine)-phenyl) -1,3,4- oxadiazoles are raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- bromine) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- bromine) phenyl) -1,3,4- oxadiazoles)-acetyl
Amine is raw material.Yield is 30%, fusing point: 243.1-247.7 DEG C.
Embodiment 13
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(2,4- dichloro) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4m) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((2,4- dichloro)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is with 2,4- dichlorobenzaldehyde for raw material.
(2) prepared by the chloro- N- of 2- ((5- (2,4- dichloro) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((2,4- dichloro)-phenyl) -1,3,4- oxadiazoles are
Raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (2,4- dichloro) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (2,4- dichloro) phenyl) -1,3,4- oxadiazoles) -
Acetamide is raw material.Yield is 24%, fusing point: 228.7-229.3 DEG C.
Embodiment 14
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(3,4- dimethoxy) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4n) preparation method, including following step
It is rapid:
(1) preparation of 2- amino -5- ((3,4- dimethoxy)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using Veratraldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (3,4- dimethoxy) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is to dislike two with 2- amino -5- ((3,4- dimethoxy)-phenyl) -1,3,4-
Azoles is raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (3,4- dimethoxy) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is that ((5- (3,4- dimethoxy) phenyl) -1,3,4- dislikes two with the chloro- N- of 2-
Azoles)-acetamide be raw material.Yield is 27%, fusing point: 247.3-237.7 DEG C.
Embodiment 15
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(3- bromine) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4o) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((3- bromine)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 3- bromobenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (3- bromine) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((3- bromine)-phenyl) -1,3,4- oxadiazoles are raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (3- bromine) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (3- bromine) phenyl) -1,3,4- oxadiazoles)-acetyl
Amine is raw material.Yield is 32%, fusing point: 224.3-224.7 DEG C.
Embodiment 16
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(2- bromine) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4p) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((2- bromine)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 2- bromobenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (2- bromine) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((2- bromine)-phenyl) -1,3,4- oxadiazoles are raw material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (2- bromine) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (2- bromine) phenyl) -1,3,4- oxadiazoles)-acetyl
Amine is raw material.Yield is 38%, fusing point: 209.9-210.3 DEG C.
Embodiment 17
2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N- ((5-
(4- nitro) phenyl) -1,3,4- oxadiazoles -2- bases) acetamide (target compound 4q) preparation method, comprising the following steps:
(1) preparation of 2- amino -5- ((4- nitro)-phenyl) -1,3,4- oxadiazoles
Such as 1 (1) step of embodiment, difference is using 4- nitrobenzaldehyde as raw material.
(2) prepared by the chloro- N- of 2- ((5- (4- nitro) phenyl) -1,3,4- oxadiazoles)-acetamide
Such as 1 (2) step of embodiment, difference is that, with 2- amino -5- ((4- nitro)-phenyl) -1,3,4- oxadiazoles are original
Material.
(3) 3- hydroxyl -3 ', the preparation of 4 ', 5 ', 5,7- pentamethoxyl myricetin
Such as 1 (3) step of embodiment.
(4) 2- ((5,7- dimethoxy-4 ' -one -2- (3,4,5- trimethoxyphenyl) -4H- chromene -3- base) oxygroup-N-
The preparation of ((5- (4- nitro) phenyl) -1,3,4- oxadiazoles -2- base) acetamide.
Such as 1 (4) step of embodiment, difference is with the chloro- N- of 2- ((5- (4- nitro) phenyl) -1,3,4- oxadiazoles)-second
Amide is raw material.Yield is 38%, fusing point: greater than 300 DEG C.
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
Test example 1: target compound activity of resisting tobacco mosaic virus test
(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 (0.5~1 hour), washes away diamond dust with clear water, after natural drying, is dipped in writing brush
Target compound solvent (500mg/mL) is taken equably to be applied to half leaf of the right side of tobacco leaf.After drying, move it under the conditions of 28 DEG C
Moisturizing culture.After 2~3 days, there is apparent spot in blade, records the spot number of the right and left, brings formula into and calculate its inhibition
Rate.Each compound carries out the living body protective effect that 2~3 medicaments infect tobacco mosaic virus (TMV) in parallel
C. the living body protective effect that medicament infects tobacco mosaic virus (TMV): taking one plant of Nicotiana glutinosa, is trimmed reservation 3~5
Piece tobacco leaf is dipped after target compound solvent (500mg/mL) is equably applied to half leaf of the right side .12 hours of tobacco leaf with writing brush, will
Diamond dust is equably sprinkling upon the right and left of blade, dips tobacco mosaic virus disease poison (500 μ g/mL), uniform scrubbing brush with spread pen
On tobacco leaf.To tobacco leaf on virus inoculation (0.5~1 hour), diamond dust is washed away with clear water, after natural drying, moves to 28 DEG C of items
Moisturizing culture under part, after 2~3 days, there is apparent spot in blade, records the spot number of the right and left, brings formula into and calculate it
The each compound of inhibiting rate carries out 2~3 times in parallel.
D. the inhibiting rate of resisting tobacco mosaic virus observes blade after calculating 2~3 days, when occurring obvious withered spot on blade, with
With left half leaf of leaf as blank control, Ningnanmycin is compareed as medicament, records every blade or so spot number, following formula meter
Calculate 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 Zuo Banye, 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 three timesbThe 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~4q is marked to the treatment of tobacco mosaic virus (TMV) and protection activity (being shown in Table 3).The test result shows: most of target
Compound has preferable treatment and protection activity to tobacco mosaic virus (TMV).The activity of resisting tobacco mosaic virus of target compound is surveyed
Test result is as shown in table 4, and majority of compounds all has certain inhibitory activity to tobacco mosaic virus (TMV) wherein, in treatment side
Face, the inhibiting rate of compound 4a, 4n and 4q are respectively 57.13%, 62.96% and 65.02%, living more than the treatment of Ningnanmycin
Property 51.21%, in terms of protection, the inhibiting rate of compound 4d, 4f and 4q are respectively 56.08%, 65.30% and 60.00%,
More than the protection activity 55.71%. of Ningnanmycin
The anti-vegetative bacteria active testing of 2 target compound of test example
(1) test method
Using nephelometry, target compound is tested to the inhibitory activity of citrus processing rice leaf spot bacteria, tool
Steps are as follows for gymnastics work:
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, with 150 μ L dmso solutions
It pipettes respectively after 80 μ L and 40 μ L to sterilizing afterwards in numbered centrifuge tube, separately adds 40 μ L dimethyl sulfoxides to equipped with 40 μ L samples
4mL Tween-20 is respectively added in Xiang Shangshu centrifuge tube in the centrifuge tube of product solution, while setting Thiodiazole-copper or Yekuzuo compares medicament,
Dimethyl sulfoxide makees 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 track Bacteria cold shock, after culture in test tube in test tube
It surveys OD value and 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 a of two kinds of bacteriums
aAverage test three timesbUsing 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
Target compound to the inhibitory activity of hundred leaf spoting bacteria of citrus processing and rice (is shown in Table 4.The test result shows: institute
Have compound that all there is certain inhibiting rate wherein to vegetative bacteria for test, when concentration be 100 μ g/mL, compound 4a,
4b, 4f, 4j are more than or close to Yekuzuo (63.33%) to the inhibiting rate of citrus processing；Compound 4c, 4f, 4j and 4q
Inhibiting rate to rice leaf spot bacteria is more than Yekuzuo (56.07%) when concentration is 50 μ g/mL, compound 4a, 4b, 4d,
4j is more than Yekuzuo (41.55%) to the inhibiting rate of citrus processing；Compound 4c, 4f, 4j and 4q are to rice bacterial leaf spot
The inhibiting rate of germ is more than Yekuzuo (33.80%)
Assay activity as above statistics indicate that the myricetin derivative containing oxadiazoles to tobacco mosaic virus (TMV) and phytopathogen (mandarin orange
Hundred leaf spoting bacteria of tangerine ulcer bacteria and rice) there is certain inhibiting effect, part of target compound to plant virus and
Phytopathogen is presented with excellent inhibitory activity, can be used as potential Antiphytoviral drug, has the prospect preferably applied.
In conclusion being only presently preferred embodiments of the present invention, it is not intended to limit the present invention in any form, appoints
What is to the above embodiments according to the technical essence of the invention any simply to repair without departing from technical solution of the present invention content
Change, 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 of amide containing oxadiazoles, general structure (A) is as follows:
,
Wherein: R is alkoxy, halogen atom and the nitro of the alkyl of 1-6 carbon atom, 1-6 carbon atom, the substituted benzene
Base is alkoxy, halogen and nitre o-, m-, to the alkyl containing one or 2 1-6 carbon atom, 1-6 carbon atom on phenyl ring
Base.
2. a kind of preparation method of the myricetin derivative of amide containing oxadiazoles, comprises the following steps that
(1) using semicarbazide hydrochloride, substituted benzaldehyde as raw material, using elemental iodine as oxidant, with methanol, water and Isosorbide-5-Nitrae-two
Six ring of oxygen is solvent, prepares 2- amino -5- substituted-phenyl -1,3,4- oxadiazoles:
；
(2) with 2- amino -5- substituted-phenyl -1,3,4- oxadiazoles and chloracetyl chloride are raw material, using potassium carbonate as catalyst, are used
N,N-Dimethylformamide and methylene chloride make solvent, and preparation 2- is chloro-N(5- phenyl substituent -1,3,4- oxadiazoles)-acetyl
Amine:
；
(3) using myricetrin and iodomethane as raw material, using potassium carbonate as catalyst, acidity, which is adjusted, prepares 3- hydroxyl -3 ', and 4 ', 5 ',
5,7- pentamethoxyl myricetin:
；
(4) with 3- hydroxyl -3 ', 4 ', 5 ', 5,7- pentamethoxyl myricetin and 2- are chloro-N(5- phenyl substituent -1,3,4- dislikes two
Azoles)-acetamide is raw material, it is catalyst with potassium carbonate, n,N-Dimethylformamide is that solvent prepares 2- ((5,7- dimethoxys-
4- ketone -2- (3,4,5- trimethoxyphenyl) -4HChromene -3- base) oxygroup -N(5- substituted-phenyl -1,3,4- oxadiazoles -2-
Base) acetamide:
。
3. a kind of myricetin derivative of amide containing oxadiazoles is used to prepare resisting tobacco mosaic virus disease, citrus processing and water
Application in terms of rice bacterial leaf spot pathogenic bacteria pesticide and disinfectant use in agriculture.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110183430A (en) * | 2019-06-18 | 2019-08-30 | 贵州大学 | 4-(N- methyl containing sulfonamide) amino piperidine myricetin derivative, Preparation method and use |
| CN111961039A (en) * | 2020-08-28 | 2020-11-20 | 贵州大学 | Myricetin derivative containing substituted pyrimidine, preparation method and application thereof |
| CN112194654A (en) * | 2020-08-28 | 2021-01-08 | 贵州大学 | Benzimidazolium-containing myricetin derivative, preparation method and application |
| CN112759581A (en) * | 2020-11-16 | 2021-05-07 | 贵州大学 | Benzoimidazole sulfonamide-containing myricetin derivative, preparation method and application |
| CN113582983A (en) * | 2021-07-13 | 2021-11-02 | 贵州大学 | Myricetin derivative of 1,3, 4-oxadiazole thioether, preparation method and application |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009076353A1 (en) * | 2007-12-10 | 2009-06-18 | The Biomedical Consulting & Development Co., Inc. | Compositions for protection against superficial vasodilator flush syndrome, and methods of use |
| WO2014162910A1 (en) * | 2013-04-03 | 2014-10-09 | 石原産業株式会社 | Preservative for cryopreservation of biological materials and method for preserving biological materials at low temperature |
| CN106518828A (en) * | 2016-11-02 | 2017-03-22 | 贵州大学 | Amides myricetin derivative and preparation method and application thereof |
| CN107021945A (en) * | 2017-05-02 | 2017-08-08 | 贵州大学 | A kind of analog derivative of myricetin containing piperazine acidamide and preparation method thereof |
| CN107602548A (en) * | 2017-09-14 | 2018-01-19 | 贵州大学 | A kind of myricetin derivative, the Preparation method and use of amide containing thioether thiadiazoles |
-
2018
- 2018-10-22 CN CN201811232349.2A patent/CN109438433B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009076353A1 (en) * | 2007-12-10 | 2009-06-18 | The Biomedical Consulting & Development Co., Inc. | Compositions for protection against superficial vasodilator flush syndrome, and methods of use |
| WO2014162910A1 (en) * | 2013-04-03 | 2014-10-09 | 石原産業株式会社 | Preservative for cryopreservation of biological materials and method for preserving biological materials at low temperature |
| CN106518828A (en) * | 2016-11-02 | 2017-03-22 | 贵州大学 | Amides myricetin derivative and preparation method and application thereof |
| CN107021945A (en) * | 2017-05-02 | 2017-08-08 | 贵州大学 | A kind of analog derivative of myricetin containing piperazine acidamide and preparation method thereof |
| CN107602548A (en) * | 2017-09-14 | 2018-01-19 | 贵州大学 | A kind of myricetin derivative, the Preparation method and use of amide containing thioether thiadiazoles |
Non-Patent Citations (1)
| Title |
|---|
| 肖维等: ""酰胺类杨梅素衍生物的合成及抑菌活性"", 《高等学校化学学报》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110183430A (en) * | 2019-06-18 | 2019-08-30 | 贵州大学 | 4-(N- methyl containing sulfonamide) amino piperidine myricetin derivative, Preparation method and use |
| CN110183430B (en) * | 2019-06-18 | 2020-06-05 | 贵州大学 | 4- (N-methyl) aminopiperidine myricetin derivative containing sulfamide, preparation method and application |
| WO2020253152A1 (en) * | 2019-06-18 | 2020-12-24 | 贵州大学 | Sulfonamide-containing 4-(n-methyl)aminopiperidine myricetin derivative, preparation method and application |
| CN111961039A (en) * | 2020-08-28 | 2020-11-20 | 贵州大学 | Myricetin derivative containing substituted pyrimidine, preparation method and application thereof |
| CN112194654A (en) * | 2020-08-28 | 2021-01-08 | 贵州大学 | Benzimidazolium-containing myricetin derivative, preparation method and application |
| CN112194654B (en) * | 2020-08-28 | 2022-11-08 | 贵州大学 | Benzimidazole-containing myricetin derivative, preparation method and application |
| CN112759581A (en) * | 2020-11-16 | 2021-05-07 | 贵州大学 | Benzoimidazole sulfonamide-containing myricetin derivative, preparation method and application |
| CN112759581B (en) * | 2020-11-16 | 2022-08-02 | 贵州大学 | Benzoimidazole sulfonamide-containing myricetin derivative, preparation method and application |
| CN113582983A (en) * | 2021-07-13 | 2021-11-02 | 贵州大学 | Myricetin derivative of 1,3, 4-oxadiazole thioether, preparation method and application |
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