CN110590520A - Synthetic method and application of natural product Xanthohumol D and derivatives thereof - Google Patents

Synthetic method and application of natural product Xanthohumol D and derivatives thereof Download PDF

Info

Publication number
CN110590520A
CN110590520A CN201910919108.3A CN201910919108A CN110590520A CN 110590520 A CN110590520 A CN 110590520A CN 201910919108 A CN201910919108 A CN 201910919108A CN 110590520 A CN110590520 A CN 110590520A
Authority
CN
China
Prior art keywords
mmol
product
xanthohumol
natural product
column chromatography
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201910919108.3A
Other languages
Chinese (zh)
Inventor
陈志伟
桑锋
孔玲
付林
李媛媛
刘雪
刘士霖
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong University of Technology
Original Assignee
Shandong University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shandong University of Technology filed Critical Shandong University of Technology
Priority to CN201910919108.3A priority Critical patent/CN110590520A/en
Publication of CN110590520A publication Critical patent/CN110590520A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a synthetic method and application of a natural product Xanthohumol D (I) and an analogue (II) thereof, wherein the structural formula of the natural product Xanthohumol D (I) is as follows: the obtained novel prenylchalcone compounds have good inhibition activity of Xanthohumol D on bacillus subtilis. The preparation route of the invention has fewer process steps and easily obtained raw materials, and is suitable for industrial production.

Description

Synthetic method and application of natural product Xanthohumol D and derivatives thereof
Technical Field
The invention relates to the field of compound synthesis, in particular to a synthesis method of a natural product Xanthohumol D and an analogue thereof.
Background
(E) -1- (2, 4-dihydroxy-3- (2-hydroxy-3-methylbutyl-3-en-1-yl) -6-methoxyphenyl) -3- (4-hydroxyphenyl) prop-2-en-1-one Xanthohumol D and analogs thereofHumulus lupulusThe chemical preparation method and the structure-activity relationship research of the compound are not reported so far, and the chemical preparation and the structure modification research of the compound have more important scientific significance.
Disclosure of Invention
The invention aims to provide a synthetic method and application of a natural product Xanthohumol D and analogues thereof.
The invention also aims to provide the application of the two natural products in inhibiting escherichia coli, pseudomonas aeruginosa, staphylococcus aureus and bacillus subtilis.
The natural product Xanthohumol D (I) and the analogue (II) thereof have the following structural formula:
the synthetic route of the natural product Xanthohumol D is as follows:
。
the preparation method of the natural product Xanthohumol D comprises the following steps:
(1) dissolving 2,4, 6-trihydroxyacetophenone, potassium carbonate and chloromethyl methyl ether in acetone 60oC, reacting, extracting, drying and carrying out column chromatography to obtain a product 2;
(2) 65 reaction of the product 2 obtained in step (1), potassium carbonate and 1-bromo-3-methyl-2-butene in acetoneoC lower part of the bodyPerforming flow reaction, extracting, drying and performing column chromatography to obtain a product 4;
(3) 200 reaction of the product 4 obtained in the step (2) in N, N-dimethylanilineoC, carrying out reflux reaction, carrying out reduced pressure concentration and column chromatography to obtain a product 5;
(4) carrying out 150 reaction on the product 5 obtained in the step (3), potassium carbonate and methyl iodide in N, N-dimethylformamideoC, carrying out reflux reaction, extracting, drying and carrying out column chromatography to obtain a product 6;
(5) reacting the product 6 obtained in the step (4), the raw material 7 and 5M sodium hydroxide in ethanol at room temperature, and extracting, drying and carrying out column chromatography to obtain a product 8;
(6) adding the target product 8 obtained in the step (5) and tetraphenylporphyrin into dichloromethane, illuminating with a 500W halogen lamp until the raw materials react completely, adding triphenylphosphine, stirring overnight at room temperature, and performing reduced pressure concentration and column chromatography to obtain a target product 9;
(7) and (3) adding the product 9 obtained in the step (6) and p-toluenesulfonic acid into methanol and tetrahydrofuran for reflux reaction, and extracting, drying and carrying out column chromatography to obtain the target product (I).
Wherein:
in the step (1), the dosage ratio of the 2, 4-dihydroxy acetophenone, the potassium carbonate, the chloromethyl methyl ether and the acetone is 1 mmol: 7 mmol: 2.5 mmol: 3 mL.
In the step (1), the oil bath is controlled at a temperature of 60 DEGoC, reaction time is 5 h.
In the step (2), the ratio of the product 2 obtained in the step (1) to the potassium carbonate, 1-bromo-3-methyl-2-butene and acetone is 1 mmol: 4 mmol: 1.5 mmol: 8 mL.
In the step (2), the room temperature is 65 DEGoC, the reaction time is 4 h.
In the step (3), the ratio of the product 4 in the step (2) to the N, N-dimethylaniline is 1 mmol: 10 mL.
In the step (3), the temperature is controlled to 185oC～200 oAnd C, reacting for 2-3 h.
In the step (4), the ratio of the amount of the product 5 in the step (3) to the amount of potassium carbonate, methyl iodide and N, N-dimethylformamide is 1 mmol: 5 mmol: 2.5 mmol: 8 mL.
In the step (4), the room temperature is 150 DEGoAnd C, reacting for 1 h.
In the step (5), the dosage ratio of the product 6 in the step (4) to aldehyde, 5M sodium hydroxide and ethanol is 1 mmol: 1.2 mmol: 40 mmol: 7.5 mL.
In the step (5), the temperature is 25-35 DEGoAnd C, the reaction time is 24 ~ 30 h.
In the step (6), the using amount ratio of the product 8 in the step (5) to tetraphenylporphyrin, triphenylphosphine and dichloromethane is 1 mmol: 0.1 mmol: 1.1 mmol: 100 mL.
In the step (6), the reaction temperature is controlled to be 5-10 ℃ under illuminationoC, the reaction time is 6-8 h
In the step (6), triphenylphosphine is added, and the reaction temperature is 20-30 DEGoAnd C, reacting for 10-15 h.
In the step (7), the using amount ratio of the product 9 in the step (6) to the p-toluenesulfonic acid, the methanol and the tetrahydrofuran is 1 mmol: 1 mmol: 10 mL: 10 mL.
In the step (7), the reflux temperature is 50-55 DEGoAnd C, the reaction time is 15-20 h.
The synthetic route of the analogue (II) is as follows:
the preparation method of the natural product comprises the following steps:
(1) refluxing 2,4, 6-trihydroxyacetophenone, potassium carbonate and dimethyl sulfate in acetone in an oil bath, extracting, drying and carrying out column chromatography to obtain a product 10;
(2) reacting the product 10 obtained in the step (1), diisopropylethylamine and 1-bromo-3-methyl-2-butene in dichloromethane at room temperature, and extracting, drying and carrying out column chromatography to obtain a product 11;
(3) reacting the product 11 obtained in the step (2), diisopropylethylamine and chloromethyl methyl ether in dichloromethane at room temperature, and obtaining a product 12' through extraction, drying and column chromatography;
(4) reacting the product 12 obtained in the step (3), the raw material 13 and 5M sodium hydroxide in ethanol at room temperature, and extracting, drying and carrying out column chromatography to obtain a product 14;
(5) adding the target product 14 obtained in the step (4) and tetraphenylporphyrin into dichloromethane, illuminating with a 500W halogen lamp until the raw materials react completely, adding triphenylphosphine, stirring overnight at room temperature, and performing reduced pressure concentration and column chromatography to obtain a target product 15;
(6) and (3) adding the product 15 obtained in the step (5) and p-toluenesulfonic acid into methanol and tetrahydrofuran for reflux reaction, and extracting, drying and carrying out column chromatography to obtain a target product (II).
Wherein:
in the step (1), the dosage ratio of the 2,4, 6-trihydroxyacetophenone, the potassium carbonate, the dimethyl sulfate and the acetone is 1 mmol: 3 mmol: 0.6 mmol: 3 mL.
In step (1), the oil bath is controlled at a temperature of 65 DEGoC, reaction time is 24 h.
In the step (2), the ratio of the product 10 obtained in the step (1) to diisopropylethylamine, 1-bromo-3-methyl-2-butene and dichloromethane is 1 mmol: 4 mmol: 1.5 mmol: 5 mL.
In the step (2), the room temperature is 25 DEGoC, the reaction time is 4 h.
In the step (3), the ratio of the product 11 in the step (2) to the amounts of diisopropylethylamine, chloromethyl methyl ether and dichloromethane is 1 mmol: 5 mmol: 2.5 mmol: 10 mL.
In the step (3), the temperature is controlled to 25 DEGoC～30 oC, reaction time is 24 h.
In the step (4), the ratio of the product 12 in the step (3) to the raw material 13 and 5M sodium hydroxide in ethanol is 1 mmol: 1.3 mmol: 30 mmol: 7.5 mL.
In the step (4), the room temperature is 30 DEGoAnd C, the reaction time is 10 h.
In the step (5), the ratio of the product 14 in the step (4) to the amounts of tetraphenylporphyrin, triphenylphosphine and dichloromethane is 1 mmol: 0.1 mmol: 1.1 mmol: 100 mL.
In the step (5), the reaction temperature is controlled to be 5-10 ℃ under illuminationoC, the reaction time is 6-8 h
In the step (5), triphenylphosphine is added, and the reaction temperature is 20-30 DEGoAnd C, reacting for 10-15 h.
In the step (6), the using amount ratio of the product 15 in the step (5) to the p-toluenesulfonic acid, the methanol and the tetrahydrofuran is 1 mmol: 1 mmol: 10 mL: 10 mL.
In the step (6), the reflux temperature is 50-55 DEGoAnd C, the reaction time is 15-20 h.
The natural product Xanthohumol D and the analogue thereof are used for preparing antibacterial drugs.
The invention has the following beneficial effects:
the preparation route of the invention has fewer process steps and easily obtained raw materials, and is suitable for industrial production. The natural product Xanthohumol D and the analogue thereof are obtained, and have certain inhibitory activity on the growth of the bacillus subtilis.
Detailed Description
In order that the objects and advantages of the invention will be more clearly understood, the invention is further described in detail below with reference to examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention
The embodiment of the invention provides a synthetic method of a natural product Xanthohumol D (I) and an analogue (II) thereof, and the synthetic route is as follows:
(1) mixing 2,4, 6-trihydroxyacetophenone (1 mmol) and potassium carbonate (5 mmol)、Placing in round bottom flask, adding 3 mL acetone as reaction solvent, adding chloromethyl methyl ether (2.5 mmol) at room temperature, stirring for 20 min while maintaining temperature, transferring to oil bath 60oC refluxing for 5 hours and reactingAnd (4) completing. Extracting and separating liquid by using water and ethyl acetate, reserving an organic layer, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure, and carrying out column chromatography to obtain a product 2;
(2) placing the product 2 (1 mmol) obtained in the step (1) and potassium carbonate (4 mmol) in a round-bottom flask, adding acetone (8 mL) as a reaction solvent, adding 1-bromo-3-methyl-2-butene (1.5 mmol) at room temperature, stirring for 4 hours to complete the reaction, extracting with water and ethyl acetate, retaining an organic layer, drying over anhydrous sodium sulfate, concentrating under reduced pressure, and carrying out column chromatography to obtain a product 4;
(3) putting the product 4 (1 mmol) obtained in the step (2) and N, N-dimethylaniline into a round-bottom flask, and controlling the temperature to be 185oC~200oC, maintaining the temperature, stirring for 1.5 h, and performing column chromatography to obtain a product 5;
(4) placing the product 5 (1 mmol) obtained in the step (3), potassium carbonate (5 mmol) and N, N-dimethylformamide (8 mL) in a round-bottom flask, adding methyl iodide (2.5 mmol) at room temperature, and controlling the temperature to be 150 DEGoC, maintaining the reaction for 1 hour, completely reacting, and obtaining a product 6 through extraction, drying and column chromatography;
(5) placing the product 6 (1 mmol) obtained in the step (4) and the raw material 6 (1.2 mmol) in a round-bottom flask, adding ethanol (7.5 mL) as a reaction solvent, adding 5M NaOH (7.5 mL) at room temperature, continuing stirring for 30 h, extracting and separating by using water and ethyl acetate, reserving an organic layer, drying by using anhydrous sodium sulfate, and carrying out column chromatography by concentration under reduced pressure to obtain a product 8;
(6) placing the product 8 (1 mmol) obtained in the step (5) and tetraphenylporphyrin (0.1 mmol) in a round-bottom flask, adding dichloromethane (100 mL) as a reaction solvent, cooling in an ice-water bath, irradiating and stirring under a 500w halogen lamp for 6 hours, adding triphenylphosphine (1.1 mmol), naturally raising the temperature to room temperature, continuing stirring overnight, concentrating under reduced pressure, and carrying out column chromatography to obtain a target product 9;
(7) dissolving the product 9 (1 mmol) obtained in the step (6) with methanol (10 mL) and tetrahydrofuran (10 mL), adding p-toluenesulfonic acid (1 mmol), and heating in oil bath to 50 DEGoC, reacting for 15 hours, and then adding water and acetic acid BExtracting with ester, separating, keeping organic layer, drying, concentrating under reduced pressure, and performing column chromatography to obtain natural product (I).
The invention provides another synthetic method of natural products, and the synthetic route is as follows:
(1) mixing 2,4, 6-trihydroxyacetophenone (1 mmol) and potassium carbonate (3 mmol)、Placing in round bottom flask, adding 3 mL acetone as reaction solvent, adding dimethyl sulfate (0.6 mmol) at room temperature, stirring for 20 min, transferring to oil bath 65oThe reaction was complete after 24 hours of C reflux. Extracting and separating liquid by using water and ethyl acetate, reserving an organic layer, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure, and carrying out column chromatography to obtain a product 10;
(2) placing the product 10 (1 mmol) obtained in the step (1) and diisopropylethylamine (4 mmol) in a round-bottom flask, adding 5mL of dichloromethane as a reaction solvent, adding 1-bromo-3-methyl-2-butene (1.5 mmol) at room temperature, stirring for 4h at room temperature, extracting with water and ethyl acetate, drying the organic phase with anhydrous magnesium sulfate, and performing column chromatography to obtain a product 11;
(3) placing the product 11 (1 mmol) obtained in the step (2) and diisopropylethylamine (5 mmol) in a round-bottom flask, using 10mL dichloromethane as a solvent, slowly adding chloromethyl methyl ether (2.5 mmol) under stirring at room temperature, stirring for 24h while maintaining the temperature, extracting with water and ethyl acetate, collecting an organic phase, drying with anhydrous magnesium sulfate, and carrying out column chromatography to obtain a product 12;
(4) and (3) placing the product 12 (1 mmol) obtained in the step (3) and the raw material 13 (1.3 mmol) in a round-bottom flask, adding 7.5mL of absolute ethyl alcohol, magnetically stirring in an ice bath, preparing 7.5mL of 5M sodium hydroxide solution, slowly adding the mixture into the reaction system, maintaining the stirring in the ice bath for 20 minutes, and removing the ice bath to react at room temperature for 10 hours. Extracting with water and ethyl acetate, collecting organic phase, drying with anhydrous magnesium sulfate, and performing column chromatography to obtain product 14;
(5) dissolving the target product 14 (1 mmol) obtained in the step (4) in a round-bottom flask by using 100mL of dichloromethane, magnetically stirring in an ice bath, adding tetraphenylporphyrin (0.1 mmol), illuminating by using a 500W halogen lamp, maintaining the temperature at 5 ℃ of ~ 10 ℃, completely reacting the raw materials, adding triphenylphosphine (1.1 mmol), stirring at room temperature overnight, concentrating under reduced pressure, and carrying out column chromatography to obtain a target product 15;
(6) placing the product 15 (1 mmol) obtained in the step (5) and p-toluenesulfonic acid (1 mmol) in a round-bottom flask, using methanol (10 mL) and tetrahydrofuran (10 mL) as reaction solvents, and placing the flask in an oil bath at 50 ℃ for reflux reaction. Extracting with water and ethyl acetate, collecting organic phase, drying with anhydrous magnesium sulfate, and performing column chromatography to obtain target product (II).
The test results of the natural product Xanthohumol D and the analogue products thereof are as follows:
(E) -1- (2, 4-dihydroxy-3- (2-hydroxy-3-methylbutyl-3-en-1-yl) -6-methoxyphenyl) -3- (4-hydroxyphenyl) prop-2-en-1-one
Yellow solid, yield 17% (total yield of 6 steps),1H NMR (400 MHz, Acetone-d 6) δ 14.99 (s, 1H), 10.04 (s, 1H), 8.96 (s, 1H), 7.91 (d,J = 15.5 Hz, 1H), 7.76 (d, J = 15.5 Hz, 1H), 7.63 (s, 1H), 7.61 (s, 1H), 6.93 (s, 1H), 6.91 (s, 1H), 6.08(s, 1H), 5.51 (s, 1H), 4.96 (s, 1H), 4.77 (s, 1H), 4.39 – 4.31 (m, 1H), 3.96(s, 3H), 3.04 (dd,J = 14.6, 2.9 Hz, 1H), 2.82 (dd, J = 14.6, 8.1 Hz, 1H), 1.82 (s, 3H).
13C NMR (101 MHz, Acetone-d 6) δ 193.32, 166.73, 165.05, 162.58, 160.67, 148.34, 143.34, 131.31, 128.12, 125.39, 116.84, 110.28, 106.68, 106.10,92.73, 77.01, 56.24, 20.70, 18.50.
(E) -1- (2, 6-dihydroxy-3- (2-hydroxy-3-methylbutyl-3-en-1-yl) -4-methoxyphenyl) -3-phenylprop-2-en-1-one
Yellow solid, yield 18% (total yield of 6 steps),1H NMR (400 MHz, Acetone-d6) δ 12.84 (brs, 1H), 11.65 (brs, 1H), 8.30 (d, J = 15.6 Hz, 1H), 7.79 (d, J = 15.7 Hz,1H), 7.75 – 7.67 (m, 2H), 7.49 – 7.40 (m, 3H), 6.13 (s, 1H), 5.40 (brs, 1H),4.93 (s, 1H), 4.77 (s, 1H), 4.31 (dd, J = 8.3, 3.0 Hz, 1H), 3.86 (s, 3H),3.00 (dd, J = 14.4, 3.2 Hz, 1H), 2.93 (s, 1H), 2.76 (dd, J = 14.4, 8.3 Hz,1H), 1.81 (d, J = 8.6 Hz, 3H).
13C NMR (101 MHz, Acetone-d6) δ 193.59, 165.11, 164.84, 161.75, 148.00, 142.40, 136.19, 130.64, 129.52, 128.88, 128.36, 110.05, 106.60, 106.54,92.15, 77.02, 55.93, 29.61, 17.94
the following antibacterial experimental studies were carried out on the natural product Xanthohumol D and its analogues:
1. experimental Material
1.1 bacterial species
Bacillus subtilisBacillus subtilis (B. subtilis)[CMCC(B)63 501],
Staphylococcus aureusStaphylococcus aureus (S. aureus) [CMCC(B)260003],
Escherichia coliEscherichia coli (E. coli) [CMCC(B)44102] ,
Pseudomonas aeruginosaPseudomonas aeruginosa (P. aeruginosa) [CMCC(B)10104]
1.2 reagents
LB (Luria Bertani) solid medium, LB liquid medium, drug mother liquor. The others are domestic pure chemical reagents.
2. Experimental methods
2.1 preparation of the culture Medium
Lb (luria bertani) solid medium: 10 g of peptone, 5 g of yeast extract powder and 10 g of sodium chloride (NaCl), wherein the volume is fixed to 1L by using distilled water, and agar powder is added according to the proportion of 1.0-1.5%. Adjusting the pH value to about 7.4 by 1 mol/L NaOH, and sterilizing for 20 min at 121 ℃ by high-pressure steam for later use.
2.2 preparation of mother liquor of Natural product Xanthohumol D and its analogues
Accurately weighing 50mg of the sample to be detected respectively, adding into a sterilized 1.5mL centrifuge tube, adding 1mL DMSO to prepare 50mg/mL mother solution, and-40oAnd C, freezing and storing. Before use, the culture medium is added to be diluted to corresponding concentration for application after being thawed.
2.3 rejuvenation and purification of the Strain
(1) Taking out the glycerol tube containing the strain to be tested from a refrigerator at the temperature of-80 ℃;
(2) inoculating and culturing: after the bacterial liquid in the glycerin pipe is melted, sucking 200 uL of liquid in the superclean workbench by using a liquid-transferring gun
Putting the mixture into a sterilized PA bottle filled with 5mL of LB culture medium, and culturing for 12 h at 37 ℃ by a shaking table at 200 rpm;
(3) and (4) purity testing: dipping the cultured bacteria liquid on the poured LB solid plate by an inoculating loop in an ultra-clean workbench
Streaking, and culturing in a constant-temperature incubator at 37 ℃ for 12 h for purity test.
(4) Inoculation: picking a single colony from the purified plate in a clean bench to inoculate the colony containing 5mL of LB
Culturing in a liquid culture medium PA bottle at 37 deg.C with shaking table at 200 rpm for 12 h, storing at 4 deg.C as the bacterial liquid to be tested,
the product can be used within three days;
2.4 agar dilution method
Adding antibacterial drugs with different dosages into quantitative LB agar which is melted and cooled to about 50 ℃ to prepare flat plates containing the antibacterial drugs with different degressive concentrations, inoculating tested bacteria, and observing the growth condition of the bacteria after incubation so as to ensure that the minimum drug concentration contained in the agar plate for inhibiting the growth of the bacteria is MIC. The method has the advantages that the method can simultaneously measure the Minimum Inhibitory Concentration (MIC) of a plurality of strains on one flat plate, has reliable result and is easy to find the pollution bacteria.
(1) Preparing a drug-containing flat plate: respectively taking natural product Xanthohumol D and analogue mother liquor 50 thereofμL，25μL，12.5μL, adding into 50 mL LB medium, pouring into a flat plate in an ultraclean bench to obtain a product with a thickness of 3 ~ 4 mm, and making into a product with a drug-containing concentration of 50μg/mL，25μg/mL，12.5μg/mL of the drug-containing plate.
(2) Culturing four test bacteria (escherichia coli, staphylococcus aureus, pseudomonas aeruginosa and bacillus subtilis) and preparing gradient diluents: the four bacteria were inoculated into a PA flask containing 5mL of LB medium and cultured at 37 ℃ for 12 hours with a shaker at 200 rpm. Diluting the cultured bacterial liquid to 10% with normal saline-1，10-2，10-3，10-4，10-5，10-6Six gradients of bacterial liquid.
(3) Sample application: in a clean bench, 1.5 percent of diluted bacteria liquid is suckedμL are dropped on the drug-containing flat plate in sequence,
there are 24 spots in a plate.
(4) Culturing: placing the plate with the spotted sample in a constant temperature incubator at 37 ℃ for culture, and observing bacterial colonies after the culture is finished
And (4) growing.
And (3) bacteriostasis result:
the compound Xanthohumol D only carries out bacteriostasis test on the bacillus subtilis, and the concentration of the compound is 25μHas inhibitory activity to the bacterium at g/mL; the analogue (II) has bacteriostasis tests on four bacteria, and has no inhibitory activity.

Claims (4)

1. A natural product Xanthohumol D (I) and an analogue (II) thereof are synthesized and used, and the structural formula is as follows:
。
2. the method for synthesizing the natural product Xanthohumol D and the use thereof as claimed in claim 1, wherein the synthetic route is as follows:
。
3. the synthesis method and the application of the analogue (II) as described in the patent claim 1, wherein the synthesis route is as follows:
。
4. the natural product Xanthohumol D and the analogue thereof are used for preparing antibacterial drugs.
CN201910919108.3A 2019-09-26 2019-09-26 Synthetic method and application of natural product Xanthohumol D and derivatives thereof Withdrawn CN110590520A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910919108.3A CN110590520A (en) 2019-09-26 2019-09-26 Synthetic method and application of natural product Xanthohumol D and derivatives thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910919108.3A CN110590520A (en) 2019-09-26 2019-09-26 Synthetic method and application of natural product Xanthohumol D and derivatives thereof

Publications (1)

Publication Number Publication Date
CN110590520A true CN110590520A (en) 2019-12-20

Family

ID=68864003

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910919108.3A Withdrawn CN110590520A (en) 2019-09-26 2019-09-26 Synthetic method and application of natural product Xanthohumol D and derivatives thereof

Country Status (1)

Country Link
CN (1) CN110590520A (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109053406A (en) * 2018-08-30 2018-12-21 中国农业科学院农产品加工研究所 Chalcone compound and its preparation method and application derived from alpha, beta-lonone

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109053406A (en) * 2018-08-30 2018-12-21 中国农业科学院农产品加工研究所 Chalcone compound and its preparation method and application derived from alpha, beta-lonone

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
KAZUHIRO SUGAMOTO等: "Synthesis and antibacterial activity of chalcones bearing prenyl or geranyl groups from Angelica keiskei", 《TETRAHEDRON》 *
VICTOR KUETE等: "Antimicrobial activity of the methanolic extract, fractions and four flavonoids from the twigs ofDorstenia angusticornis Engl. (Moraceae)", 《JOURNAL OF ETHNOPHARMACOLOGY》 *
XIAOWU DONG等: "Synthesis of Four Natural Prenylflavonoids and Their Estrogen-like Activities", 《ARCH. PHARM. CHEM. LIFE SCI.》 *
YUANYUAN LI等: "Synthesis and antibacterial activity of four natural chalcones and their derivatives", 《TETRAHEDRON LETTERS》 *
付林等: "5′位羟基异戊烯基查尔酮类天然产物的合成及其抗菌活性研究", 《有机化学》 *

Similar Documents

Publication Publication Date Title
WO2023070996A1 (en) Diphenyl ether ester compound and application thereof, and pesticide bactericide
CN104860909B (en) The antibacterial activity application of griseofulvin derivative, griseofulvin and its derivative
CN112111410B (en) Preparation method of dibenzooxepinone compound
CN110590520A (en) Synthetic method and application of natural product Xanthohumol D and derivatives thereof
CN106085415B (en) A kind of jamaicin affinity labeling probe and preparation method thereof
CN109705101B (en) Pyrazole triazole sulfonamide compound and solvothermal synthesis method and application thereof
CN107522702A (en) A kind of new indole class compound and preparation method thereof
CN110590530A (en) Synthesis method and application of natural product Bartericin A and derivatives thereof
JPH0115491B2 (en)
CN110590521A (en) Synthesis method and application of natural products Stipulin and Angusticornin B
CN112480031B (en) Emodin amide derivatives containing 1,3, 4-thiadiazole, and synthesis method and application thereof
CN112409157A (en) Preparation method and application of plant extract and derivatives thereof
CN111647004B (en) Propenone derivative for removing N-methylofloxacin and preparation method and application thereof
CN109206395A (en) The synthetic method and its agricultural biological activity of benzo oxa- class compound
CN109503612B (en) Structure modifier of 8-methoxypsoralen and preparation method and application thereof
CN110452106A (en) The synthetic method and purposes of a kind of natural products Xanthoangelol D and its derivative
CN110483266A (en) The synthetic method and purposes of a kind of natural products Kanzonol C and its derivative
CN108558905B (en) Thiopyran [4,3-b ] indole compound and preparation method and application thereof
CN110437194A (en) A kind of synthetic method and purposes of natural products Angusticornin A
CN113149927B (en) Vanillin isoxazole compound and preparation method and application thereof
CN111269247A (en) Preparation method of buprofezin drug molecule with escherichia coli inhibition effect
CN110437049A (en) A kind of synthetic method and purposes of natural products Paratocarpin E
CN114940665B (en) Benzisothiazolinone compound serving as bactericide and preparation method thereof
CN114478467B (en) Fluoro-cyclohexanone spiro 1, 3-dioxane chiral derivative and preparation method thereof
CN114292193B (en) Depsipeptide cyclic ether compound, bacterial strain, preparation method and application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication
WW01 Invention patent application withdrawn after publication

Application publication date: 20191220