CN110452204A - Xanthatin thioether class and imines analog derivative and its preparation method and application - Google Patents

Xanthatin thioether class and imines analog derivative and its preparation method and application Download PDF

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CN110452204A
CN110452204A CN201910756336.3A CN201910756336A CN110452204A CN 110452204 A CN110452204 A CN 110452204A CN 201910756336 A CN201910756336 A CN 201910756336A CN 110452204 A CN110452204 A CN 110452204A
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xanthatin
thiophenol
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analog derivative
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CN110452204B (en
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郅晓燕
蒋凌芸
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Shanxi Agricultural University
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/12—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings condensed with a carbocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • 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
    • A01N43/74—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 five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
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  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to Xanthatin thioether classes and imines analog derivative and its preparation method and application, being using Xanthatin as raw material, triethylamine is base, methanol is solvent and different mercaptan/thiophenol generation Michael addition reaction, obtain Xanthatin thioether class and imines analog derivative, general structure are as follows:Such compound has preferable inhibition plant pathogenic fungi spore germination activity and the insecticidal activity to diamondback moth larvae, can be used for preparing efficient, less toxic plant-source antibacterial agent/insecticide.

Description

Xanthatin thioether class and imines analog derivative and its preparation method and application
Technical field
The present invention relates to Xanthatin analog derivative technical field more particularly to Xanthatin thioether class and imines analog derivative and Preparation method and application.
Background technique
Xanthatin (Xanthatin) is one of composite family (Asteraceae) Xanthium (Xanthum L.) plant sesquialter Terpene lactones substance, because it is due to antitumor, anti-oxidant, anti-inflammatory, anti-malarial, antibacterial, desinsection etc. are permitted various bioactivity Focus as research.Wherein, document [Takeda S, Matsuo K, Yaji K, et al. (-)-Xanthatin selectively induces GADD45and stimulates caspase independent cell death in human breast cancer MDA-MB-231cells.Chemical Research in Toxicology,2011,24 (6):855-865.]、[Zhang L,Ruan J.S,Yan L.G,et al.Xanthatin induces cell cycle arrest at G2/M checkpoint and apoptosis via disrupting NF-κB pathway in A549non-small-cell lung cancer cells.Molecules, 2012a, 17 (4): 3736-3750.] and [Zhang L,Tao L,Ruan J.S,et al.Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45cells.Planta Medica,2012b,78(9): 890-895.] it reports Xanthatin and can inhibit the proliferation of kinds of tumor cells and apoptosis-induced, including human breast carcinoma MDA-MB- 231 cells, lung cancer A549 non-small cell and human gastric cancer MNK-45 cell.Document [Pinel B, Landreau A, Seraphin D,et al.Synthesis of reduced xanthatin derivatives and in vitro evaluation of their antifungal activity.Journal of Enzyme Inhibition and Medicinal Chemistry, 2005,20 (6): 575-579.] Xanthatin is reported to Candida glabrata, Candida albicans, aspergillus fumigatus Extracorporeal antifungal activity.Document [Saha D, Kumar R, Ghosh S, et al.Control of foliar diseases of tea with Xanthium strumarium leaf extract.Industrial Crops and Products, 2012,37 (1): 376-382.] Xanthatin is had studied to tealeaves leaf spot fungi, leaf spoting bacteria, brown patch germ and Cercospora Sojina Hara Antifungal activity, inhibitory effect is most preferably to leaf spot fungi, followed by brown patch germ.[Meng Xueying, Shen Huimin are grey for document The structural modification and its insecticidal activity assay of ear extract Xanthatin, agriculture of gansu journal, 2015, (3): 102-112.] report By the partial derivatives that Xanthatin chemical structure is transformed not only there is the female adult mite of Tetranychus urticae in road tags well Activity, and to oriental armyworm there are also it is good tag, stomach toxicity and Antifeedant Effects.
But literature survey find, at present Xanthatin thio-ether type compounds inhibit plant pathogenic fungi spore germination and Activity in terms of the stomach toxicity of diamondback moth is had not been reported.
Summary of the invention
The object of the present invention is to provide the new Xanthatin analog derivatives of series, and give the preparation method of derivative. It is proved according to test, Xanthatin thioether class and imines analog derivative have antibacterial activity and insecticidal activity efficiently, less toxic, can It is used to prepare plant-source antibacterial agent/insecticide.
To realize above-mentioned task, the present invention is achieved by following technical measures:
Xanthatin thioether class and imines analog derivative, chemical general formula are as follows:
R in chemical general formula is respectively below any:
It is grey to be that solvent makes using triethylamine as base, methanol for the preparation method of the Xanthatin thioether class and imines analog derivative From different mercaptan/thiophenol Michael addition reaction occurs for ear pavilion, obtains serial Xanthatin thioether class and imines analog derivative.
Specifically follow these steps to prepare:
It takes a certain amount of Xanthatin to be dissolved in methanol, 1-2 drop triethylamine is added after 10min is stirred at 0-5 DEG C, then slowly Corresponding mercaptan/thiophenol methanol solution is added, TLC tracing detection is concentrated under reduced pressure after reaction, prepares silica gel thin-layer chromatography Spectrum separates to obtain required target product.
Wherein, mercaptan/thiophenol used is respectively as follows:
Cyclohexylmercaptan, benzyl mercaptan, 3- methylbenzene phenyl-sulfhydrate, toluene-ω-thiol, 2,4- thiophenol dimethyl benzene, 4- ethylo benzene sulphur Phenol, 4- tert .- butylthiophenol, 2- methoxybenzenethiol, 2- fluoro thiophenol, 3- fluoro thiophenol, 4- fluoro thiophenol, 2,4 difluorobenzene Thiophenol, 3- chlorothio-phenol, 4- chlorothio-phenol, 2,4 dichloro benzene thiophenol, 2- bromo thiophenol, 3- bromo thiophenol, 4- bromo thiophenol, 2- Thionaphthol, 2- methyltetrahydrofuran -3- mercaptan, 2- methyl -3- furanthiol, 2- mercaptopyridine, 4- mercaptopyridine, 2- sulfydryl benzene And thiazole.
The Xanthatin thioether class and imines analog derivative can be used for preparing plant-source antibacterial agent/insecticide.
Xanthatin thioether class of the present invention and imines analog derivative have preferable inhibition plant pathogenic fungi spore Germination activity and insecticidal activity to diamondback moth larvae.Wherein, the antibacterial insecticidal activity of part of compounds is higher than parent Xanthatin, The spore germination inhibitor difenoconazole and hymexazol that the spore germination inhibitory activity of some compounds has higher than been commercialized, And the plant insecticide toosendanin that the insecticidal activity of certain compounds has higher than listed, therefore its be expected to be used for preparation efficiently, Plant-source antibacterial agent/insecticide of low toxicity.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy of compound 2；
Fig. 2 is the carbon-13 nmr spectra of compound 2；
Fig. 3 is the nuclear magnetic resonance spectroscopy of compound 14；
Fig. 4 is the carbon-13 nmr spectra of compound 14；
Fig. 5 is the nuclear magnetic resonance spectroscopy of compound 22；
Fig. 6 is the carbon-13 nmr spectra of compound 22.
Specific embodiment
The embodiment provided below by way of attached drawing and inventor is elaborated further the present invention.
The present invention has synthesized serial Xanthatin thioether class and imines analog derivative, and to its antibacterial activity and insecticidal activity into Row research.The result shows that Xanthatin thioether class and imines analog derivative the spore of test plant pathogen is shown it is stronger Inhibiting germination effect, shows stronger stomach poison activity to the diamondback moth in two latter stages in age, therefore it is efficient, low toxicity to be expected to be used for preparation Plant-source antibacterial agent/insecticide.
The following are the synthetic routes of compound 1-23:
It takes a certain amount of Xanthatin to be dissolved in methanol, triethylamine is added after stirring 10min at 0-5 DEG C, is slow added into phase Corresponding mercaptan/thiophenol methanol solution, TLC tracing detection prepare silica gel thin-layer chromatography point to after reaction, be concentrated under reduced pressure From obtaining required target product.
Reaction formula is as follows:
The serial number of compound 1-23 and substituent R corresponds.The physicochemical property of compound 1 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.07 (d, J=16.0Hz, 1H, 2-H), 6.23-6.25 (m, 1H, 5-H), 6.20 (d, J=16.0Hz, 1H, 3-H), 4.29-4.34 (m,1H,8-H),3.04-3.06(m,2H),2.88-2.93(m,1H,10-H),2.78-2.82(m,1H),2.68-2.70(m, 1H),2.60-2.62(m,1H),2.33-2.35(m,1H,6-H),2.30(s,3H,15-H),2.16-2.21(m,1H,6-H), 1.98-2.04 (m, 3H), 1.75-1.77 (m, 3H), 1.61-1.62 (m, 1H), 1.31-1.32 (m, 5H), 1.17 (d, J= 6.5Hz,3H,14-H)；13C NMR(125MHz,CDCl3)δ:198.55,176.16,148.47,144.63,138.96, 124.59,81.29,48.49,47.24,45.02,36.17,33.63,33.43,28.97,28.80,28.64,27.79, 26.00,25.74,18.51.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24ClO3S([M+H]+)363.1994,found 363.1992.
The physicochemical property of compound 2 is as follows:
1) white solid, 117.4-118.1 DEG C of fusing point；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.25- 7.32 (m, 5H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.16-6.19 (m, 2H, 3-H and 5-H), 4.25- 4.29(m,1H,8-H),3.77(s,2H,-CH 2), Ph 3.02-3.03 (m, 1H, 9-H), 2.89 (d, J=13.5Hz, 1H, 13- ), H 2.79 (dd, J=13.0,5.5Hz, 1H, 13-H), 2.67-2.72 (m, 1H, 10-H), 2.52-2.54 (m, 1H, 7-H), 2.29-2.33(m,4H,15-Hand 6-H),2.06-2.12(m,1H,6-H),1.92-1.99(m,1H,11-H),1.70- 1.75 (m, 1H, 9-H), 1.15 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.47,176.00, 148.38,144.59,138.80,137.91,129.00,128.63,127.26,124.61,81.27,48.08,47.00, 37.71,36.14,29.63,28.98,28.59,27.82,18.51.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C22H27O3S([M+H]+)371.1681,found 371.1683.
Fig. 1 and Fig. 2 is respectively the nuclear magnetic resonance spectroscopy and carbon spectrum of compound 2.
The physicochemical property of compound 3 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.19- 7.20(m,3H,Ar-H),7.01-7.04(m,2H,2-H and Ar-H),6.12-6.19(m,2H,3-H and 5-H), 4.27-4.31 (m, 1H, 8-H), 3.56 (d, J=14.0Hz, 1H, 13-H), 3.03-3.09 (m, 2H, 9-H and 13-H), 2.86-2.91(m,1H,10-H),2.63-2.67(m,1H,7-H),2.33(s,4H,6-H and PhCH 3),2.30(s,3H, 15-H), 2.10-2.16 (m, 1H, 6-H), 2.00-2.02 (m, 1H, 11-H), 1.70-1.75 (m, 1H, 9-H), 1.14 (d, J= 6.0Hz,3H,14-H)；13C NMR(125MHz,CDCl3)δ:198.48,175.90,148.31,144.59,139.10, 138.89,135.02,130.36,129.07,127.64,126.72,124.54,81.23,48.93,46.36,36.18, 33.03,28.93,28.70,27.87,21.34,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C22H27O3S([M+H]+)371.1681,found 371.1685.
The physicochemical property of compound 4 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.30 (d, J=6.5Hz, 2H, Ar-H), 7.13 (d, J=6.5Hz, 2H, Ar-H), 7.04 (d, J=16.0Hz, 1H, 2-H), 6.13- 6.19 (m, 2H, 3-H and 5-H), 4.25-4.30 (m, 1H, 8-H), 3.52 (d, J=14.0Hz, 1H, 13-H), 3.02- 3.06(m,2H,9-Hand 13-H),2.88-2.93(m,1H,10-H),2.60-2.64(m,1H,7-H),2.33(s,4H,6-H and PhCH 3),2.30(s,3H,15-H),2.10-2.15(m,1H,6-H),1.99-2.04(m,1H,11-H),1.70-1.75 (m, 1H, 9-H), 1.14 (d, J=6.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.50,175.94, 148.34,144.59,138.91,137.06,131.46,130.50,130.01,124.55,81.21,48.91,46.29, 36.18,33.72,28.94,28.71,27.86,21.05,18.44.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C22H27O3S([M+H]+)371.1681,found 371.1681.
The physicochemical property of compound 5 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.25 (s,1H,Ar-H),6.98-7.05(m,3H,2-H and Ar-H),6.16-6.19(m,2H,3-H and 5-H),4.26- 4.31 (m, 1H, 8-H), 3.46 (d, J=13.5Hz, 1H, 13-H), 3.00-3.04 (m, 2H, 9-H and 13-H), 2.87- 2.92(m,1H,10-H),2.63-2.65(m,1H,7-H),2.37(s,3H,15-H),2.32-2.35(m,1H,6-H),2.30 (s,6H,Ph(CH 3)2),2.11-2.17(m,1H,6-H),1.96-2.03(m,1H,11-H),1.70-1.75(m,1H,9-H), 1.14 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.50,175.88,148.34,144.60, 138.90,138.55,136.86,131.44,130.76,129.99,127.42,124.56,81.19,48.90,46.35, 36.18,32.78,28.94,28.70,27.84,20.91,20.45,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C23H29O3S([M+H]+)385.1837,found 385.1835.
The physicochemical property of compound 6 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.33 (d, J=6.5Hz, 2H, Ar-H), 7.16 (d, J=6.5Hz, 2H, Ar-H), 7.04 (d, J=16.0Hz, 1H, 2-H), 6.12- 6.19(m,2H,3-H and 5-H),4.25-4.30(m,1H,8-H),3.50-3.53(m,1H,13-H),3.03-3.07(m, 2H,9-H and 13-H),2.87-2.92(m,1H,10-H),2.60-2.65(m,3H,7-H and-CH 2CH3),2.29-2.34 (m,4H,6-H and 15-H),2.09-2.15(m,1H,6-H),1.97-2.03(m,1H,11-H),1.69-1.74(m,1H, 9-H), 1.24 (t, J=6.5Hz, 3H ,-CH2CH 3), 1.14 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3) δ:198.49,175.93,148.35,144.58,143.39,138.91,137.76,130.51,128.83,124.56, 81.22,48.89,46.38,36.19,33.66,28.94,28.70,28.43,27.82,18.43,15.51.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C23H29O3S([M+H]+)385.1837,found 385.1841.
The physicochemical property of compound 7 is as follows:
1) white solid, 49.6-50.5 DEG C of fusing point；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.33 (s, 4H, Ar-H), 7.02 (d, J=16.5Hz, 1H, 2-H), 6.18 (d, J=16.0Hz, 1H, 3-H), 6.11 (d, J= 9.0Hz, 1H, 5-H), 4.30 (t, J=11.0Hz, 1H, 8-H), 3.54 (d, J=14Hz, 1H, 13-H), 3.04-3.08 (m, 2H,9-H and 13-H),2.85-2.90(m,1H,10-H),2.62-2.66(m,1H,7-H),2.31-2.34(m,1H,6- H),2.29(s,3H,15-H),2.09-2.15(m,1H,6-H),1.96-2.03(m,1H,11-H),1.69-1.74(m,1H,9- H),1.31(s,9H,-C(CH 3)3), 1.14 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.47, 175.92,150.23,148.35,144.57,138.90,131.69,130.03,126.30,124.60,81.22,48.88, 46.50,36.19,34.54,33.46,31.26,28.93,28.70,27.75,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C25H33O3S([M+H]+)413.2150,found 413.2151.
The physicochemical property of compound 8 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.36 (d, J=7.0Hz, 1H, Ar-H), 7.25 (d, J=7.5Hz, 1H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.92- 6.94 (m, 1H, Ar-H), 6.89 (d, J=8.0Hz, 1H, Ar-H), 6.14-6.19 (m, 2H, 3-H and 5-H), 4.26- 4.30(m,1H,8-H),3.89(s,3H,-OCH 3), 3.55 (d, J=14.0Hz, 1H, 13-H), 3.02-3.05 (m, 2H, 9-H and 13-H),2.90-2.95(m,1H,10-H),2.62-2.65(m,1H,7-H),2.32-2.34(m,1H,6-H),2.29 (s,3H,15-H),2.10-2.16(m,1H,6-H),2.01-2.08(m,1H,11-H),1.70-1.75(m,1H,9-H),1.14 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.48,175.93,157.97,148.37, 144.54,139.06,131.11,128.42,124.52,123.00,121.22,110.93,81.19,55.84,48.98, 46.46,36.21,31.71,28.97,28.76,27.87,18.46.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C22H27O4S([M+H]+)387.1630,found 387.1629.
The physicochemical property of compound 9 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.43- 7.45 (m, 1H, Ar-H), 7.27-7.29 (m, 1H, Ar-H), 7.07-7.13 (m, 2H, Ar-H), 7.05 (d, J=16.0Hz, 1H,2-H),6.15-6.19(m,2H,3-H and 5-H),4.28-4.32(m,1H,8-H),3.47-3.50(m,1H,13-H), 3.13 (dd, J=13.5,6.5Hz, 1H, 13-H), 3.03-3.04 (m, 1H, 9-H), 2.85-2.90 (m, 1H, 10-H), 2.63- 2.65(m,1H,7-H),2.33-2.35(m,1H,6-H),2.30(s,3H,15-H),2.13-2.18(m,1H,6-H),2.02- 2.08 (m, 1H, 11-H), 1.71-1.76 (m, 1H, 9-H), 1.15 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz, CDCl3)δ:198.49,175.63,148.30,144.65,138.74,132.85,129.39,124.81,124.78, 124.61,116.11,115.93,81.27,48.65,46.67,36.18,32.68,28.96,28.60,27.86,18.44.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24FO3S([M+H]+)375.1430,found 375.1429.
The physicochemical property of compound 10 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.28- 7.30 (m, 1H, Ar-H), 7.15 (d, J=7.5Hz, 1H, Ar-H), 7.09 (d, J=9.0Hz, 1H, Ar-H), 7.04 (d, J= 16.0Hz,1H,2-H),6.90-6.93(m,1H,Ar-H),6.14-6.19(m,2H,3-H and 5-H),4.29-4.33(m, 1H, 8-H), 3.56 (d, J=14.0Hz, 1H, 13-H), 3.13 (dd, J=13.5,7.0Hz, 1H, 13-H), 3.03-3.04 (m, 1H,9-H),2.84-2.89(m,1H,10-H),2.66-2.69(m,1H,7-H),2.33-2.36(m,1H,6-H),2.29(s, 3H,15-H),2.13-2.19(m,1H,6-H),1.96-2.03(m,1H,11-H),1.71-1.76(m,1H,9-H),1.15(d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.44,175.59,148.19,144.76,138.43, 130.58,130.51,124.68,116.08,115.90,113.70,113.54,81.29,48.89,46.37,36.17, 32.56,28.97,28.68,27.86,18.44.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24FO3S([M+H]+)375.1430,found 375.1434.
The physicochemical property of compound 11 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.40 (s,2H,Ar-H),7.02-7.05(m,3H,Ar-H and 2-H),6.16-6.20(m,2H,3-H and 5-H),4.27- 4.32 (m, 1H, 8-H), 3.48 (d, J=14.0Hz, 1H, 13-H), 3.04-3.10 (m, 2H, 9-H and 13-H), 2.83- 2.88(m,1H,10-H),2.61-2.63(m,1H,7-H),2.33-2.35(m,1H,6-H),2.30(s,3H,15-H),2.12- 2.18 (m, 1H, 6-H), 1.98-2.05 (m, 1H, 11-H), 1.71-1.76 (m, 1H, 9-H), 1.15 (d, J=6.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.47,175.72,148.23,144.75,138.51,132.82,132.75, 124.69,116.49,116.32,81.25,48.74,46.44,36.18,34.23,28.97,28.65,27.85,18.46.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24FO3S([M+H]+)375.1430,found 375.1425.
The physicochemical property of compound 12 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.45- 7.48 (m, 1H, Ar-H), 7.06 (d, J=16.0Hz, 1H, 2-H), 6.85-6.88 (m, 2H, Ar-H), 6.17-6.20 (m, 2H, 3-H and 5-H), 4.33 (t, J=11.0Hz, 1H, 8-H), 3.39 (d, J=13.5Hz, 1H, 13-H), 3.05-3.11 (m, 2H,9-H and 13-H),2.84-2.89(m,1H,10-H),2.84-2.89(m,1H,7-H),2.33-2.36(m,1H,6- H),2.30(s,3H,15-H),2.15-2.21(m,1H,6-H),2.03-2.10(m,1H,11-H),1.72-1.77(m,1H,9- ), H 1.16 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.47,175.50,148.25, 144.76,138.51,135.23,124.72,112.28,112.11,104.97,104.77,104.56,81.28,48.44, 46.73,36.18,33.48,28.98,28.56,27.82,18.46.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H23F2O3S([M+H]+)393.1336,found 393.1339.
The physicochemical property of compound 13 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.35 (s, 1H, Ar-H), 7.20-7.25 (m, 3H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.14-6.19 (m, 2H, 3-H And 5-H), 4.29-4.33 (m, 1H, 8-H), 3.54 (d, J=13.5Hz, 1H, 13-H), 3.14 (dd, J=13.5,6.5Hz, 1H,13-H),3.03-3.04(m,1H,9-H),2.81-2.86(m,1H,10-H),2.66-2.68(m,1H,7-H),2.33- 2.36(m,1H,6-H),2.29(s,3H,15-H),2.13-2.19(m,1H,6-H),1.96-2.03(m,1H,11-H),1.70- 1.75 (m, 1H, 9-H), 1.15 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.44,175.56, 148.20,144.77,138.43,137.62,134.97,130.26,128.98,127.33,126.81,124.69,81.29, 48.78,46.42,36.16,32.65,28.96,28.64,27.84,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24ClO3S([M+H]+)391.1135,found 391.1141.
The physicochemical property of compound 14 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.27- 7.33 (m, 4H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.14-6.19 (m, 2H, 3-H and 5-H), 4.27- 4.32 (m, 1H, 8-H), 3.53 (dd, J=14.0,4.0Hz, 1H, 13-H), 3.10 (dd, J=14.0,7.5Hz, 1H, 13-H), 3.01-3.05(m,1H,9-H),2.82-2.88(m,1H,10-H),2.61-2.66(m,1H,7-H),2.32-2.36(m,1H, 6-H),2.30(s,3H,15-H),2.12-2.18(m,1H,6-H),1.96-2.03(m,1H,11-H),1.70-1.75(m,1H, 9-H), 1.15 (d, J=7.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.48,175.65,148.22, 144.78,138.43,133.88,132.91,131.12,129.40,124.75,81.29,48.85,46.38,36.19, 33.23,28.98,28.66,27.82,18.46.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24ClO3S([M+H]+)391.1135,found 391.1133.
Fig. 3 and Fig. 4 is respectively the nuclear magnetic resonance spectroscopy and carbon spectrum of compound 14.
The physicochemical property of compound 15 is as follows:
1) white solid, 50.6-50.9 DEG C of fusing point；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.42 (s, 1H, Ar-H), 7.34 (d, J=7.5Hz, 1H, Ar-H), 7.25 (d, J=8.0Hz, 1H, Ar-H), 7.05 (d, J= 16.0Hz, 1H, 2-H), 6.17-6.20 (m, 2H, 3-H and 5-H), 4.30-4.35 (m, 1H, 8-H), 3.54 (d, J= 13.5Hz,1H,13-H),3.06-3.10(m,2H,9-H and 13-H),2.87-2.92(m,1H,10-H),2.66-2.69 (m,1H,7-H),2.34-2.37(m,1H,6-H),2.30(s,3H,15-H),2.16-2.22(m,1H,6-H),1.99-2.05 (m, 1H, 11-H), 1.72-1.77 (m, 1H, 9-H), 1.16 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3) δ:198.47,175.47,148.20,144.77,138.38,135.11,133.29,132.94,130.54,129.84, 127.74,124.77,81.36,49.05,46.23,36.15,32.19,28.95,28.69,27.79,18.45.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H23Cl2O3S([M+H]+)425.0745,found 425.0745.
The physicochemical property of compound 16 is as follows:
1) white solid, 51.8-52.5 DEG C of fusing point；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.58 (d, J=7.5Hz, 1H, Ar-H), 7.38 (d, J=7.0Hz, 1H, Ar-H), 7.29-7.32 (m, 1H, Ar-H), 7.07-7.10 (m, 1H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.16-6.19 (m, 2H, 3-H and 5-H), 4.30-4.34 (m, 1H, 8-H), 3.60 (d, J=13.5Hz, 1H, 13-H), 3.05-3.10 (m, 2H, 9-H and 13-H), 2.92-2.97 (m, 1H,10-H),2.67-2.71(m,1H,7-H),2.33-2.36(m,1H,6-H),2.30(s,3H,15-H),2.15-2.20(m, 1H, 6-H), 1.99-2.06 (m, 1H, 11-H), 1.73-1.78 (m, 1H, 9-H), 1.15 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.49,175.67,148.28,144.66,138.68,136.65,133.33,129.18, 128.08,127.56,124.66,124.37,81.36,49.24,46.12,36.15,32.51,28.95,28.78,27.82, 18.44.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24BrO3S([M+H]+)435.0630,found 435.0623.
The physicochemical property of compound 17 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.50 (s, 1H, Ar-H), 7.36 (d, J=7.5Hz, 1H, Ar-H), 7.31 (d, J=7.5Hz, 1H, Ar-H), 7.16-7.19 (m, 1H, ), Ar-H 7.05 (d, J=16.0Hz, 1H, 2-H), 6.14-6.19 (m, 2H, 3-H and 5-H), 4.29-4.33 (m, 1H, 8- ), H 3.53 (d, J=14.0Hz, 1H, 13-H), 3.14 (dd, J=13.5,7.0Hz, 1H, 13-H), 3.03-3.04 (m, 1H, 9- H),2.80-2.85(m,1H,10-H),2.66-2.68(m,1H,7-H),2.33-2.36(m,1H,6-H),2.30(s,3H,15- ), H 2.13-2.19 (m, 1H, 6-H), 1.96-2.03 (m, 1H, 11-H), 1.70-1.75 (m, 1H, 9-H), 1.15 (d, J= 7.0Hz,3H,14-H)；13C NMR(125MHz,CDCl3)δ:198.45,175.55,148.21,144.77,138.43, 137.94,131.82,130.53,129.72,127.84,124.70,123.04,81.30,48.74,46.45,36.17, 32.69,28.96,28.63,27.84,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24BrO3S([M+H]+)435.0630,found 435.0628.
The physicochemical property of compound 18 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.44 (d, J=7.0Hz, 2H, Ar-H), 7.25-7.26 (d, J=7.0Hz, 2H, Ar-H), 7.05 (d, J=16.0Hz, 1H, 2-H), 6.13-6.19 (m, 2H, 3-H and 5-H), 4.27-4.32 (m, 1H, 8-H), 3.53 (d, J=14.0Hz, 1H, 13-H), 3.03-3.10(m,2H,9-H and 13-H),2.82-2.87(m,1H,10-H),2.63-2.65(m,1H,7-H),2.33- 2.35(m,1H,6-H),2.30(s,3H,15-H),2.12-2.17(m,1H,6-H),1.95-2.02(m,1H,11-H),1.70- 1.75 (m, 1H, 9-H), 1.15 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.48,175.63, 148.22,144.76,138.43,134.58,132.30,131.23,124.74,120.72,81.28,48.83,46.35, 36.17,32.99,28.95,28.63,27.81,18.44.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C21H24BrO3S([M+H]+)435.0630,found 435.0630.
The physicochemical property of compound 19 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.78- 7.81 (m, 3H, Ar-H), 7.75 (d, J=7.0Hz, 1H, Ar-H), 7.45-7.50 (m, 3H, Ar-H), 6.93 (d, J= 16.0Hz, 1H, 2-H), 6.15 (d, J=16.0Hz, 1H, 3-H), 6.00 (d, J=9.0Hz, 1H, 5-H), 4.24-4.29 (m, 1H, 8-H), 3.67 (d, J=14.0Hz, 1H, 13-H), 3.20 (dd, J=14.0,7.0Hz, 1H, 13-H), 2.99-3.01 (m, 1H,9-H),2.82-2.87(m,1H,10-H),2.67-2.71(m,1H,7-H),2.31-2.34(m,1H,6-H),2.28(s, 3H, 15-H), 2.00-2.13 (m, 2H, 6-H and 11-H), 1.69-1.73 (m, 1H, 9-H), 1.11 (d, J=6.5Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.46,175.85,148.28,144.58,138.73,133.75,132.72, 132.03,128.91,127.88,127.76,127.45,127.17,126.83 126.14,124.59,81.25,48.88, 46.37,36.17,32.80,28.91,28.60,27.75,18.38.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C25H27O3S([M+H]+)407.1681,found 407.1681.
The physicochemical property of compound 20 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.07 (d, J=16.0Hz, 1H, 2-H), 6.25 (d, J=8.5Hz, 1H, 5-H), 6.20 (d, J=16.0Hz, 1H, 3-H), 4.31- 4.36(m,1H,8-H),4.11-4.13(m,1H),3.97-4.00(m,1H),3.73-3.76(m,1H),3.37-3.38(m, 1H),3.02-3.05(m,2H),2.81-2.86(m,2H),2.64-2.66(m,1H),2.34-2.37(m,1H,6-H),2.30 (s,3H,15-H),2.17-2.23(m,1H,6-H),1.98-2.07(m,2H),1.74-1.79(m,1H),1.25-1.29(m, 4H), 1.17 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.49,175.94,148.36, 144.73,138.60,124.71,81.38,77.11,65.96,49.38,48.12,47.34,36.16,33.83,30.33, 29.00,28.65,27.78,18.52,16.95.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C20H29O4S([M+H]+)365.1787,found 365.1789.
The physicochemical property of compound 21 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.30 (s, 1H, Ar-H), 7.07 (d, J=16.0Hz, 1H, 2-H), 6.36 (s 1H, Ar-H), 6.17-6.20 (m, 2H, 3-H and 5-H), 4.28-4.32 (m, 1H, 8-H), 3.17 (d, J=14.0Hz, 1H, 13-H), 3.05-3.06 (m, 1H, 9-H), 2.95 (dd, J=13.5,6.0Hz, 1H, 13-H), 2.80-2.85 (m, 1H, 10-H), 2.56-2.58 (m, 1H, 7-H), 2.36-2.32 (m,4H,6-H andArCH3),2.30(s,3H,15-H),2.12-2.17(m,1H,6-H),2.04-2.09(m,1H,11-H), 1.71-1.76 (m, 1H, 9-H), 1.16 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.47, 175.77,154.57,148.24,144.76,141.09,138.69,124.65,114.32,110.09,81.15,48.20, 46.67,36.21,34.38,29.00,28.57,27.88,18.44,11.96.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C20H25O4S([M+H]+)361.1474,found 361.1473.
The physicochemical property of compound 22 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:8.40 (s, 1H, Ar-H), 7.47-7.49 (m, 1H, Ar-H), 7.20 (d, J=7.5Hz, 1H, Ar-H), 6.97-7.01 (m, 2H, 2-H ), andAr-H 6.12-6.16 (m, 2H, 3-H and 5-H), 4.29-4.33 (m, 1H, 8-H), 3.82 (d, J=14.0Hz, 1H, 13-H), 3.45 (d, J=14.0Hz, 1H, 13-H), 2.98-3.02 (m, 2H), 2.82-2.85 (m, 1H), 2.30-2.32 (m, 1H,6-H),2.27(s,3H,15-H),2.12-2.18(m,1H,6-H),1.90-1.96(m,1H,11-H),1.66-1.71(m, 1H, 9-H), 1.14 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.46,176.32,157.87, 149.12,148.41,144.57,139.35,136.14,124.27,122.41,119.81,81.39,47.50,47.43, 36.11,28.99,28.63,27.98,26.93,18.41.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C20H24NO3S([M+H]+)358.1477,found 358.1473.
Fig. 5 and Fig. 6 is respectively the nuclear magnetic resonance spectroscopy and carbon spectrum of compound 22.
The physicochemical property of compound 23 is as follows:
1) weak yellow liquid；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:8.44 (s, 2H, Ar-H), 7.18 (s, 2H, Ar-H), 7.04 (d, J=16.0Hz, 1H, 2-H), 6.17-6.19 (m, 2H, 3-H and 5-H), 4.32-4.37 (m, 1H, 8-H), 3.63 (d, J=13.5Hz, 1H, 13-H), 3.15 (dd, J=13.5,7.5Hz, 1H, 13-H),3.04-3.05(m,1H,9-H),2.85-2.90(m,1H,10-H),2.72-2.73(m,1H,7-H),2.34-2.37 (m,1H,6-H),2.29(s,3H,15-H),2.19-2.25(m,1H,6-H),1.95-2.02(m,1H,11-H),1.72-1.77 (m, 1H, 9-H), 1.16 (d, J=7.0Hz, 3H, 14-H)；13C NMR(125MHz,CDCl3)δ:198.41,175.33, 149.55,148.05,147.61,144.90,138.00,124.82,120.94,81.38,49.18,46.14,36.11, 29.65,28.95,28.68,27.84,18.43.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C20H24NO3S([M+H]+)358.1477,found 358.1476.
The following are the synthetic routes of compound 24:
It takes a certain amount of Xanthatin to be dissolved in methanol, triethylamine is added after 10min is stirred at room temperature, is slow added into 2- The methanol solution of mercaptobenzothiazoler is subsequently moved in 55 DEG C of oil baths, TLC tracing detection, after reaction, is concentrated under reduced pressure, system Standby silica gel thin-layer chromatography separation obtains target product.
Reaction formula is as follows:
The physicochemical property of compound 24 is as follows:
1) white solid, 200.6-201.1 DEG C of fusing point；
2) the nuclear magnetic resonance figures spectrum signature of the compound:
Using deuterated chloroform as solvent, TMS is internal standard, wherein each peak belongs to are as follows:1H NMR(500MHz,CDCl3)δ:7.52 (d, J=7.5Hz, 1H, Ar-H), 7.42-7.47 (m, 2H, Ar-H), 7.33-7.36 (m, 1H, Ar-H), 7.03 (d, J= 16.0Hz, 1H, 2-H), 6.13-6.16 (m, 2H, 3-H and 5-H), 5.07 (dd, J=14.5,8.0Hz, 1H, 13-H), 4.61 (d, J=14.5Hz, 1H, 13-H), 4.30-4.34 (m, 1H, 8-H), 3.11-3.14 (m, 1H, 9-H), 3.03-3.04 (m,1H,7-H),2.60-2.65(m,1H,10-H),2.33-2.36(m,1H,6-H),2.28(s,3H,15-H),2.17-2.24 (m, 1H, 11-H), 2.02-2.07 (m, 1H, 6-H), 1.73-1.78 (m, 1H, 9-H), 1.12 (d, J=7.0Hz, 3H, 14-H) ；13C NMR(125MHz,CDCl3)δ:198.59,189.82,175.26,148.38,144.57,141.23,138.75, 127.39,127.34,125.24,124.81,121.51,112.75,81.89,48.90,45.49,45.43,36.04, 28.86,28.44,27.51,18.32.
3) the high resolution mass spectrum feature of the compound:
Using electrospray ionisation: calcd for C22H23NO3S2Na([M+Na]+)436.1017,found 436.1009.
Biological activity determination test of the invention:
1, test plant disease fungus: tomato early blight bacterium (Alternaria solani), Beancurd sheet reaping hook germ (Fusariumsolani), botrytis cinerea (Botrytis cinerea), cucumber anthracnose (Colletrichum orbiculare)；For trying insect: two latter stage in age diamondback moth larvaes (Plutella xylostella)
2, for reagent product and reagent:
Sample are as follows: Xanthatin analog derivative 1-24 and positive control medicament phenylate prepared by raw material Xanthatin, embodiment Methyl cyclic-azole (98%), hymexazol (99%) and toosendanin (> 98%)；Solvent is DMSO (chromatographically pure), acetone (analysis pure), emulsification Agent is Tween-80 (excellent pure grade).
3, sod cultivation:
Antibacterial activity is using inhibition spore germination method:
(1) preparation of spore suspension: 2 weeks are cultivated by pathogen at 25 ± 1 DEG C, in PDA culture medium, then scraper Bacterium colony is gently scraped, aseptic water washing, double gauze is filtered to remove mycelia and culture medium, and sterile water washs 3 times repeatedly, finally It is diluted to required spore concentration with sterile water (under 100 power microscopes, the about 20-40 spore of each visual field).
(2) medicament is prepared: sample to be tested being dissolved in a certain amount of DMSO, with 0.1% Tween-80 aseptic aqueous solution 5-7 series mass concentration is arranged further according to agent activity in dilution preparation 1mg/mL stoste, and the final content of organic solvent does not surpass Cross 2% (v/v).
(3) chemicals treatment: prepared sample solution is uniformly mixed with spore suspension in equal volume obtain it is required most Final concentration.As a control group with the Tween-80 aseptic aqueous solution of 2%DMSO plus 0.1%.Above-mentioned mixing is drawn with micro sample adding appliance Drop is put in the culture dish with shallow seated groundwater in concave slide, and capping, which is placed in the incubator of preference temperature, cultivates.It is micro- The sprouting situation of spore on microscopic observation glass slide.When germ tube after spore germination is greater than spore minor axis, as sprouts, work as sky When the spore germination rate of white control is greater than 90%, the spore germination rate (formula 1) of each processing group is observed and calculates, while using public Formula 2 calculates the correction inhibition of germination of each processing group, and finds out the IC of each compound50, 95% confidence interval etc., measurement It the results are shown in Table 1.
Spore germination rate=sprouting spore count/statistics spore sum × 100% (formula 1)；
Correction inhibition of germination=(control group be averaged spore germination rate-processing group be averaged spore germination rate)/compares The average spore of group
Sub- germination rate × 100% (formula 2).
1 Xanthatin thioether class (1-23 in table) of table and imines (24 in table) derivative are to Four Plants disease fungus spore Inhibiting germination effect
Conclusion:
It is sprouted the result shows that all test compounds prepared by the present invention show good inhibition to tomato early epidemic spore Breaking-out is used；All spore Inhibiting germination activity for trying strain of compound 22 and 23 pair are above the spore germination being commercialized and press down Preparation hymexazol and difenoconazole show stronger inhibition fungus spore germination effect；Compound 6 is to wherein 3 kinds for examination Strain (except tomato early blight bacterium) inhibits spore germination activity to be above difenoconazole and hymexazol；Compound 24 is to wherein 3 kinds inhibit spore germination activity to be above difenoconazole and hymexazol for examination strain (except cucumber anthracnose)；In addition, changing It closes object 6 and 10 pair botrytis cinerea spore and shows strong Inhibiting germination effect, it is right much higher than substrate Xanthatin and the positive According to medicament hymexazol and difenoconazole.Therefore a series of Xanthatin thioether classes of the present invention and imines analog derivative are expected to use In being prepared into efficient novel plant source spore germination inhibitor.
Stomach poison activity uses leaflet dish additive process:
One layer of filter paper is spread in the culture dish bottom that diameter is 6cm, and the development of every 20 head growth of ware picking is consistent, healthy and strong active Two latter stage in age diamondback moth larvaes.The compound 1-24 of a certain amount of toosendanin, Xanthatin and embodiment preparation is weighed respectively, it is molten The medical fluid that concentration is 20mg/mL is made into acetone.Cabbage leaves are broken into the leaflet dish that diameter is 1cm with punch, with micro point Sample device draws the front and back sides that 2 μ L medical fluids are uniformly applied to leaflet dish, feeds test worm after natural drying.Using acetone as blank control Group.Every processing is repeated 3 times.It is cultivated under conditions of temperature is 25 ± 1 DEG C, humidity 65%-80%, light application time are 12h/12h. Normal leaf dish is fed after 48h until pupating.Periodically (feed normal leaf dish rise for 24 hours, 48h and 72h) record test worm death toll, Poisoning symptom etc., according to 3 calculation processing of formula after different time sections test worm the death rate and corrected mortality (formula 4).Measurement result is shown in Table 2.
The death rate=dead total borer population × 100% of borer population/processing (formula 3)；
Corrected mortality=(processing group average mortality-control group average mortality)/(1- control group average mortality) × 100% (formula 4).
2 Xanthatin thioether class (1-23 in table) of table and imines (24 in table) derivative are to two latter stage in age diamondback moth larvaes Stomach poison activity effect
Conclusion:
The result shows that with Xanthatin thioether class of the present invention and imines analog derivative feeding 2 latter stage in age diamondback moth children Worm, from after feeding band poison leaf dish for 24 hours when, the corrected mortality of compound 3 has been higher than comparison medicament toosendanin；When 72h The corrected mortality of compound 1,5,14 and 15 is more than or close to toosendanin.Therefore, Xanthatin thioether class of the invention Preparation is expected to be used for efficiently with imines analog derivative, less toxic plant insecticide.

Claims (5)

1. Xanthatin thioether class and imines analog derivative, which is characterized in that chemical general formula are as follows:
R in chemical general formula is respectively below any:
2. the preparation method of Xanthatin thioether class and imines analog derivative according to claim 1, which is characterized in that with three Ethamine is base, methanol is solvent, makes Xanthatin that Michael addition reaction occur from different mercaptan/thiophenol, obtains Xanthatin Thioether class and imines analog derivative.
3. the preparation method of Xanthatin thioether class and imines analog derivative according to claim 2, which is characterized in that including Following steps:
(1) it takes a certain amount of Xanthatin to be dissolved in methanol, 1-2 drop triethylamine is added after 10min is stirred at 0-5 DEG C；
(2) it is slow added into corresponding mercaptan/thiophenol methanol solution, TLC tracing detection is concentrated under reduced pressure after reaction, system Standby silica gel thin-layer chromatography separates to obtain required target product.
4. the preparation method of Xanthatin thioether class and imines analog derivative according to claim 2 or 3, which is characterized in that Mercaptan/the thiophenol is following any:
Cyclohexylmercaptan, benzyl mercaptan, 3- methylbenzene phenyl-sulfhydrate, toluene-ω-thiol, 2,4- thiophenol dimethyl benzene, 4- ethyl thiophenol, 4- Tert .- butylthiophenol, 2- methoxybenzenethiol, 2- fluoro thiophenol, 3- fluoro thiophenol, 4- fluoro thiophenol, 2,4 difluorobenzene thiophenol, 3- chlorothio-phenol, 4- chlorothio-phenol, 2,4 dichloro benzene thiophenol, 2- bromo thiophenol, 3- bromo thiophenol, 4- bromo thiophenol, 2- naphthalene sulphur Phenol, 2- methyltetrahydrofuran -3- mercaptan, 2- methyl -3- furanthiol, 2- mercaptopyridine, 4- mercaptopyridine, 2- sulfydryl benzo thiophene Azoles.
5. the application of Xanthatin thioether class and imines analog derivative according to claim 1, which is characterized in that be used to prepare Plant-source antibacterial agent/insecticide.
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