CN112341506A - Acetyl glucose thiadiazole benzamide compound and synthesis method and application thereof - Google Patents
Acetyl glucose thiadiazole benzamide compound and synthesis method and application thereof Download PDFInfo
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- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims abstract description 15
- HXBYBCASAVUYKF-GVYWOMJSSA-N (4r,5s,6r,7r)-4,5,6,7,8-pentahydroxyoctane-2,3-dione Chemical compound CC(=O)C(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO HXBYBCASAVUYKF-GVYWOMJSSA-N 0.000 title claims abstract description 14
- 238000001308 synthesis method Methods 0.000 title abstract description 14
- 150000001875 compounds Chemical class 0.000 title abstract description 13
- 241000233622 Phytophthora infestans Species 0.000 claims abstract description 12
- 230000001717 pathogenic effect Effects 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- 239000002994 raw material Substances 0.000 claims description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- -1 acetylglucos thiadiazole benzamide compound Chemical class 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 239000011259 mixed solution Substances 0.000 claims description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000012153 distilled water Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 244000052769 pathogen Species 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 239000003899 bactericide agent Substances 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 230000005764 inhibitory process Effects 0.000 abstract description 4
- 235000002595 Solanum tuberosum Nutrition 0.000 abstract description 2
- 244000061456 Solanum tuberosum Species 0.000 abstract description 2
- 230000001954 sterilising effect Effects 0.000 abstract description 2
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 2
- 235000013361 beverage Nutrition 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- PWWSSIYVTQUJQQ-UHFFFAOYSA-N distearyl thiodipropionate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCCCCCCCC PWWSSIYVTQUJQQ-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- GDGIVSREGUOIJZ-UHFFFAOYSA-N 5-amino-3h-1,3,4-thiadiazole-2-thione Chemical compound NC1=NN=C(S)S1 GDGIVSREGUOIJZ-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- XERJKGMBORTKEO-VZUCSPMQSA-N (1e)-2-(ethylcarbamoylamino)-n-methoxy-2-oxoethanimidoyl cyanide Chemical compound CCNC(=O)NC(=O)C(\C#N)=N\OC XERJKGMBORTKEO-VZUCSPMQSA-N 0.000 description 1
- QNBTYORWCCMPQP-JXAWBTAJSA-N (Z)-dimethomorph Chemical compound C1=C(OC)C(OC)=CC=C1C(\C=1C=CC(Cl)=CC=1)=C/C(=O)N1CCOCC1 QNBTYORWCCMPQP-JXAWBTAJSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QYPADGBLSFJOOE-SWPSLBAPSA-N C(C1=CC=CC=C1)(=O)N.S1N=NC=C1.C(C)(=O)[C@@](C(=O)Br)(O)[C@@H](O)[C@H](O)[C@H](O)CO Chemical class C(C1=CC=CC=C1)(=O)N.S1N=NC=C1.C(C)(=O)[C@@](C(=O)Br)(O)[C@@H](O)[C@H](O)[C@H](O)CO QYPADGBLSFJOOE-SWPSLBAPSA-N 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- 239000005747 Chlorothalonil Substances 0.000 description 1
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 1
- 239000005750 Copper hydroxide Substances 0.000 description 1
- 239000005754 Cyazofamid Substances 0.000 description 1
- 239000005756 Cymoxanil Substances 0.000 description 1
- 239000005761 Dimethomorph Substances 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- 239000005782 Fluopicolide Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000005867 Iprodione Substances 0.000 description 1
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 description 1
- 239000005802 Mancozeb Substances 0.000 description 1
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 description 1
- 239000005807 Metalaxyl Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000005821 Propamocarb Substances 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 1
- 229910001956 copper hydroxide Inorganic materials 0.000 description 1
- YXKMMRDKEKCERS-UHFFFAOYSA-N cyazofamid Chemical compound CN(C)S(=O)(=O)N1C(C#N)=NC(Cl)=C1C1=CC=C(C)C=C1 YXKMMRDKEKCERS-UHFFFAOYSA-N 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- BFWMWWXRWVJXSE-UHFFFAOYSA-M fentin hydroxide Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(O)C1=CC=CC=C1 BFWMWWXRWVJXSE-UHFFFAOYSA-M 0.000 description 1
- GBOYJIHYACSLGN-UHFFFAOYSA-N fluopicolide Chemical compound ClC1=CC(C(F)(F)F)=CN=C1CNC(=O)C1=C(Cl)C=CC=C1Cl GBOYJIHYACSLGN-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- ONUFESLQCSAYKA-UHFFFAOYSA-N iprodione Chemical compound O=C1N(C(=O)NC(C)C)CC(=O)N1C1=CC(Cl)=CC(Cl)=C1 ONUFESLQCSAYKA-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229930014456 matrine Natural products 0.000 description 1
- ZQEIXNIJLIKNTD-UHFFFAOYSA-N methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alaninate Chemical compound COCC(=O)N(C(C)C(=O)OC)C1=C(C)C=CC=C1C ZQEIXNIJLIKNTD-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001965 potato dextrose agar Substances 0.000 description 1
- WZZLDXDUQPOXNW-UHFFFAOYSA-N propamocarb Chemical compound CCCOC(=O)NCCCN(C)C WZZLDXDUQPOXNW-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
-
- 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
- A01N43/82—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 three ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses an acetyl glucose thiadiazole benzamide compound and a synthesis method and application thereof, belonging to the technical field of chemical synthesis, wherein the structural general formula of the acetyl glucose thiadiazole benzamide compound is as follows:
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to an acetyl glucose thiadiazole benzamide compound and a synthesis method and application thereof.
Background
The potato late blight is a destructive disease caused by phytophthora infestans, has the characteristics of wide occurrence range, high epidemic speed and serious harm, can reduce the yield by 10-20% in general years, can reach 50-70% in serious harm years, and even cannot be harvested. At present, due to the degeneration of disease resistance of varieties and imperfect agricultural management, the prevention and treatment of the potato late blight mainly depends on chemical prevention and treatment. The medicaments for preventing and treating potato late blight mainly comprise protective medicaments such as copper hydroxide, mancozeb, fentin, iprodione, chlorothalonil, fluopicolide, cyazofamid and the like; propamocarb, metalaxyl, cymoxanil, dimethomorph and other therapeutic agents, and matrine, eugenol and other biological source bactericides. However, the use of these chemicals for controlling potato late blight brings about problems such as: the long-term use of the traditional chemical pesticide can lead pathogens to gradually generate resistance, and the use amount of the pesticide is continuously increased, thus leading the problem of more serious ecological environment; and most of the traditional chemical bactericides kill pathogenic bacteria and poison beneficial microorganisms and natural enemies of insects and pests.
Therefore, creating a novel, efficient and environmentally friendly bactericide is a real problem that needs to be solved urgently in the current agricultural production.
Disclosure of Invention
The embodiment of the invention aims to provide an acetyl glucose thiadiazole benzamide compound so as to solve the problems in the background technology.
In order to achieve the above purpose, the embodiments of the present invention provide the following technical solutions:
an acetyl glucose thiadiazole benzamide compound has a structural general formula as shown in formula I:
wherein R is a substituent at any position on the ring.
Preferably, in the formula, R is H or 2-CH3、3-CH3、4-CH3、2-OCH3、3-OCH3、4-OCH3、2,3-(CH3)2、2,4-(CH3)2、2,5-(CH3)2、2,6-(CH3)2、2,3-(OCH3)2、2,4-(OCH3)2、2,5-(OCH3)2、2,6-(OCH3)2、2-F、3-F、4-F、2-Cl、3-Cl、4-Cl、2-Br、3-Br、4-BrPh、2-NO2、3-NO2、4-NO2、2-CF3、3-CF3、4-CF3At least one of (1).
Another objective of the embodiments of the present invention is to provide a method for synthesizing the aforementioned acetylglucose thiadiazole benzamide compound, which comprises the following steps:
reacting the raw material A with the raw material B to obtain an intermediate C;
reacting the intermediate C with a raw material D to obtain the acetylglucose thiadiazole benzamide compound;
the structural formulas of the raw material A, the raw material B, the intermediate C and the raw material D are respectively shown as a formula A, a formula B, a formula C and a formula D:
preferably, the step of reacting the raw material a with the raw material B to obtain the intermediate C specifically includes:
mixing B, NaOH raw materials, distilled water and acetone to obtain a first mixed solution;
and preparing the raw material A into a solution, dropwise adding the solution into the first mixed solution for reaction, and then purifying and separating to obtain an intermediate C.
Preferably, in the step, the raw material A is prepared into an acetone solution of the raw material A.
Preferably, the step of reacting the intermediate C with the raw material D to obtain the acetylglucose thiadiazole benzamide compound specifically includes:
mixing the intermediate C, dichloromethane and triethylamine to obtain a second mixed solution;
and (3) mixing the raw material D with thionyl chloride, reacting completely, removing the thionyl chloride, preparing the residue into triethylamine solution, dropwise adding the triethylamine solution into the second mixed solution, reacting, and purifying and separating to obtain the acetylglucose thiadiazole benzamide compound.
Preferably, in this step, the residue is formulated as a solution of the acid chloride in methylene chloride.
Specifically, the reaction route of the synthesis method is as follows:
the embodiment of the invention also aims to provide application of the acetylglucose thiadiazole benzamide compound in inhibiting potato late blight pathogenic bacteria.
Compared with the prior art, the embodiment of the invention has the beneficial effects that:
the acetyl glucose thiadiazole benzamide compound provided by the embodiment of the invention is simple in synthesis method, is an efficient and environment-friendly bactericide, can be applied to agricultural sterilization, particularly has a good inhibition effect on the activity of potato late blight pathogenic bacteria, and can be used for preventing and reducing the occurrence of potato late blight.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Example 1
The material embodiment provides a synthesis method of an acetyl glucose thiadiazole benzamide compound, and the reaction route is as follows, wherein R is a substituent on a ring where R is located, and is specifically 4-CH3：
Specifically, the synthesis method comprises the following steps:
s1, synthesis of intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl- β -D-glucose): adding 400mg (0.01mol) of NaOH, 10mL of distilled water, 50mL of acetone solution and 1.33g (0.01mol) of 2-amino-5-mercapto-1, 3, 4-thiadiazole into a 50mL three-necked bottle, and stirring for 30min to obtain a first mixed solution; 0.98g (2.4mmo1) of 2 ', 3', 4 ', 6' -tetra-O-acetyl-. alpha. -D-bromoglucose was dissolved in 5mL of acetone solution and added dropwise to the first mixed solution to conduct a reaction, stirred at room temperature, checked by TLC, developing solvent: v (ethyl acetate): v (petroleum ether) ═ 1: 2. When the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, 200mL of dichloromethane were added to the bottle containing the residue, washed 2 times with water (2X 20mL), the aqueous phase was extracted 2 times with dichloromethane (2X 20mL), and the organic phases were combined. Drying the organic phase by anhydrous magnesium sulfate, filtering, decompressing, spin-drying and removing the solvent to obtain a crude product, and separating by silica gel column chromatography to obtain an intermediate (2-amino-5- (sulfo-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose).
S2, dissolving 2.54mmol (0.345g) of raw material D with the structural formula of the following formula D in 4 mL of thionyl chloride in a 50mL three-neck flask, carrying out reflux reaction at 60 ℃ for 2 hours, fully spin-drying a reaction system, adding 1.0mmol of the intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose), 10mL of dichloromethane and triethylamine (TEA, 1.0mmol), stirring at room temperature, slowly dropwise adding a dichloromethane solution of 1.2mmol of acyl chloride, stirring for three hours, carrying out TLC tracking reaction, after the reaction is completed, quenching with water, separating out an organic phase, spin-drying, and recrystallizing a crude product with isopropanol to obtain the acetylglucose thiadiazole benzamide compound. Wherein the structural formula of the raw material D is as follows:
example 2
The material embodiment provides a synthesis method of an acetyl glucose thiadiazole benzamide compound, which has the following reaction route, wherein R is a substituent on a ring where the R is located, and specifically is 4-F:
specifically, the synthesis method comprises the following steps:
s1, synthesis of intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl- β -D-glucose): adding 400mg (0.01mol) of NaOH, 10mL of distilled water, 50mL of acetone solution and 1.33g (0.01mol) of 2-amino-5-mercapto-1, 3, 4-thiadiazole into a 50mL three-necked bottle, and stirring for 30min to obtain a first mixed solution; 0.98g (2.4mmo1) of 2 ', 3', 4 ', 6' -tetra-O-acetyl-. alpha. -D-bromoglucose was dissolved in 5mL of acetone solution and added dropwise to the first mixed solution to conduct a reaction, stirred at room temperature, checked by TLC, developing solvent: v (ethyl acetate): v (petroleum ether) ═ 1: 2. When the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, 200mL of dichloromethane were added to the bottle containing the residue, washed 2 times with water (2X 20mL), the aqueous phase was extracted 2 times with dichloromethane (2X 20mL), and the organic phases were combined. Drying the organic phase by anhydrous magnesium sulfate, filtering, decompressing, spin-drying and removing the solvent to obtain a crude product, and separating by silica gel column chromatography to obtain an intermediate (2-amino-5- (sulfo-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose).
S2, dissolving 2.54mmol (0.355g) of raw material D with the structural formula shown as the following formula D in 4 mL of thionyl chloride in a 50mL three-neck flask, carrying out reflux reaction at 60 ℃ for 2 hours, fully spin-drying a reaction system, adding 1.0mmol of the intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose), 10mL of dichloromethane and triethylamine (TEA, 1.0mmol), stirring at room temperature, slowly dropwise adding a dichloromethane solution of 1.2mmol of acyl chloride, stirring for three hours, carrying out TLC tracking reaction, after the reaction is completed, quenching with water, separating out an organic phase, spin-drying, and recrystallizing a crude product with isopropanol to obtain the acetylglucose thiadiazole benzamide compound. Wherein the structural formula of the raw material D is as follows:
example 3
The material embodiment provides a synthesis method of an acetyl glucose thiadiazole benzamide compound, which has the following reaction route, wherein R is a substituent on a ring where the R is located, and is specifically 4-Br:
specifically, the synthesis method comprises the following steps:
s1, synthesis of intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl- β -D-glucose): adding 400mg (0.01mol) of NaOH, 10mL of distilled water, 50mL of acetone solution and 1.33g (0.01mol) of 2-amino-5-mercapto-1, 3, 4-thiadiazole into a 50mL three-necked bottle, and stirring for 30min to obtain a first mixed solution; 0.98g (2.4mmo1) of 2 ', 3', 4 ', 6' -tetra-O-acetyl-. alpha. -D-bromoglucose was dissolved in 5mL of acetone solution and added dropwise to the first mixed solution to conduct a reaction, stirred at room temperature, checked by TLC, developing solvent: v (ethyl acetate): v (petroleum ether) ═ 1: 2. When the reaction was complete, the solvent was removed by rotary evaporation under reduced pressure, 200mL of dichloromethane were added to the bottle containing the residue, washed 2 times with water (2X 20mL), the aqueous phase was extracted 2 times with dichloromethane (2X 20mL), and the organic phases were combined. Drying the organic phase by anhydrous magnesium sulfate, filtering, decompressing, spin-drying and removing the solvent to obtain a crude product, and separating by silica gel column chromatography to obtain an intermediate (2-amino-5- (sulfo-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose).
S2, dissolving 2.54mmol (0.508g) of raw material D with the structural formula shown as the following formula D in 4 mL of thionyl chloride in a 50mL three-neck flask, carrying out reflux reaction at 60 ℃ for 2 hours, fully spin-drying a reaction system, adding 1.0mmol of the intermediate (2-amino-5- (thio-1, 3, 4-thiadiazolyl) -2 ', 3', 4 ', 6' -tetra-O-acetyl-beta-D-glucose), 10mL of dichloromethane and triethylamine (TEA, 1.0mmol), stirring at room temperature, slowly dropwise adding a dichloromethane solution of 1.2mmol of acyl chloride, stirring for three hours, carrying out TLC tracking reaction, after the reaction is completed, quenching with water, separating out an organic phase, spin-drying, and recrystallizing a crude product with isopropanol to obtain the acetylglucose thiadiazole benzamide compound. Wherein the structural formula of the raw material D is as follows:
the synthesis of the acetyl bromo-glucose thiadiazole benzamide compounds containing different R substituents can be performed according to the synthesis methods provided in the above embodiments 1 to 3, wherein the spectral data of part of the acetyl glucose thiadiazole benzamide compounds are shown in table 1.
TABLE 1
In addition, the in vitro growth rate method in the prior art is adopted to determine the bacteriostatic activity of the acetylglucose thiadiazole benzamide compound. Specifically, a potato dextrose agar medium (PDA medium: 200g of potato, 20g of agar, 20g of glucose and 1000mL of distilled water) is heated to a molten state (50 ℃), 10mL of a liquid medicine (a liquid medicine containing 10 times of the final concentration of the acetylglucose thiadiazole benzamide compound) is poured into 90mL of the PDA medium, the mixture is fully shaken, and the mixture is uniformly poured into a culture dish with the diameter of 9cm, horizontally placed and cooled and solidified. And (3) punching a bacterium dish with the diameter of 4mm on the edge of the colony of the fresh pathogenic bacterium cultured for 4d by using a puncher, inversely placing the bacterium dish in the center of a PDA (personal digital assistant) plate containing a medicament, then placing the bacterium dish in a constant-temperature constant-humidity incubator at 27 ℃ for inverted culture, observing when a blank control colony grows to a position close to two thirds of the plate, measuring the diameter of the colony by using a cross method, and taking an average value. The blank was dosed with no agent, but contained the same concentration of solvent and 0.5% Tween 20, in triplicate for each treatment. The inhibition rate of the agent on the growth of hyphae is calculated by the following formula:
I(％)＝(C-T)/(C-0.4)×100％；
wherein I is the inhibition, C is the blank control diameter (cm), and T is the treatment diameter (cm). 5 samples were assayed, dose-inhibition curves were plotted, and the EC was calculated50The value is obtained. Each sample was assayed in triplicate and the results expressed as mean ± standard deviation.
Through calculation, the EC of the acetylglucose thiadiazole benzamide compound synthesized in the example 1 on potato late blight pathogenic bacteria506.02. mu.g/mL.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.
Claims (8)
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