CN103804386A - 4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative as well as synthetic method and application thereof - Google Patents
4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative as well as synthetic method and application thereof Download PDFInfo
- Publication number
- CN103804386A CN103804386A CN201410026948.4A CN201410026948A CN103804386A CN 103804386 A CN103804386 A CN 103804386A CN 201410026948 A CN201410026948 A CN 201410026948A CN 103804386 A CN103804386 A CN 103804386A
- Authority
- CN
- China
- Prior art keywords
- derivative
- indoles
- furans
- dihydroxyl
- spiral shell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 C*(C1)C1(C*)C#N Chemical compound C*(C1)C1(C*)C#N 0.000 description 4
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a 4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative as well as a synthetic method and an application thereof. The synthetic method comprises the following steps: in the presence of a solvent, carrying out a reaction on substituted or unsubstituted unsaturated nitrile ethyl acetate and an isatin derivative under catalysis of an alkali compound; and treating the reaction product to obtain the 4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative. The method has the advantages that reaction time is agile, yield is high, operation is simple and convenient and the like, and is wide in application range and suitable for industrialized production. The 4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative disclosed by the invention can be used as an antibacterial agent.
Description
Technical field
The present invention relates to the synthetic field of heterogeneous ring compound, be specifically related to a kind of 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative and synthetic method and application.
Background technology
Furan and its derivatives is the important heterogeneous ring compound of a class, is present in natural product widely, and has important biological activity.The physiological actions such as that a lot of furan derivatives have is antimycotic, desinsection; Very useful in the diseases such as the damage of increasing furan derivatives and ischemia central nervous system treatment (CNS) traumatic in treatment and arteriosclerosis, hepatopathy, the cerebrovascular.Therefore, synthetic furan derivatives has broad application prospects.
Meanwhile, indoles is also the very important heterogeneous ring compound of a class, and its homologue or derivative are present in occurring in nature widely, are with a wide range of applications at aspects such as medicine, agricultural chemicals, dyestuff and fine chemistry industries.Compound containing indole structure often has antibacterium and antimycotic effect, and a lot of natural alkaloids all have indoles spirane structure with the relevant compound of medicine.
On isatin, construct a furans heterocycle, form spiral shell [furans-2,3 '-indoles]-2 '-one derivative, and study their active bibliographical information few.
At present, the main literature of synthetic spiral shell [furans-2,3 '-indoles]-2 '-one derivative is as follows:
1.2002 years, Nair etc. reported under SnCl4 catalysis, and [3+2] cycloaddition reaction occurs for isatin and allyl silicane, has synthesized spiral shell [furans-2,3 '-indoles]-2 '-one derivative.（Nair,V;Rajesh,C;Dhanya,R;Rath,N.P.Tetrahedron?Lett.2002,43,5349.）
2.2005 years, Alcaide etc., take isatin and propargyl bromide as raw material, by series reaction, synthesized spiral shell [furans-2,3 '-indoles]-2 '-one derivative.（Alcaide,B;Almendros,P;Rodr1guez-Acebes,R.Chem.Eur.J.2005,11,5708.）
These methods have following deficiency, (1) substrate, and as allyl silicane, propargyl bromide, price comparison is expensive, is difficult for obtaining; (2) the reaction scope of application is wideless, and step is more complicated also; (3) do not study the activity of this compounds.
Therefore, need to develop a kind of new spiral shell [furans-2,3 '-indoles]-2 '-one derivative and new synthetic method thereof, and study their anti-mycotic activity.
Summary of the invention
The invention provides a kind of anti-fungal property good 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative.
A kind of 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, the compound for structure shown in formula I:
Wherein, R
1be selected from hydrogen, methyl, trifluoromethyl, chlorine or bromine.
It is above-mentioned 4 that the present invention also provides, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, and raw material is easy to get, easy and simple to handle, environmentally friendly.
The synthetic method of 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, comprises the following steps:
Under solvent exists, under basic compound catalysis, by Isatine derivatives, with replacement or do not replace undersaturated itrile group ethyl acetate and react, reaction product obtains 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative through aftertreatment;
Described replacement or not replace the structural formula of undersaturated itrile group ethyl acetate as follows:
Wherein, R
1be selected from hydrogen, methyl, trifluoromethyl, chlorine, bromine.
The structural formula of described Isatine derivatives is as follows:
Described solvent is selected the one in water, toluene, trichloromethane.These solvents have good solvability to raw material.
Described basic cpd is selected from the one in salt of wormwood, sodium carbonate, lithium hydroxide.The mechanism of action of these basic cpds is identical, and first, seize the proton on hydroxyl in Isatine derivatives, form negative oxygen ion, thereby the first step Mike addition reaction occurs.The second, in molecule, carry out again Mike's addition reaction.
Temperature of reaction is preferably 0 ℃～25 ℃, and the reaction times is preferably 5-15 hour.
Described aftertreatment can adopt the conventional post-treating method in synthetic field, and as adopted recrystallization or column chromatography to purify after extracting and separating, aftertreatment can comprise: add water, and ethyl acetate extraction, dry, use organic solvent recrystallization except after desolventizing.Organic solvent can be selected a kind of in ethyl acetate, sherwood oil or two kinds.
Or post-treating method can also be: be extracted with ethyl acetate, after being dried, removal of solvent under reduced pressure, then through column chromatography.The leacheate of column chromatography can be selected the mixed solution of sherwood oil and ethyl acetate.
It is described 4 that the present invention finally provides, and 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative is in the application as in anti-mycotic agent.Through evidence, 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has certain restraining effect to Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, five kinds of fungies of fusarium graminearum.
Take solvent existence condition as example, the reaction equation of the various stock yards of the present invention is as follows:
Reaction formula 1
Wherein, R
1be selected from hydrogen, methyl, trifluoromethyl, chlorine, bromine.
In the present invention, the consumption of reaction raw materials replacement or unsubstituted unsaturated nitrile guanidine-acetic acid ethyl ester and Isatine derivatives does not have strict restriction, generally measures than reacting according to chemical reaction, and can be also that wherein a kind of compound is excessive reacts.
In the present invention, the consumption of reaction solvent, catalyzer does not have strict restriction, can be according to the consumption adjustment of reaction raw materials: the consumption of the more increase reaction solvent of reaction raw materials and catalyzer, the consumption of the less minimizing reaction solvent of reaction raw materials and catalyzer.
Tool of the present invention has the following advantages:
The present invention 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles] synthetic method of-2 '-one derivative, its key problem in technology is to replace or unsubstituted unsaturated nitrile guanidine-acetic acid ethyl ester and Isatine derivatives are raw material, select cheap reaction solvent, select suitable basic cpd as catalyzer, one kettle way directly synthesizes 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative; Have flexible reaction time, yield is higher, and solvent is cheap and easy to get, easy and simple to handle, the applied widely many merits of Denging, is suitable for suitability for industrialized production.
Of the present invention 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative all has certain restraining effect to Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, five kinds of fungies of fusarium graminearum, and can be used as antiseptic-germicide and use.
Embodiment
Embodiment 1
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2a) (4.0g, 0.02mol), lithium hydroxide (0.092g, 0.004mol), 40mL toluene.Reaction mixture stirs 10 hours at 0 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3a as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a (7.7g, productive rate 83%).
Reaction equation is as follows:
By obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a identifies through nucleus magnetic resonance and high resolution mass spectrum,
1h NMR (400MHz, CDCl3) δ 7.82 (d, J=7.2Hz, 1H), 7.52 – 7.44 (m, 2H), 7.44 – 7.36 (m, 4H), 7.19 (t, J=7.3Hz, 1H), 6.84 (d, J=7.8Hz, 1H), 6.04 (s, 1H), 4.43 – 4.29 (m, 2H), 4.18 – 4.09 (m, 1H), 3.90 – 3.78 (m, 2H), 3.22 (s, 3H), 2.84 – 2.61 (m, 2H), 1.33 (t, J=7.1Hz, 3H), 1.03 (t, J=7.1Hz, 3H).
13c NMR (100MHz, CDCl3) δ 176.4,169.7,164.9,144.9,133.5,131.0,129.5,128.4; 127.1,126.6,124.3,123.2,115.5,108.6,84.9,83.5; 63.7,61.3,60.9,50.6,33.7,26.4,14.0,13.8; ESI-HRMS calcd for C26H26N2O6+Na485.1683, found485.1669. show to obtain 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3a.
Embodiment 2
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2a) (4.0g, 0.02mol), lithium hydroxide (0.092g, 0.004mol), 40mL water.Reaction mixture stirs 10 hours at 25 degree, then add ethyl acetate extraction, dry, removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3a as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a (6.5g, productive rate 70%).
Reaction equation is as follows:
By chloro-5-obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a identifies through nucleus magnetic resonance and high resolution mass spectrum, and result is with embodiment 1.Show to obtain 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3a.
Embodiment 3
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2a) (4.0g, 0.02mol), lithium hydroxide (0.092g, 0.004mol), 40mL toluene.Reaction mixture stirs 5 hours at 25 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3a as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a (7.4g, productive rate 80%).
Reaction equation is as follows:
By chloro-5-obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3a identifies through nucleus magnetic resonance and high resolution mass spectrum, and result is with embodiment 1.Show that the 5-obtaining is chloro-4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3a.
Embodiment 4
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2b) (4.3g, 0.02mol), lithium hydroxide (0.092g, 0.0040mol), 40mL toluene.Reaction mixture stirs 10 hours at 0 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3b as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3b (7.5g, productive rate 79%).Reaction equation is as follows:
By obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3b identifies through nucleus magnetic resonance and high resolution mass spectrum,
1h NMR (400MHz, CDCl
3) δ 7.82 (d, J=6.9Hz, 1H), 7.44 – 7.33 (m, 3H), 7.23 – 7.15 (m, 3H), 6.83 (d, J=7.8Hz, 1H), 6.00 (s, 1H), 4.35 (q, J=7.1Hz, 2H), 4.17 – 4.08 (m, 1H), 3.93 – 3.77 (m, 2H), 3.22 (s, 3H), 2.86 – 2.60 (m, 2H), 2.37 (s, 3H), 1.33 (t, J=7.1Hz, 3H), 1.03 (t, J=7.1Hz, 3H).
13c NMR (100MHz, CDCl
3) δ 176.4,169.7,165.0,144.9,139.3,130.9,130.4,129.1,127.1,126.5,124.3,123.2,115.6,108.5,85.0,83.5,63.6,61.3,60.9,50.5,33.7,26.3,21.3,14.0,13.8; ESI-HRMS calcd for C
27h
28n
2o
6+ Na499.1845, found499.1813. show to obtain 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3b.
Embodiment 5
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2c) (4.7g, 0.02mol), lithium hydroxide (0.092g, 0.0040mol), 40mL toluene.Reaction mixture stirs 10 hours at 0 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3c as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3c (8.7g, productive rate 87%).
Reaction equation is as follows:
By obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3c identifies through nucleus magnetic resonance and high resolution mass spectrum,
1h NMR (400MHz, CDCl
3) δ 7.79 (d, J=7.2Hz, 1H), 7.49 – 7.33 (m, 5H), 7.19 (t, J=7.5Hz, 1H), 6.84 (d, J=7.8Hz, 1H), 6.01 (s, 1H), 4.36 (q, J=7.1Hz, 2H), 4.16 – 4.05 (m, 1H), 3.92 – 3.80 (m, 2H), 3.22 (s, 3H), 2.87 – 2.58 (m, 2H), 1.34 (t, J=7.1Hz, 3H), 1.03 (t, J=7.1Hz, 3H).
13c NMR (100MHz, CDCl
3) δ 176.3,169.7,164.8,144.9,135.4,132.1,131.1,128.7,128.0,127.1,124.1,123.2,115.3,108.6,84.1,83.6,63.8,61.0,61.0,50.6,33.7,26.4,14.0,13.8; ESI-HRMS calcd for C
26h
25clN
2o
6+ Na519.1293, found519.1282; Show to obtain 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3c.
Embodiment 6
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2d) (5.5g, 0.02mol), lithium hydroxide (0.092g, 0.0040mol), 40mL toluene.Reaction mixture stirs 10 hours at 0 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3d as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3d (8.4g, productive rate 78%).
Reaction equation is as follows:
By chloro-5-obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3d identifies through nucleus magnetic resonance and high resolution mass spectrum,
1h NMR (400MHz, CDCl
3) δ 7.78 (d, J=7.4Hz, 1H), 7.53 (d, J=8.5Hz, 2H), 7.45 – 7.32 (m, 3H), 7.19 (t, J=7.6Hz, 1H), 6.84 (d, J=7.8Hz, 1H), 5.99 (s, 1H), 4.36 (q, J=7.1Hz, 2H), 4.16 – 4.05 (m, 1H), 3.91 – 3.73 (m, 2H), 3.22 (s, 3H), 2.86 – 2.58 (m, 2H), 1.34 (t, J=7.1Hz, 3H), 1.02 (t, J=7.1Hz, 3H).
13c NMR (100MHz, CDCl
3) δ 176.2,169.6,164.7,144.9,132.6,131.6,131.1,128.3,127.1,124.0,123.7,123.2,115.3,108.7,84.2,83.6,63.8,61.0,50.6,33.7,29.7,26.4,14.0,13.9; ESI-HRMS calcd for C
26h
25brN
2o
6+ Na563.0788, found563.0725. shows that the 5-obtaining is chloro-4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3d.
Embodiment 7
In 100mL reaction flask, put into Isatine derivatives (structural formula is as 1) (5.2g, 0.02mol), unsaturated nitrile guanidine-acetic acid ethyl ester (structural formula is as 2e) (5.4g, 0.02mol), lithium hydroxide (0.092g, 0.0040mol), 40mL toluene.Reaction mixture stirs 10 hours at 0 degree, then removal of solvent under reduced pressure, mixed solution take sherwood oil and ethyl acetate (sherwood oil and ethyl acetate volume ratio are as 10:1) obtains structural formula as 4 of 3e as leacheate carries out column chromatography, 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3e (7.5g, productive rate 71%).
Reaction equation is as follows:
By bromo-5-obtained above 4, the structure of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative 3e identifies through nucleus magnetic resonance and high resolution mass spectrum,
1h NMR (600MHz, CDCl
3) δ 7.79 (d, J=7.4Hz, 1H), 7.71 – 7.58 (m, 5H), 7.43 (t, J=7.7Hz, 1H), 7.21 (t, J=7.6Hz, 1H), 6.86 (d, J=7.8Hz, 1H), 6.10 (s, 1H), 4.38 (q, J=7.1Hz, 2H), 4.14 – 4.11 (m, 1H), 3.89 – 3.83 (m, 2H), 3.23 (s, 3H), 2.84 – 2.66 (m, 2H), 1.35 (t, J=7.1Hz, 3H), 1.03 (t, J=7.1Hz, 3H).
13c NMR (150MHz, CDCl
3) δ 176.2,169.6,164.7,144.9,137.6,131.7,131.1,127.1,125.4,125.4,124.7,123.9,123.3,122.9,115.2,108.7,83.9,83.7,63.9,61.0,61.0,50.7,33.6,26.4,14.0,13.8; ESI-HRMS calcd for C
27h
25f
3n
2o
6+ Na553.1557, found553.1518.Show that the 5-obtaining is bromo-4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has the structure shown in structural formula 3e.
Embodiment 8: the anti-microbial property evaluation of sample segment
1. anti-mycotic activity is measured process: the substratum preparation that contains different compounds: synthetic different compounds are dissolved in respectively to acetone, are made into the mother liquor of different concns.Draw respectively 1mL mother liquor and 9mL MEA substratum (20g Fructus Hordei Germinatus, 20g sucrose, 1g peptone, 1L water, 18g agar) in sterile test tube, after shake well, pour in sterile petri dish, make the final quality concentration of compound in substratum be respectively 100,50,10 and 1 μ g/mL, using equivalent acetone as blank.The phytopathogenic fungi of activation is broken into the bacterium piece that diameter is 5mm with aseptic punch tool, be placed in above-mentioned substratum, every processing repeats 3 times, under 28 ℃ of constant temperature, cultivates after 3～7 days, adopts right-angled intersection method to measure for examination bacterium colony diameter.Be calculated as follows inhibiting rate: inhibiting rate=(contrast colony diameter-processing colony diameter)/(contrast colony diameter-5mm) × 100%.
2. anti-microbial property
Known by table 1, all compound 3a-3e have and suppress active Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, five kinds of fungies of fusarium graminearum, particularly fine to Valsa mali, fusarium graminearum inhibiting rate.
The restraining effect of the lower different compounds of table 1. concentration of the same race (concentration is 50 μ g/mL) to 5 kind of plant pathomycetes
Then,, take Valsa mali, two kinds of bacterium of fusarium graminearum as main, all compounds are mixed with to different concns and do, and drawn IC
50(minimum inhibition concentration) value.Two IC in table 2
50value is less than 100, and wherein 3e and 3b performance are very good.
The concrete inhibition of table 2.2 kind of plant pathomycete
More than experiment showed, that 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative has certain restraining effect to Rhizoctonia solani Kuhn, bitter gourd wilt bacterium, tomato early blight bacterium, Valsa mali, five kinds of fungies of fusarium graminearum.
Claims (7)
1. one kind 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, the compound for structure shown in formula I:
Wherein, R
1be selected from hydrogen, methyl, trifluoromethyl, chlorine or bromine.
2. claimed in claim 14, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, comprises the following steps:
Under solvent exists, under basic compound catalysis, by Isatine derivatives, with replacement or do not replace undersaturated itrile group ethyl acetate and react, reaction product obtains 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative through aftertreatment;
The structural formula of described Isatine derivatives is as follows:
Described replacement or not replace the structural formula of undersaturated itrile group ethyl acetate as follows:
Wherein, R
1be selected from hydrogen, methyl, trifluoromethyl, chlorine, bromine.
3. according to claim 24, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, described solvent is the one in water, toluene, trichloromethane.
4. according to claim 24, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, described basic cpd is selected from the one in salt of wormwood, sodium carbonate, lithium hydroxide.
5. according to claim 24, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, temperature of reaction is 0 ℃～25 ℃, and the reaction times is 5-15 hour.
6. according to claim 34, the synthetic method of 5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative, is characterized in that, described aftertreatment comprises: removal of solvent under reduced pressure, then through column chromatography.
7. claimed in claim 14,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative is in the application as in antiseptic-germicide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410026948.4A CN103804386B (en) | 2014-01-21 | 2014-01-21 | 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative and synthetic method thereof and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410026948.4A CN103804386B (en) | 2014-01-21 | 2014-01-21 | 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative and synthetic method thereof and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103804386A true CN103804386A (en) | 2014-05-21 |
| CN103804386B CN103804386B (en) | 2016-01-06 |
Family
ID=50701817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410026948.4A Active CN103804386B (en) | 2014-01-21 | 2014-01-21 | 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative and synthetic method thereof and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103804386B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106565731A (en) * | 2016-11-01 | 2017-04-19 | 浙江师范大学 | Double-spiro isatin furan derivatives with antibacterial activity as well as synthesis method and application thereof |
| CN106699766A (en) * | 2016-12-28 | 2017-05-24 | 浙江师范大学 | Spiro-isatin thiourea derivative with antibacterial activity as well as synthesis method and application of derivative |
| CN108191879A (en) * | 2018-01-09 | 2018-06-22 | 滨州医学院 | One kind has antibacterial active compounds and its method for preparing purified and application |
| CN108285453A (en) * | 2018-01-09 | 2018-07-17 | 滨州医学院 | A kind of antimicrobial compound and its method for preparing purified and application |
| CN108395438A (en) * | 2018-04-03 | 2018-08-14 | 陕西科技大学 | One kind has the isatin parent nucleus spiro-compound and its synthetic method of antibacterial activity |
| CN115124544A (en) * | 2022-07-20 | 2022-09-30 | 四川抗菌素工业研究所金华分所 | Spiro [ tetrahydrofuran-3, 3' -indoline ] skeleton, crystal form thereof, preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022462A1 (en) * | 2006-08-25 | 2008-02-28 | University Of Northern British Columbia | Para-quinol derivatives and methods of stereo selectively synthesizing and using same |
| CN101845048A (en) * | 2010-06-13 | 2010-09-29 | 浙江师范大学 | Synthetic method of 2-nitro-2,3-dihydrofuran derivative |
| CN101851177A (en) * | 2010-06-13 | 2010-10-06 | 浙江师范大学 | Synthetic method of 5-nitryl-2,4-diphenyl cyclopentyl-2-ene-1,1-dinitrile and derivative thereof |
| CN102267964A (en) * | 2011-06-15 | 2011-12-07 | 浙江师范大学 | 3-hydroxy-2,3-dihydro-benzofuran derivatives as well as synthesis method and application thereof |
-
2014
- 2014-01-21 CN CN201410026948.4A patent/CN103804386B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008022462A1 (en) * | 2006-08-25 | 2008-02-28 | University Of Northern British Columbia | Para-quinol derivatives and methods of stereo selectively synthesizing and using same |
| CN101845048A (en) * | 2010-06-13 | 2010-09-29 | 浙江师范大学 | Synthetic method of 2-nitro-2,3-dihydrofuran derivative |
| CN101851177A (en) * | 2010-06-13 | 2010-10-06 | 浙江师范大学 | Synthetic method of 5-nitryl-2,4-diphenyl cyclopentyl-2-ene-1,1-dinitrile and derivative thereof |
| CN102267964A (en) * | 2011-06-15 | 2011-12-07 | 浙江师范大学 | 3-hydroxy-2,3-dihydro-benzofuran derivatives as well as synthesis method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| FAYE MAERTENS，等: "Incorporation of an indole-containing diarylbutylamine", 《TETRAHEDRON》 * |
| SENGODAGOUNDER MUTHUSAMY, THANGARAJU KARIKALAN: "Diastereoselective synthesis of macrocycles incorporating the spiro-indolofurans", 《TETRAHEDRON》 * |
| SENGODAGOUNDER MUTHUSAMY，等: "Multicomponent Reactions of Diazoamides: Diastereoselective", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106565731A (en) * | 2016-11-01 | 2017-04-19 | 浙江师范大学 | Double-spiro isatin furan derivatives with antibacterial activity as well as synthesis method and application thereof |
| CN106699766A (en) * | 2016-12-28 | 2017-05-24 | 浙江师范大学 | Spiro-isatin thiourea derivative with antibacterial activity as well as synthesis method and application of derivative |
| CN106699766B (en) * | 2016-12-28 | 2018-08-07 | 浙江师范大学 | It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application |
| CN108191879A (en) * | 2018-01-09 | 2018-06-22 | 滨州医学院 | One kind has antibacterial active compounds and its method for preparing purified and application |
| CN108285453A (en) * | 2018-01-09 | 2018-07-17 | 滨州医学院 | A kind of antimicrobial compound and its method for preparing purified and application |
| CN108191879B (en) * | 2018-01-09 | 2020-10-02 | 滨州医学院 | Application of compound with antibacterial activity |
| CN108285453B (en) * | 2018-01-09 | 2020-10-02 | 滨州医学院 | Application of antibacterial compound |
| CN108395438A (en) * | 2018-04-03 | 2018-08-14 | 陕西科技大学 | One kind has the isatin parent nucleus spiro-compound and its synthetic method of antibacterial activity |
| CN115124544A (en) * | 2022-07-20 | 2022-09-30 | 四川抗菌素工业研究所金华分所 | Spiro [ tetrahydrofuran-3, 3' -indoline ] skeleton, crystal form thereof, preparation method and application thereof |
| CN115124544B (en) * | 2022-07-20 | 2023-06-23 | 四川抗菌素工业研究所金华分所 | Spiro [ tetrahydrofuran-3, 3' -indoline ] framework and crystal form thereof, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103804386B (en) | 2016-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103804386B (en) | 4,5-dihydroxyl-3-H-spiral shell [furans-2,3 '-indoles]-2 '-one derivative and synthetic method thereof and application | |
| Reddy et al. | Indium (III) chloride catalyzed three-component coupling reaction: A novel synthesis of 2-substituted aryl (indolyl) kojic acid derivatives as potent antifungal and antibacterial agents | |
| CN103923034B (en) | A kind of pinane base-3-[4-(substituting group)-2-thiazole] hydrazone compounds and synthetic method thereof and application | |
| CN102267964B (en) | 3-hydroxy-2,3-dihydro-benzofuran derivatives as well as synthesis method and application thereof | |
| CN106699766B (en) | It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application | |
| RU2671202C1 (en) | Method for obtaining praziquantel and its intermediate compounds | |
| CN102816150B (en) | Indole with bacteriostatic activity and derivatives thereof-triazole compounds, and preparation method thereof | |
| Lin et al. | A convenient and efficient protocol for the synthesis of 1, 3, 5-triaryl-2-pyrazolines in acetic acid under ultrasound irradiation | |
| CN103910737A (en) | Chiral 1, 4-dihydropyran (2, 3-c) pyrazole derivative as well as synthesis method and application of chiral 1, 4-dihydropyran (2, 3-c) pyrazole derivative | |
| CN108503620B (en) | Formaldehyde fluorescent donor molecule and preparation method and application thereof | |
| Chakraborty et al. | Synthesis and antibacterial activities of some novel isoxazolidine derivatives derived from N-phenyl--chloro nitrone in water | |
| CN105777773B (en) | Thiophene [2,3 b] quinoline and its synthetic method and application | |
| CN104086525A (en) | Spiro[tetralone-tetrahydrothiophene] derivative having antibiosis activity, and synthetic method and application thereof | |
| CN103965183B (en) | Fluorine-containingoxazolidinonecompound as well as preparation method and application thereof | |
| CN106967086B (en) | It is a kind of with the quino sulphur pyran derivate and its synthetic method of antibacterial activity and application | |
| CN107162991A (en) | A kind of method that solvent participates in the reaction synthesis triazole compounds of 4 acetyl group 1,2,3 | |
| CN115160159B (en) | Halichonin B analogue, preparation method thereof and application thereof in preparing agricultural bactericide | |
| CN102516173A (en) | Synthesis method for laurocapram | |
| CN104910090B (en) | Dihydro-isoxazole class compound and its synthetic method | |
| CN105037318B (en) | 2- cyano -3- (bis- fluoro- 1,3- benzos dioxy -4- bases of 2,2-) acrylic compounds and preparation method thereof | |
| CN103204884B (en) | Containing phenothiazinyl and ferrocenyl double-core Mannich base and its preparation method and application | |
| CN106967088B (en) | A kind of preparation method of ticarcillin sodium | |
| CN113461632B (en) | Preparation method of methyl 3- ((4-fluorophenyl) sulfonyl) -4-hydroxy-2-methylthiazolidine-2-carboxylate | |
| Wang et al. | Catalytic Nucleophilic Addition of 3, 5-Dialkyl-4-nitroisoxazoles to Trifluoromethyl Ketones on Water | |
| Chakraborty et al. | One pot high yield synthesis of some novel isoxazolidine derivatives using N-methyl-α-chloro nitrone in water and their antibacterial activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191230 Address after: 314416 No.318, Nanjie Road, Yuanhua Town, Haining City, Jiaxing City, Zhejiang Province Patentee after: Haining Yuanhua Town Industrial Investment Co., Ltd Address before: 321004 No. 688 Yingbin Road, Zhejiang, Jinhua Patentee before: Zhejiang Normal University |
|
| TR01 | Transfer of patent right |