CN106699766B - It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application - Google Patents
It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a kind of spiral shell isatin β-thiosemicarbazone derivatives and its synthetic method and application, synthetic method to include：Using ethyl alcohol as solvent, catalyst need not be added, substitution isatin isothiocyanates is reacted with various diimines, and reaction product is post-treated to obtain spiral shell isatin β-thiosemicarbazone derivative.This method have flexible reaction time, yield is higher, it is easy to operate the advantages that, it is applied widely, be suitable for industrialized production.Spiral shell isatin β-thiosemicarbazone derivative of the present invention can prepare antiseptic.
Description
Technical field
The present invention relates to the synthesis fields 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.There is special in isatin spiro-heterocycle compound
The heterocycle of structure, and have in terms of inhibiting cell growth, anticancer, antianxiety, anti-inflammatory, analgesia and the medicine such as decompression and desinsection
Many important physiological activity.Therefore, isatin spiro-heterocycle compound is synthesized and studies to 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 was reported for the first time using schiff bases as catalyst, and tetrahydrofuran is solvent, and substitution isatin is different
Cascade reaction occurs for thiocyanates and phosphorimide, obtain spiral shell isatin β-thiosemicarbazone derivative (Angew.Chem.Int.Ed.2012,
51,7007–7010)。
(2) 2014 years, chemist then reported substitution isatin isothiocyanates under the catalysis of Takemoto catalyst, with
React to family's benzsulfamide, obtain spiral shell isatin β-thiosemicarbazone derivative (Chem.Commun., 2014,50,14771-
14774)。
(3) 2015 years, Yuan reports again replaced isatin isothiocyanates and tolysulfonyl imines using quinine as catalyst,
Reaction obtains spiral shell isatin β-thiosemicarbazone derivative (Tetrahedron 71 (2015) 949-955) in toluene.
In addition there are 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 have been synthesized, but have not studied the antibiotic property of such compound, in addition, what reaction used
Solvent is the bigger solvent of toxicity, causes serious pollution to the environment nor highly desirable.
Therefore, it is necessary 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 is studied its antibacterial activity.
Invention content
The present invention provides a kind of good spiral shell isatin β-thiosemicarbazone derivatives of antibacterial.
The present invention also provides a kind of raw materials to be easy to get, 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；
R2For C1~C3Alkyl.
Preferably, the spiral shell isatin β-thiosemicarbazone derivative is one kind in following compound：
The present invention also provides a kind of synthetic methods of the spiral shell isatin β-thiosemicarbazone derivative, including step：
Without under catalysts conditions, substitution isatin isothiocyanates is carried out instead with diimine derivative in alcohols solvent
It answers, obtains spiral shell isatin β-thiosemicarbazone derivative after processing.
The structural formula of the substitution isatin isothiocyanates is as follows：
The structural formula of the diimine derivative is as follows：
The mechanism of action of the present invention is as follows：The first, occur Mannich reaction, second, cyclization, proton transfer.
The alcohols solvent is ethyl alcohol.
The reaction temperature is 25~30 DEG C, and the reaction time is 1~5 hour.
The common post-processing approach in synthesis field can be used in the post-processing, is such as carried using recrystallization or column chromatography
Pure, post-processing may include：It is recrystallized with organic solvent after removing solvent.
The organic solvent can be selected one or two kinds of in ethyl acetate, petroleum ether.
Alternatively, the post-processing includes：Solvent is removed under reduced pressure, then through column chromatography.The leacheate of the column chromatography selects
With the mixed liquor of petroleum ether and ethyl acetate.
The spiral shell isatin β-thiosemicarbazone derivative can be used as antiseptic use, 4 kinds of common strain Escherichia coli (ATCC
8739), bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), salmonella (CMCC (B) 50115) into
Test is gone, such compound has certain antibacterial activity.
Preferably, when the spiral shell isatin β-thiosemicarbazone derivative is 3ae, the antiseptic is for inhibiting Salmonella
Bacterium；
When the spiral shell isatin β-thiosemicarbazone derivative is 3bj or 3bk, the antiseptic is for inhibiting bacillus subtilis
Bacterium.
By taking solvent existence condition as an example, the reaction equation between the various raw materials of the present invention is as follows：
Reaction equation (1)-(4)
R1Selected from hydrogen, methoxyl group, bromine, chlorine, trifluoromethyl.
There is no stringent limits for the dosage of reaction raw materials substitution isatin isothiocyanates and diimine derivative in the present invention
It is fixed, it is reacted generally according to chemical reaction metering ratio, can also be that one of which compound is excessively reacted.
There is no stringent restrictions for reaction dissolvent consumption in the present invention, can be adjusted according to the dosage of reaction raw materials：Reaction is former
Expect the more dosage for increasing reaction dissolvent, the less dosage 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, key problem in technology are substitution isatin isothiocyanates and double Asias
Amine derivative is raw material, does not need catalyst, and selects cheap reaction dissolvent, and one kettle way directly synthesizes spiral shell isatin β-thiosemicarbazone and spreads out
Biology；With flexible reaction time, yield is higher, and solvent is cheap and easy to get, easy to operate, and equal many merits applied widely are fitted
It is suitable for industrialized production.
Final object of the present invention is to provide application of the spiral shell isatin β-thiosemicarbazone derivative as antiseptic.
It is proved by a large amount of bacteriostatic experiment, spiral shell isatin β-thiosemicarbazone derivative of the invention can be used as antiseptic use, especially
It is to have certain inhibiting effect to salmonella, bacillus subtilis etc..
Specific implementation mode
Embodiment 1
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (208mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
Bright obtained spiral shell isatin β-thiosemicarbazone derivative has structure shown in structural formula 3aa.
Embodiment 2
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (276mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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,
The spiral shell isatin β-thiosemicarbazone derivative that found 509.0966. show has structure shown in structural formula 3ab.
Embodiment 3
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (363mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
The spiral shell isatin β-thiosemicarbazone derivative that 596.9959, found 596.9974. show has structure shown in structural formula 3ad.
Embodiment 4
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (344mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
Bright obtained spiral shell isatin β-thiosemicarbazone derivative has structure shown in structural formula 3ae.
Embodiment 5
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (232mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (268mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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 C28H28N4O3The spiral shell isatin sulphur that S+H501.1960, found 501.1963. show
Urea derivative has structure shown in structural formula 3af.
Embodiment 6
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (276mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
The spiral shell isatin β-thiosemicarbazone derivative that 481.0657, found 481.0651. show has structure shown in structural formula 3bi.
Embodiment 7
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (298mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
The spiral shell isatin β-thiosemicarbazone derivative that 503.1059, found 503.1119. show has structure shown in structural formula 3bj.
Embodiment 8
In 50 milliliters of reaction bulbs, be added 10 milliliters of ethyl alcohol, substitution isatin isothiocyanates 1a (204mg, 1mmol,
1.0eq) 1h is stirred at 25 DEG C with diimine derivative 2a (298mg, 1mmol, 1.0eq).Solvent then is removed under reduced pressure, with stone
(petroleum ether is 10 with ethyl acetate volume ratio for oily ether and ethyl acetate:1) mixed liquor is that leacheate progress column chromatography is tied
The 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
The spiral shell isatin β-thiosemicarbazone derivative arrived has structure shown in structural formula 3bk.
Embodiment 9：Bacteriostatic test
1. experimental strain：The present invention qualitatively judges the antibacterial activity of compound using inhibition zone method, using filter paper
4 kinds of common strain Escherichia colis (ATCC 8739) of piece method pair, bacillus subtilis (ATCC 6633), Candida albicans
(ATCC 10231), salmonella (CMCC (B) 50115) are 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 sterile 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：It is 50 μ g/ μ L that test-compound uses import DMSO dissolvings, configuration concentration respectively.
4. detection：It is (straight in sterile circular filter paper on piece that 2 μ L (2.5mg samples are dissolved in 50 μ L DMSO) are pipetted with liquid-transfering gun
Diameter：5mm), it is affixed on tablet, while making negative and positive control, then tablet is placed in 37 DEG C of constant incubators and is cultivated
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 salmonella, bacillus subtilis certain
Inhibiting effect, it is inactive to Escherichia coli, there was only weaker activity to Candida albicans.Compound is for 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
Outside, the also 3bj of nitro, 3bk then also have stronger activity to bacillus subtilis.
Claims (8)
1. a kind of spiral shell isatin β-thiosemicarbazone derivative, which is characterized in that shown in structure such as formula (I)：
R1Independently selected from H, halogen, CF3And methoxyl group；
R2For C1~C3Alkyl.
2. a kind of spiral shell isatin β-thiosemicarbazone derivative, which is characterized in that for one kind in following compound：
3. a kind of synthetic method of spiral shell isatin β-thiosemicarbazone derivative as claimed in claim 2, which is characterized in that including step：
Without under catalysts conditions, substitution isatin isothiocyanates is reacted with diimine derivative in alcohols solvent, is passed through
Spiral shell isatin β-thiosemicarbazone derivative is obtained after processing；
The structural formula of the substitution isatin isothiocyanates substrate is as follows：
The structural formula of the diimine derivative is as follows：
4. the synthetic method of spiral shell isatin β-thiosemicarbazone derivative according to claim 3, which is characterized in that the alcohols solvent
For ethyl alcohol.
5. the synthetic method of spiral shell isatin β-thiosemicarbazone derivative according to claim 3, which is characterized in that reaction temperature be 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, which is characterized in that the post-processing packet
It includes：Solvent is removed under reduced pressure, then the spiral shell isatin β-thiosemicarbazone derivative is obtained through column chromatography.
7. a kind of application of spiral shell isatin β-thiosemicarbazone derivative as claimed in claim 1 or 2 in preparing antiseptic, feature exist
In the antiseptic is for inhibiting salmonella or/and bacillus subtilis.
8. application of the spiral shell isatin β-thiosemicarbazone derivative in preparing antiseptic according to claim 7, which is characterized in that when described
Spiral shell isatin β-thiosemicarbazone derivative when being 3ae, the antiseptic is for inhibiting salmonella；
When the spiral shell isatin β-thiosemicarbazone derivative is 3bj or 3bk, the antiseptic is for inhibiting bacillus subtilis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201611236774.XA CN106699766B (en) | 2016-12-28 | 2016-12-28 | It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application |
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| CN108558895B (en) * | 2018-04-03 | 2021-04-06 | 陕西科技大学 | Isatin mother nucleus peroxide compound with antibacterial activity and preparation method 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 |
| CN112851559B (en) * | 2021-01-23 | 2022-11-08 | 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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