CN106699766A - Spiro-isatin thiourea derivative with antibacterial activity as well as synthesis method and application of derivative - Google Patents
Spiro-isatin thiourea derivative with antibacterial activity as well as synthesis method and application of derivative Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
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Abstract
The invention discloses a spiro-isatin thiourea derivative with antibacterial activity as well as a synthesis method and an application of the derivative. The synthesis method comprises steps as follows: ethanol is taken as a solvent, a catalyst is not required to be added, substituted isatin isothiocyanate and various diimine react, reaction products are treated, and the spiro-isatin thiourea derivative is obtained. The method has the advantages of being flexible in reaction time, higher in yield, simple and convenient to operate and the like and is wide in application range and suitable for industrial production. The spiro-isatin thiourea derivative can be used for preparing an antibacterial agent.
Description
Technical field
The present invention relates to the synthesis field of heterocyclic compound, and in particular to a kind of spiral shell isatin β-thiosemicarbazone derivative and its synthesis side
Method and application.
Background technology
Isatin, is the important skeleton for constructing nitrogen-containing hetero spiro-compound.It is special to be existed in isatin spiro-heterocycle compound
The heterocycle of structure, and suppress cell growth, anticancer, antianxiety, anti-inflammatory, analgesia and be depressured and the medicine such as desinsection in terms of have
Many important physiologically actives.Therefore, synthesize and study isatin spiro-heterocycle compound and have great importance.The structure of isatin
Formula is as follows：
There is the method for several synthesis spiral shell isatin β-thiosemicarbazone derivatives recently：
(1) 2012 year, chemist reported with schiff bases as catalyst first, and tetrahydrofuran is solvent, and substitution isatin is different
There is cascade reaction in thiocyanates and phosphorimide, obtain spiral shell isatin β-thiosemicarbazone derivative (Angew.Chem.Int.Ed.2012,
51,7007–7010)。
(2) 2014 years, chemist then report substitution isatin isothiocyanates under the catalysis of Takemoto catalyst, with
Family's benzsulfamide is reacted, spiral shell isatin β-thiosemicarbazone derivative (Chem.Commun., 2014,50,14771- is obtained
14774)。
(3) 2015 years, Yuan reported substitution isatin isothiocyanates and tolysulfonyl imines with quinine as catalyst again,
Reaction obtains spiral shell isatin β-thiosemicarbazone derivative (949-955 of Tetrahedron 71 (2015)) in toluene.
In addition with some other methods, but step is more cumbersome than three of the above, numerous to list herein.These methods
A series of spiral shell isatin β-thiosemicarbazone derivatives are synthesized, but have not studied the antibiotic property of such compound, additionally, reacting what is used
Solvent nor highly desirable, be toxicity than larger solvent, it is big for environment pollution.
Accordingly, it would be desirable to develop a kind of new spiral shell isatin β-thiosemicarbazone derivative and its new synthetic method, and study the anti-of them
Fungi activity.
The present invention obtains a kind of new spiral shell isatin β-thiosemicarbazone derivative by synthesis, and its antibacterial activity is studied.
The content of the invention
The invention provides a kind of good spiral shell isatin β-thiosemicarbazone derivative of antibacterial.
It is easy to get present invention also offers a kind of raw material, while easy to operate and environment amenable spiral shell isatin β-thiosemicarbazone derivative
Synthetic method.
A kind of spiral shell isatin β-thiosemicarbazone derivative, shown in structure such as formula (I)：
R1Independently selected from H, halogen, CF3And methoxyl group；
R2It is C1~C3Alkyl.
Preferably, described spiral shell isatin β-thiosemicarbazone derivative is the one kind in following compound：
Present invention also offers a kind of synthetic method of described spiral shell isatin β-thiosemicarbazone derivative, including step：
Under without catalysts conditions, substitution isatin isothiocyanates and diimine derivative are carried out instead in alcohols solvent
Should, spiral shell isatin β-thiosemicarbazone derivative is obtained after treatment.
The structural formula of described substitution isatin isothiocyanates is as follows：
The structural formula of described diimine derivative is as follows：
Mechanism of action of the invention is as follows：Firstth, there is Mannich reaction, second, cyclization, proton migration.
Described alcohols solvent is ethanol.
Described reaction temperature is 25~30 DEG C, and the reaction time is 1~5 hour.
The post-processing approach that described post processing can be commonly used using synthesis field, is such as carried using recrystallization or column chromatography
Pure, post processing may include：Recrystallized with organic solvent after removing solvent.
Described organic solvent can select the one or two kinds of in ethyl acetate, petroleum ether.
Or, described post processing includes：Removal of solvent under reduced pressure, then through column chromatography.The leacheate choosing of described column chromatography
With petroleum ether and the mixed liquor of ethyl acetate.
Described spiral shell isatin β-thiosemicarbazone derivative can be used as antiseptic, 4 kinds of common strain Escherichia coli (ATCC
8739), bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), salmonella (CMCC (B) 50115) enters
Test is gone, such compound has certain antibacterial activity.
Preferably, when described spiral shell isatin β-thiosemicarbazone derivative is 3ae, described antiseptic is used to suppress Salmonella
Bacterium；
When described spiral shell isatin β-thiosemicarbazone derivative is 3bj or 3bk, described antiseptic is used to suppress bacillus subtilis
Bacterium.
By taking solvent existence condition as an example, the reaction equation between various raw materials of the invention is as follows：
Reaction equation (1)-(4)
R1Selected from hydrogen, methoxyl group, bromine, chlorine, trifluoromethyl.
Reaction raw materials substitution isatin isothiocyanates does not have strict limit with the consumption of diimine derivative in the present invention
It is fixed, reacted generally according to chemical reaction metering ratio, or one of which compound is excessively reacted.
Reaction dissolvent consumption does not have strict restriction in the present invention, can be adjusted according to the consumption of reaction raw materials：Reaction is former
The more consumption for increasing reaction dissolvent of material, the less consumption for reducing reaction dissolvent of reaction raw materials.
The invention has the advantages that：
The synthetic method of spiral shell isatin β-thiosemicarbazone derivative of the present invention, its key problem in technology is substitution isatin isothiocyanates and double Asias
Amine derivative is raw material, it is not necessary to catalyst, and selects cheap reaction dissolvent, one kettle way to be directly synthesized spiral shell isatin β-thiosemicarbazone and spread out
It is biological；With flexible reaction time, yield is higher, and solvent is cheap and easy to get, easy to operate, applied widely to wait many merits, fits
It is suitable for industrialized production.
Final object of the present invention is the application for providing spiral shell isatin β-thiosemicarbazone derivative as antiseptic.
Proved by substantial amounts of bacteriostatic experiment, spiral shell isatin β-thiosemicarbazone derivative of the invention can be used as antiseptic, especially
It is have certain inhibitory action to salmonella, bacillus subtilis etc..
Specific embodiment
Embodiment 1
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (208mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3aa (400mg, yield 91%) of structure formula such as 3aa.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3aa obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR(600MHz,CDCl3) δ 7.97 (s, 1H), 7.72 (d, J=7.3Hz, 1H), 7.60-7.54 (m, 3H), 7.40 (t,
J=7.7Hz, 1H), 7.34-7.26 (m, 3H), 7.22-7.17 (m, 3H), 6.97 (d, J=7.3Hz, 2H), 6.75 (d, J=
7.9Hz,1H),5.57(s,1H),3.51–3.44(m,1H),3.04–2.98(m,1H),1.17–1.09(m,1H),1.01–
0.93 (m, 1H), 0.54 (t, J=7.4Hz, 3H)13C NMR(150MHz,CDCl3)δ183.5,172.1,151.1,143.6,
133.7,131.3,131.0,130.4,129.0,128.5,127.8,127.1,126.6,124.8,123.4,108.8,74.1,
68.6,41.7,20.3,11.1.ESI-HRMS:calcd for C26H24N4OS+H 441.1749, found 441.1740. tables
The bright spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3aa.
Embodiment 2
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (276mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3ab (472mg, yield 93%) of structure formula such as 3ab.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3ab obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 9.83 (s, 1H), 7.81 (s, 1H), 7.70 (d, J=7.3Hz, 1H), 7.58 (d, J=
8.5Hz, 2H), 7.47-7.41 (m, 3H), 7.32 (d, J=8.5Hz, 2H), 7.21 (t, J=7.5Hz, 1H), 7.03 (d, J=
7.9Hz, 1H), 6.89 (d, J=8.4Hz, 2H), 5.90 (s, 1H), 3.22-3.16 (m, 1H), 1.17-1.11 (m, 2H),
1.09-1.02 (m, 1H), 0.51 (t, J=7.4Hz, 3H)13C NMR(150MHz,DMSO)δ182.9,172.2,147.5,
143.7,135.1,133.8,133.2,131.2,131.0,129.5,129.1,128.8,127.2,125.2,123.5,
109.5,71.2,68.4,41.3,20.5,11.1.ESI-HRMS:calcd for C26H22Cl2N4OS+H 509.0970,
Found 509.0966. show that the spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3ab.
Embodiment 3
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (363mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3ad (524mg, yield 88%) of structure formula such as 3ad.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3ad obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 9.84 (s, 1H), 7.80 (s, 1H), 7.71 (d, J=7.4Hz, 1H), 7.60 (d, J=
8.5,1.8Hz, 2H), 7.52 (d, J=8.5Hz, 2H), 7.48-7.41 (m, 3H), 7.22 (t, J=7.5Hz, 1H), 7.05 (d,
J=7.9Hz, 1H), 6.83 (d, J=8.4Hz, 2H), 5.89 (s, 1H), 3.25-3.18 (m, 1H), 1.20-1.11 (m, 2H),
1.10-1.02 (m, 1H), 0.53 (t, J=7.4Hz, 3H)13C NMR(150MHz,DMSO)δ182.9,172.2,170.8,
147.4,143.7,133.5,132.3,131.7,131.3,131.2,129.5,129.4,127.2,125.2,123.9,
123.5,122.5,109.5,71.2,68.4,41.3,20.5,11.2.ESI-HRMS:calcd for C26H22Br2N4OS+H
596.9959, found 596.9974. show that the spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3ad.
Embodiment 4
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (344mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3ae (374mg, yield 65%) of structure formula such as 3ae.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3ae obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR(600MHz,CDCl3) δ 7.97 (s, 1H), 7.72 (d, J=7.3Hz, 1H), 7.60-7.54 (m, 3H), 7.40 (t,
J=7.7Hz, 1H), 7.34-7.26 (m, 3H), 7.22-7.17 (m, 3H), 6.97 (d, J=7.3Hz, 2H), 6.75 (d, J=
7.9Hz,1H),5.57(s,1H),3.51–3.44(m,1H),3.04–2.98(m,1H),1.17–1.09(m,1H),1.01–
0.93 (m, 1H), 0.54 (t, J=7.4Hz, 3H)13C NMR(150MHz,CDCl3)δ183.5,172.1,151.1,143.6,
133.7,131.3,131.0,130.4,129.0,128.5,127.8,127.1,126.6,124.8,123.4,108.8,74.1,
68.6,41.7,20.3,11.1.ESI-HRMS:calcd for C26H24N4OS+H 441.1749, found 441.1740. tables
The bright spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3ae.
Embodiment 5
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (268mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3af (350mg, yield 70%) of structure formula such as 3af.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3af obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 9.76 (s, 1H), 7.87 (s, 1H), 7.72 (d, J=7.3Hz, 1H), 7.43 (td, J=
7.8,0.9Hz, 1H), 7.31 (t, J=7.9Hz, 1H), 7.22 (t, J=7.5Hz, 1H), 7.16-7.11 (m, 3H), 7.03 (d,
J=7.9Hz, 1H), 6.98 (d, J=8.2,2.2Hz, 1H), 6.82 (d, J=8.2,2.3Hz, 1H), 6.47 (d, J=7.7Hz,
1H),6.39(s,1H),5.81(s,1H),3.75(s,3H),3.57(s,3H),3.23–3.14(m,1H),1.14–1.08(m,
1H), 1.06-1.00 (m, 1H), 0.53 (t, J=7.4Hz, 3H)13C NMR(150MHz,DMSO)δ183.2,172.3,
159.9,159.4,149.5,143.9,135.7,133.56,131.1,130.3,129.8,127.3,125.2,123.4,
120.5,119.6,116.6,114.2,113.0,112.0,109.3,72.1,68.6,55.6,55.3,41.2,20.5,
11.2.ESI-HRMS:calcd for C28H28N4O3S+H501.1960, found 501.1963. show the spiral shell isatin sulphur for obtaining
Urea derivative has the structure shown in structural formula 3af.
Embodiment 6
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (276mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3bi (408mg, yield 91%) of structure formula such as 3bi.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3bi obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 9.96 (s, 1H), 7.97 (d, J=6.9Hz, 1H), 7.64 (d, J=7.4Hz, 1H),
7.58 (s, 1H), 7.46-7.37 (m, 5H), 7.35-7.30 (m, 2H), 7.17 (t, J=11.0,4.1Hz, 1H), 7.06 (m, J
=14.4,6.9,5.2Hz, 2H), 6.19 (s, 1H), 2.91 (s, 3H)13C NMR(150MHz,DMSO)δ181.6,171.4,
133.5,132.3,131.9,131.5,131.1,130.9,130.3,130.1,130.0,129.0,128.1,127.6,
127.2,124.7,123.8,109.4,100.0,67.7,26.7.ESI-HRMS:calcd for C24H18Cl2N4OS+H
481.0657, found 481.0651. show that the spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3bi.
Embodiment 7
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (298mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3bi (401mg, yield 80%) of structure formula such as 3bj.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3bj obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 10.01 (s, 1H), 8.40 (s, 1H), 8.22-8.19 (m, 1H), 8.17 (d, J=8.3,
1.6Hz, 1H), 8.01 (d, J=7.9Hz, 1H), 7.92 (s, 1H), 7.71 (t, J=6.5Hz, 2H), 7.61 (t, J=8.0Hz,
1H), 7.49 (t, J=11.3,4.3Hz, 1H), 7.36 (d, J=7.8Hz, 1H), 7.26 (t, J=7.5Hz, 1H), 7.06 (d, J
=7.9Hz, 1H), 6.12 (s, 1H), 2.79 (s, 3H)13C NMR(150MHz,DMSO)δ182.7,171.9,148.6,
147.9,145.2,143.7,136.2,134.3,134.0,133.5,131.5,130.9,130.6,127.6,124.9,
124.3,124.1,122.0,121.8,109.7,70.2,68.4,26.6.ESI-HRMS:calcd for C24H18N6O5S+H
503.1059, found 503.1119. show that the spiral shell isatin β-thiosemicarbazone derivative for obtaining has the structure shown in structural formula 3bj.
Embodiment 8
In 50 milliliters of reaction bulbs, add 10 milliliters of ethanol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred with diimine derivative 2a (298mg, 1mmol, 1.0eq) at 25 DEG C.Subsequent removal of solvent under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is tied for leacheate carries out column chromatography
Spiral shell isatin β-thiosemicarbazone derivative 3bk (386mg, yield 77%) of structure formula such as 3bk.Reaction equation is as follows：
The structure of spiral shell isatin β-thiosemicarbazone derivative 3bk obtained above is reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed,1H NMR (600MHz, DMSO) δ 10.03 (s, 1H), 8.41 (s, 1H), 8.20 (dd, J=23.6,8.3Hz, 2H), 8.03
(d, J=7.9Hz, 1H), 7.93 (s, 1H), 7.74-7.67 (m, 3H), 7.62 (t, J=8.0Hz, 1H), 7.51 (t, J=
7.7Hz, 1H), 7.37 (d, J=7.7Hz, 1H), 7.27 (t, J=7.5Hz, 1H), 7.07 (d, J=7.9Hz, 1H), 6.13 (s,
1H),2.81(s,3H).13C NMR(150MHz,DMSO)δ182.7,171.9,148.6,147.9,145.3,143.7,136.2,
134.3,134.0,133.5,131.5,130.9,130.6,127.6,124.9,124.3,124.1,122.0,121.8,
109.7,68.4,26.6.ESI-HRMS:calcd for C24H18N6O5S+H 503.1059, found 503.1125. show
To spiral shell isatin β-thiosemicarbazone derivative there is structure shown in structural formula 3bk.
Embodiment 9：Bacteriostatic test
1. experimental strain：The present invention uses the antibacterial activity that inhibition zone method qualitatively judges compound, using filter paper
The piece method strain Escherichia coli (ATCC 8739) common to 4 kinds, bacillus subtilis (ATCC 6633), Candida albicans
(ATCC 10231), salmonella (CMCC (B) 50115) is tested.
2. prepared by bacterium solution：Strain liquid broth (peptone 10g, beef extract 3g, sodium chloride 5g, distilled water 1L,
PH 7.2~7.4) 37 DEG C, 180r/min shaking table culture 12h, then aseptic liquid-transfering gun pipette 200 μ L bacteria suspensions (bacterial concentration be
1.0×105CFU/ml) in corresponding culture medium, coating is uniform.
3. prepared by liquid：Test-compound is dissolved with import DMSO respectively, and configuration concentration is 50 μ g/ μ L.
4. detect：2 μ L (2.5mg samples are dissolved in 50 μ L DMSO) are pipetted in (straight in aseptic circular filter paper piece with liquid-transfering gun
Footpath：5mm), flat board is affixed on, while making negative and positive control, then flat board culture in 37 DEG C of constant incubators is placed in
15h, with the size of vernier caliper measurement antibacterial circle diameter, with feminine gender, positive group control, each sample parallel testing three times takes
Average value.
5. result：The results show spiral shell isatin β-thiosemicarbazone derivative has certain to salmonella, bacillus subtilis
Inhibitory action, it is inactive to Escherichia coli, there was only weaker activity to Candida albicans.Compound is directed to salmonella, withered grass
The anti-microbial property of bacillus is as shown in table 2-1：
Table 2-1 antifungal activities
By in the visible all test compounds of table, the 3ae containing trifluoromethyl has stronger activity to salmonella, separately
Outward, the also 3bj of nitro, 3bk then also have stronger activity to bacillus subtilis.
Claims (9)
1. a kind of spiral shell isatin β-thiosemicarbazone derivative, it is characterised in that shown in structure such as formula (I)：
R1Independently selected from H, halogen, CF3And methoxyl group；
R2It is C1~C3Alkyl.
2. spiral shell isatin β-thiosemicarbazone derivative according to claim 1, it is characterised in that be the one kind in following compound：
3. a kind of synthetic method of spiral shell isatin β-thiosemicarbazone derivative as claimed in claim 1 or 2, it is characterised in that including step：
Under without catalysts conditions, substitution isatin isothiocyanates is reacted with diimine derivative in alcohols solvent, passed through
Spiral shell isatin β-thiosemicarbazone derivative is obtained after treatment；
The structural formula of described substitution isatin isothiocyanates substrate is as follows：
The structural formula of described diimine derivative is as follows：
4. the synthetic method of spiral shell isatin β-thiosemicarbazone derivative according to claim 3, it is characterised in that described alcohols solvent
It is ethanol.
5. the synthetic method of spiral shell isatin β-thiosemicarbazone derivative according to claim 3, it is characterised in that reaction temperature is 20~
30 DEG C, the reaction time is 1~5 hour.
6. the synthetic method of spiral shell isatin β-thiosemicarbazone derivative according to claim 4, it is characterised in that described post processing bag
Include：Removal of solvent under reduced pressure, then obtain described spiral shell isatin β-thiosemicarbazone derivative through column chromatography.
7. application of a kind of spiral shell isatin β-thiosemicarbazone derivative as claimed in claim 1 or 2 in antiseptic is prepared.
8. application of the spiral shell isatin β-thiosemicarbazone derivative in antiseptic is prepared according to claim 7, it is characterised in that described
Antiseptic is used to suppress salmonella or/and bacillus subtilis.
9. application of the spiral shell isatin β-thiosemicarbazone derivative in antiseptic is prepared according to claim 7, it is characterised in that when described
Spiral shell isatin β-thiosemicarbazone derivative when being 3ae, described antiseptic is used to suppress salmonella；
When described spiral shell isatin β-thiosemicarbazone derivative is 3bj or 3bk, described antiseptic is used to suppress bacillus subtilis.
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| 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 |
| CN108558895A (en) * | 2018-04-03 | 2018-09-21 | 陕西科技大学 | One kind has the isatin parent nucleus per-compound and preparation method thereof of bacteriostatic activity |
| CN110963996A (en) * | 2017-10-25 | 2020-04-07 | 西南大学 | Indanazolol compound containing acetophenone substituent, preparation method and medical application thereof |
| CN112851559A (en) * | 2021-01-23 | 2021-05-28 | 中国人民解放军空军军医大学 | FtsZ and QseC double-target antibacterial molecule and preparation method and application thereof |
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| CN103804386A (en) * | 2014-01-21 | 2014-05-21 | 浙江师范大学 | 4, 5-dyhydroxyl-3-H-spiro[furan-2, 3'-indole]-2'-ketone derivative as well as synthetic method and application thereof |
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| WO2011006936A1 (en) * | 2009-07-15 | 2011-01-20 | Merck Serono S.A. | Tricyclic indole-derived spiro derivatives as crth2 modulators |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110963996A (en) * | 2017-10-25 | 2020-04-07 | 西南大学 | Indanazolol compound containing acetophenone substituent, preparation method and medical application thereof |
| CN110963996B (en) * | 2017-10-25 | 2022-09-09 | 西南大学 | Indanazolol compound containing acetophenone substituent, preparation method and medical application thereof |
| 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 |
| CN108558895A (en) * | 2018-04-03 | 2018-09-21 | 陕西科技大学 | One kind has the isatin parent nucleus per-compound and preparation method thereof of bacteriostatic activity |
| CN112851559A (en) * | 2021-01-23 | 2021-05-28 | 中国人民解放军空军军医大学 | FtsZ and QseC double-target antibacterial molecule and preparation method and application thereof |
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