CN110878068B - Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone - Google Patents
Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone Download PDFInfo
- Publication number
- CN110878068B CN110878068B CN201911178025.XA CN201911178025A CN110878068B CN 110878068 B CN110878068 B CN 110878068B CN 201911178025 A CN201911178025 A CN 201911178025A CN 110878068 B CN110878068 B CN 110878068B
- Authority
- CN
- China
- Prior art keywords
- dehydroabietic acid
- dichloromethane
- silica gel
- purifying
- separating
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
A synthetic method and application of a fluorescent compound dehydroabietyl-B cyclobenzothiazole-imino- (benzylidene) thiazolinone comprise the following steps: preparing a dehydroabietic acid group B cyclothiazole-amine intermediate by using 6-bromo-7-carbonyl dehydroabietic acid methyl ester prepared by using dehydroabietic acid as a raw material, further reacting with chloroacetyl chloride to obtain dehydroabietic acid group B cyclothiazole-chloroacetamide, reacting with potassium thiocyanate to generate dehydroabietic acid group B cyclothiazole-iminothiazolinone, and finally reacting with benzaldehyde to obtain the dehydroabietic acid group B cyclothiazole-iminothiazolinone. The invention realizes the synthesis of the fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone for the first time. Fluorescence tests and anticancer activity tests show that the compound has certain fluorescence property and anticancer property, and the application range of dehydroabietic acid is expanded. The dehydroabietic acid is a component of natural product rosin, and the preparation method is simple and has low cost.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method and application of a novel rosin derivative based on dehydroabietic acid, thiazole and thiazolidinone, namely dehydroabietic acid-B-cyclothiazothiazole-imino- (benzylidene) thiazolinone.
Background
Thiazole skeleton is widely present in a plurality of natural compounds and active molecules, and often shows a wide range of biological activities such as bacteriostasis, weeding, anti-tumor, antivirus and the like. The thiazolinone backbone also plays an important role in drug design, and its derivatives have also been found to possess a wide range of biological activities such as antibacterial, herbicidal, anticancer, antiviral and anti-inflammatory activities. The fluorescent compounds can be used in drug screening, medical diagnosis, clinical treatment and the like based on molecular recognition. The novel medicinal active compound with the fluorescence function is worthy of further research, so that more effective functional medicaments are developed.
Rosin is an important forest resource in China, is nonvolatile natural resin obtained by processing rosin secreted by pine trees, and mainly comprises diterpene resin acid. The rosin and the deep processing products thereof are applied to the aspects of paper making, printing ink, coating, rubber, adhesive, food additive, biological products and medicinal chemicals. However, the deep processing rate of rosin in China is insufficient, and new methods and new technologies for deep processing of rosin need to be continuously developed, so that the development of the rosin industry is accelerated.
Dehydroabietic acid, also known as dehydroabietic acid or dehydroabietic acid, is a natural component in rosin, and is also a major component of disproportionated rosin, one of the major modified products of rosin, and itself has a wide range of biological activities. The skeleton of dehydroabietic acid molecule contains several reaction centers of carboxyl group, benzene ring, etc. and these positions are used in structure modification to introduce different active groups into dehydroabietic acid molecule to synthesize new dehydroabietic acid-base derivative with excellent bioactivity. The thiazole ring part is introduced into the dehydroabietic acid B ring in a ring-merging mode, so that a conjugated system can be formed by the thiazole ring and the benzene ring of the dehydroabietic acid, the conjugated plane of dehydroabietic acid molecules is enlarged, and a compound with fluorescence property is formed, and the fluorescent compound is worthy of further research.
The dehydroabietic acid-based B-cyclothiazole-imino- (benzylidene) thiazolidinone is a novel fluorescent functional compound, and the substance and the synthetic method thereof are not reported at home and abroad up to now.
Disclosure of Invention
The invention aims to provide a synthesis method of dehydroabietic acid group B cyclo-thiazole-imino- (benzylidene) thiazolidinone, which has simple preparation method and low cost of the obtained product.
The invention adopts the following technical scheme to achieve the aim: dehydroabietic acid based B-cyclothiazole-imino- (benzylidene) thiazolinone, the compound having the formula:
the preparation method of the compound dehydroabietic acid group B cyclothiazole-imino- (benzylidene) thiazolinone comprises the following steps:
(1) Adding 11.0g of methyl 7-carbonyldehydroabietate and 10.0mL of glacial acetic acid into a 50mL three-necked flask, dropwise adding 5.0mL of glacial acetic acid solution containing bromine, wherein the amount of the bromine is 2.3mL, continuing to react for 20min after dropwise addition, adding 3.2g of thiourea, heating to 105 ℃ under stirring, reacting for 12h, distilling under reduced pressure to remove the glacial acetic acid, dissolving the residue with dichloromethane, washing with saturated sodium bicarbonate for 2 times after washing with water for 1 time, drying with anhydrous sodium sulfate, filtering, distilling under reduced pressure to concentrate the reaction solution dissolved by the dichloromethane, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300-mesh silica gel, and eluting with dichloromethane according to the volume ratio: 1, taking a component with a thin-layer chromatography specific transfer value of 0.23-0.34 obtained by spreading a plate with the same proportion of developing agent to obtain dehydroabietic acid group B cyclo-thiazole-amine;
(2) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-amine, 3.5mL of dichloromethane and 200 mu L of triethylamine into a 10mL double-neck flask, dropwise adding 0.07g of chloroacetyl chloride containing 0.5mL of dichloromethane while stirring, reacting at normal temperature for 15min, washing for 1 time after the reaction is ended, washing for 2 times with saturated sodium bicarbonate, drying by anhydrous sodium sulfate, filtering, distilling and concentrating reaction liquid dissolved by dichloromethane under reduced pressure, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: petroleum ether =1, and the dehydroabietic acid based B-cyclothiazole-chloroacetamide is obtained by taking a component with a thin-layer chromatography specific transfer value of 0.44-0.60 obtained by spreading a plate with the same proportion of developing agent;
(3) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-chloroacetamide, 0.5g of potassium thiocyanate, 2mL of absolute ethyl alcohol and 100 mu L of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 3h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, adding 20 mu L of glacial acetic acid, filtering, concentrating the solution dissolved by the dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column chromatography, separating and purifying by using a chromatography column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate according to the volume ratio: petroleum ether =1, and the components with the thin-layer chromatography specific migration value of 0.1-0.2 obtained by spreading a plate with the same proportion of developing agent are taken to obtain dehydroabietic acid group B cyclo-thiazole-imino-thiazolinone;
(4) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-imino-thiazolinone, 0.48g of benzaldehyde, 1mL of absolute ethyl alcohol and 1.5mL of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 8h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, filtering, concentrating the reaction solution dissolved with dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: and (3) petroleum ether =1, and the dehydroabietic acid based B cyclo-thiazole-imino- (benzylidene) thiazolinone is obtained by taking the components with the thin layer chromatography specific transfer value of 0.20-0.24 obtained by spreading a plate by using a spreading agent in the same proportion.
The synthesis method of dehydroabietic acid group B cyclothiazole-imino- (benzylidene) thiazolinone comprises the following reaction:
the preparation method of the intermediate comprises the following steps:
1) Preparation of intermediate dehydroabietic acid group B cyclo-thiazole-amine:
adding 11.0g of 7-carbonyl dehydroabietic acid methyl ester and 10.0mL of glacial acetic acid into a 50mL three-necked bottle, dropwise adding 5.0mL of glacial acetic acid solution containing bromine, wherein the amount of bromine is 2.3mL, continuously reacting for 20min after dropwise adding is finished, then adding 3.2g of thiourea, heating to 105 ℃ under stirring, reacting for 12h, carrying out reduced pressure distillation to remove the glacial acetic acid, dissolving the residue with dichloromethane, washing with water for 1 time, washing with saturated sodium bicarbonate for 2 times, drying with anhydrous sodium sulfate, filtering, concentrating the reaction solution dissolved with dichloromethane through reduced pressure distillation, carrying out chromatographic separation and purification on the concentrated solution with a silica gel column filled with 200-300 meshes of silica gel, and separating and purifying the eluent according to the volume ratio of dichloromethane: 1, taking a component with a thin-layer chromatography specific transfer value of 0.23-0.34 obtained by spreading a plate with the same proportion of developing agent to obtain dehydroabietic acid group B cyclo-thiazole-amine;
2) Preparation of intermediate dehydroabietic acid-based B-cyclothiazole-chloroacetamide:
adding 0.2g of dehydroabietic acid group B cyclo-thiazole-amine, 3.5mL of dichloromethane and 200 mu L of triethylamine into a 10mL double-neck flask, dropwise adding 0.07g of chloroacetyl chloride containing 0.5mL of dichloromethane while stirring, reacting at normal temperature for 15min, washing for 1 time after the reaction is ended, washing for 2 times with saturated sodium bicarbonate, drying by anhydrous sodium sulfate, filtering, distilling and concentrating reaction liquid dissolved by dichloromethane under reduced pressure, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: petroleum ether =1, and the dehydroabietic acid based B-cyclo-thiazole-chloroacetamide is obtained by taking a component with a thin-layer chromatography specific transfer value of 0.44-0.60 obtained by spreading a plate with the same proportion of developing agent;
3) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-chloroacetamide, 0.5g of potassium thiocyanate, 2mL of absolute ethyl alcohol and 100 mu L of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 3h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, adding 20 mu L of glacial acetic acid, filtering, concentrating the solution dissolved by the dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column chromatography, separating and purifying by using a chromatography column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate according to the volume ratio: and (3) petroleum ether = 1.
The invention has the beneficial effects that:
the method takes 6-bromo-7-carbonyl dehydroabietic acid methyl ester prepared by dehydroabietic acid as a raw material to prepare a dehydroabietic acid group B cyclothiazole-amine intermediate, further introduces a thiazolinone skeleton into a molecular structure, and finally obtains the dehydroabietic acid group B cyclothiazole-imino- (benzylidene) thiazolinone. The application of the rosin is expanded, the additional value of the rosin product is improved, and an experimental basis is provided for deep processing of the rosin product.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
Example 1
Preparation of intermediate dehydroabietic acid base B cyclo-thiazole-chloroacetamide:
adding 0.2g of dehydroabietic acid-based B cyclo-thiazole-amine, 3.5mL of dichloromethane and 200 mu L of triethylamine into a 10mL double-neck flask, dropwise adding 0.07g of chloroacetyl chloride (containing 0.5mL of dichloromethane) while stirring, reacting at normal temperature for 15min, washing 1 time after the reaction is finished, washing 2 times with saturated sodium bicarbonate, drying by anhydrous sodium sulfate, filtering, distilling under reduced pressure to concentrate a reaction solution dissolved by dichloromethane, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, wherein the eluent is ethyl acetate: and (3) petroleum ether =1, and the dehydroabietic acid based B-cyclobenzothiazole-chloroacetamide is obtained by taking the components with the thin-layer chromatography specific transfer value of 0.44-0.60 obtained by spreading a plate with the same proportion of developing agent. 1 H NMR(500MHz，CDCl 3 )δ10.06(s，1H，H-NH)，7.69(d，J＝1.9Hz，1H，H-14)，7.23(d，J＝8.0Hz，1H，H-11)，7.18(dd，J＝8.0，1.9Hz，1H，H-12)，4.23(dd，J＝3.0，0.9Hz，2H，H-24)，3.81(s，1H，H-5)，3.72(s，3H，COOCH 3 )，2.97(hept，J＝6.9Hz，1H，H-15)，2.32(dd，J＝17.6，9.0Hz，1H，H 1-e )，1.97–1.78(m，5H，H-3，H-2，H 1-a )，1.65(s，3H，H-19)，1.30(dd，J＝7.0，2.3Hz，6H，H-16，H-17)，1.11(s，3H，H-20). 13 C NMR(126MHz，CDCl 3 )δ178.10，163.51，154.96，147.26，145.13，144.47，129.26，126.96，126.32，122.53，121.42，52.64，46.63，46.24，41.99，39.08，37.74，35.44，33.81，24.08，23.94，21.83，18.14，17.57.Mass spectrum(ESI),m/z：461.1694[M+H] + C 24 H 29 ClN 2 O 3 S caled M 460.1587。
Example 2
Preparation of intermediate dehydroabietic acid group B cyclothiazole-imino-thiazolinone:
adding 0.2g of dehydroabietic acid group B cyclo-thiazole-chloroacetamide, 0.5g of potassium thiocyanate, 2mL of absolute ethyl alcohol and 100 mu L of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 3h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, adding 20 mu L of glacial acetic acid, filtering, concentrating the solution dissolved by the dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column chromatography, separating and purifying by using a chromatography column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate according to the volume ratio: and (3) petroleum ether =1, and the dehydroabietic acid based B-cyclobenzothiazole-imino-thiazolinone is obtained by taking the components with the thin-layer chromatography specific transfer value of 0.1-0.2 obtained by spreading a plate with the same proportion of developing agent. 1 H NMR(500MHz，CDCl 3 )δ12.25–9.36(s，1H，H-N＝C-NH-)，7.81–7.61(m，1H，H-14)，7.26–7.13(m，2H，H-11，H-12)，3.97(t，J＝28.9Hz，1H，H-5)，3.91–3.76(m，2H，H-24)，3.76–3.63(m，3H，COOCH 3 )，2.96(ddd，J＝10.2，9.5，4.6Hz，1H，H-15)，2.32(dd，J＝9.1，5.9Hz，1H，H 1-e )，1.86(dt，J＝41.3，14.2Hz，5H，H-3，H-2，H 1-a )，1.66–1.58(m，3H，H-19)，1.34–1.30(m，6H，H-16，H-17)，1.15–1.09(m，3H，H-20). 13 C NMR(126MHz，CDCl 3 )δ178.30，172.46，166.43，159.05，147.57，147.07，144.31，129.37，129.29，126.26，122.34，122.15，53.43，52.65，46.91，46.56，39.09，37.55，33.79，29.71，23.97，22.70，22.01，18.17，17.39.Mass spectrum(ESI),m/z：484.1724[M+H] + C 25 H 29 N 3 O 3 S 2 caled M 483.1650。
Example 3
Preparation of dehydroabietic acid-based B-cyclothiazole-imino- (benzylidene) thiazolinone:
adding 0.2g of dehydroabietic group B cyclo-thiazole-imino-thiazolinone, 0.48g of benzaldehyde, 1mL of absolute ethyl alcohol and 1.5mL of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 8h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, filtering, concentrating the reaction solution dissolved with dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column chromatography, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, wherein the eluent is ethyl acetate: and (3) petroleum ether = 1. 1 H NMR(500MHz，CDCl 3 )δ12.28–9.68(s，1H，H-N＝C-NH-)，7.93–7.85(m，2H，H-14，H-25)，7.71(d，J＝7.4Hz，1H，H-Ph)，7.70–7.45(m，4H，H-Ph)，7.27–7.19(m，2H，H-11，H-12)，3.87–3.80(m，1H，H-5)，3.69(d，J＝7.7Hz，3H，COOCH 3 )，3.09–3.00(m，1H，H-15)，2.42–2.30(m，1H，H 1-e )，1.96–1.81(m，5H，H-3，H-2，H 1-a )，1.64(d，J＝15.6Hz，3H，H-19)，1.28(dd，J＝21.5，10.3Hz，6H，H-16，H-17)，1.18–1.12(m，3H，H-20). 13 C NMR(126MHz，CDCl 3 ) Delta 178.13, 167.91, 166.87, 166.20, 148.01, 147.42, 146.96, 144.45, 133.73, 130.56, 130.15, 129.82, 129.44, 129.25, 129.15, 126.77, 124.29, 122.38, 121.79, 121.26, 52.62, 47.04, 46.54, 39.17, 37.54, 33.86, 31.52, 29.71, 24.30, 22.10, 18.20, 17.46 fluorescence energy [ methanol solution, ex: lambda ] x max ＝232nm；Em:λ max ＝341nm],Mass spectrum(ESI),m/z：570.1777[M-H] - C 32 H 33 N 3 O 3 S 2 caled M571.1963。
Example 4
The dehydroabietic acid-based B-cyclobenzothiazole-imino- (benzylidene) thiazolinone prepared in the examples 2 to 3 is tested for anticancer activity, and the test method and the result are as follows:
human tongue squamous carcinoma cells cal27, human tongue squamous carcinoma cells scc9, and human kidney epithelial cells 293T, which have been cultured for two days and have good cell morphology, were used as model cells, and after counting the cells by digestion with 0.25% trypsin, the cells were seeded at a density of 5000 cells per well in a 96-well cell culture plate, with a seeding volume per well of 100 μ L. After 24 hours of incubation, 10. Mu.L of different concentrations of drugs were added to the wells to achieve drug concentrations of 100, 50, 25, 12.5,6.25,3.125,1.56, 0. Mu.M (1% DMSO in each well), and the wells were incubated in an incubator for 24 hours. After the incubation time was completed, 10. Mu.L of CCK-8 solution was added to each well of cells, and the cells were incubated in a 37 ℃ cell incubator for 4 hours to measure absorbance at 450nm using a microplate reader. And 5-fluorouracil is selected as a positive control, a hole without the added cell of 0 mu M of the medicine is used as a blank, a hole with the added cell of the 0 mu M of the medicine is used as a negative control, and the inhibition rate is calculated. When the inhibition rate of 100 mu M drug holes does not reach IC 50 Is marked as>100；
Inhibition rate = [ (Ac-As)/(Ac-Ab) ]. Times.100%
As assay well (cell-containing Medium, CCK 8/test substance)
Ac test well (cell-containing Medium, CCK 8/No test substance)
Ab blank well (Medium without cells and test substance, CCK-8)
TABLE 1 anticancer Activity of the target Compounds
* The data in parentheses are the inhibition at 100. Mu.M concentration.
The anticancer activity test shows that the target compound dehydroabietic acid-based B-cyclothiazole-imino- (benzylidene) thiazolinone has certain anticancer activity and IC of human tongue squamous carcinoma cell cal27 and human tongue squamous carcinoma cell scc9 50 32.35 mu M and 5.2 mu M respectively, and has less toxicity to the human kidney epithelial cells 293T of a normal cell model, and the inhibition rate is 13.39 percent under the test concentration of 100 mu M. This result reflects a certain selectivity of the target compound for cancer cells, with the inhibition of cal27 and scc9 by dehydroabietyl B cyclothiazothiazole-imino- (benzylidene) thiazolinone at 100 μ M concentration being 7.18 times and 7.07 times the inhibition of 293T, respectively; compared with commercial positive control 5-fluorouracil, the anticancer activity is better, and the IC of the target compound to cal27 and scc9 50 Are all lower than 5-fluorouracil, and the inhibition rate of the compound on 293T cells at the concentration of 100 mu M is lower than 5-fluorouracil.
Claims (4)
1. Dehydroabietic acid based B-cyclothiazole-imino- (benzylidene) thiazolinone, characterized in that the compound has the following structural formula:
the preparation method of the compound dehydroabietyl acid B cyclothiazole-imino- (benzylidene) thiazolinone comprises the following steps:
(1) Adding 11.0g of 7-carbonyl dehydroabietic acid methyl ester and 10.0mL of glacial acetic acid into a 50mL three-necked bottle, dropwise adding 5.0mL of glacial acetic acid solution containing bromine, wherein the amount of bromine is 2.3mL, continuously reacting for 20min after dropwise adding is finished, then adding 3.2g of thiourea, heating to 105 ℃ under stirring, reacting for 12h, carrying out reduced pressure distillation to remove the glacial acetic acid, dissolving the residue with dichloromethane, washing with water for 1 time, washing with saturated sodium bicarbonate for 2 times, drying with anhydrous sodium sulfate, filtering, concentrating the reaction solution dissolved with dichloromethane through reduced pressure distillation, carrying out chromatographic separation and purification on the concentrated solution with a silica gel column filled with 200-300 meshes of silica gel, and separating and purifying the eluent according to the volume ratio of dichloromethane: 1, taking a component with a thin-layer chromatography specific transfer value of 0.23-0.34 obtained by spreading a plate with the same proportion of developing agent to obtain dehydroabietic acid group B cyclo-thiazole-amine;
(2) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-amine, 3.5mL of dichloromethane and 200 mu L of triethylamine into a 10mL double-neck flask, dropwise adding 0.07g of chloroacetyl chloride containing 0.5mL of dichloromethane while stirring, reacting at normal temperature for 15min, washing for 1 time after the reaction is ended, washing for 2 times with saturated sodium bicarbonate, drying by anhydrous sodium sulfate, filtering, distilling and concentrating reaction liquid dissolved by dichloromethane under reduced pressure, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: petroleum ether =1, and the components with the thin-layer chromatography specific displacement value of 0.44-0.60 obtained by spreading a plate with the same proportion of developing agent are taken to obtain dehydroabietic acid base B cyclo-thiazole-chloroacetamide;
(3) Adding 0.2g of dehydroabietic acid based B cyclo-thiazole-chloroacetamide, 0.5g of potassium thiocyanate, 2mL of absolute ethyl alcohol and 100 mu L of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 3h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, adding 20 mu L of glacial acetic acid, filtering, concentrating the solution dissolved by the dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column chromatography, separating and purifying by using a chromatography column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate according to the volume ratio: petroleum ether =1, and the components with the thin-layer chromatography specific migration value of 0.1-0.2 obtained by spreading a plate with the same proportion of developing agent are taken to obtain dehydroabietic acid group B cyclo-thiazole-imino-thiazolinone;
(4) Adding 0.2g of dehydroabietic acid group B cyclo-thiazole-imino-thiazolinone, 0.48g of benzaldehyde, 1mL of absolute ethyl alcohol and 1.5mL of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 8h, removing the solvent by reduced pressure distillation after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, filtering, concentrating the reaction solution dissolved with dichloromethane by reduced pressure distillation, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: and (3) petroleum ether =1, and the dehydroabietic acid based B cyclo-thiazole-imino- (benzylidene) thiazolinone is obtained by taking the components with the thin layer chromatography specific transfer value of 0.20-0.24 obtained by spreading a plate by using a spreading agent in the same proportion.
2. The method of claim 1, wherein the dehydroabietic acid-based B-cyclothiazole-imino- (benzylidene) thiazolinone is prepared by the following reaction:
3. the method of claim 2, wherein the intermediate is prepared by a method comprising the steps of:
1) Preparation of intermediate dehydroabietic acid group B cyclo-thiazole-amine:
adding 11.0g of methyl 7-carbonyldehydroabietate and 10.0mL of glacial acetic acid into a 50mL three-necked flask, dropwise adding 5.0mL of glacial acetic acid solution containing bromine, wherein the amount of the bromine is 2.3mL, continuing to react for 20min after dropwise addition, adding 3.2g of thiourea, heating to 105 ℃ under stirring, reacting for 12h, distilling under reduced pressure to remove the glacial acetic acid, dissolving the residue with dichloromethane, washing with saturated sodium bicarbonate for 2 times after washing with water for 1 time, drying with anhydrous sodium sulfate, filtering, distilling under reduced pressure to concentrate the reaction solution dissolved by the dichloromethane, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300-mesh silica gel, and eluting with dichloromethane according to the volume ratio: 1, taking a component with a thin-layer chromatography specific transfer value of 0.23-0.34 obtained by spreading a plate with the same proportion of developing agent to obtain dehydroabietic acid group B cyclo-thiazole-amine;
2) Preparation of intermediate dehydroabietic acid-based B-cyclothiazole-chloroacetamide:
adding 0.2g of dehydroabietic acid group B cyclo-thiazole-amine, 3.5mL of dichloromethane and 200 mu L of triethylamine into a 10mL double-neck flask, dropwise adding 0.07g of chloroacetyl chloride containing 0.5mL of dichloromethane while stirring, reacting at normal temperature for 15min, washing for 1 time after the reaction is ended, washing for 2 times with saturated sodium bicarbonate, drying by anhydrous sodium sulfate, filtering, distilling and concentrating reaction liquid dissolved by dichloromethane under reduced pressure, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: petroleum ether =1, and the dehydroabietic acid based B-cyclothiazole-chloroacetamide is obtained by taking a component with a thin-layer chromatography specific transfer value of 0.44-0.60 obtained by spreading a plate with the same proportion of developing agent;
3) Adding 0.2g of dehydroabietic acid-based B cyclo-thiazole-chloroacetamide, 0.5g of potassium thiocyanate, 2mL of absolute ethyl alcohol and 100 mu L of triethylamine into a 10mL double-neck flask, heating to reflux under stirring, reacting for 3h, distilling under reduced pressure to remove the solvent after the reaction is finished, dissolving the residue with dichloromethane, washing for 3 times, drying with anhydrous sodium sulfate, adding 20 mu L of glacial acetic acid, filtering, distilling under reduced pressure to concentrate the dichloromethane-dissolved solution, separating and purifying the concentrated solution by using a silica gel column, separating and purifying by using a chromatographic column filled with 200-300 meshes of silica gel, and eluting with ethyl acetate: and (3) petroleum ether =1, and the dehydroabietic acid based B-cyclobenzothiazole-imino-thiazolinone is obtained by taking the components with the thin-layer chromatography specific transfer value of 0.1-0.2 obtained by spreading a plate with the same proportion of developing agent.
4. Use of dehydroabietic acid based B-cyclothiazothiazole-imino- (benzylidene) thiazolinone according to claim 1 in the preparation of an anticancer agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911178025.XA CN110878068B (en) | 2019-11-27 | 2019-11-27 | Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911178025.XA CN110878068B (en) | 2019-11-27 | 2019-11-27 | Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110878068A CN110878068A (en) | 2020-03-13 |
| CN110878068B true CN110878068B (en) | 2022-11-25 |
Family
ID=69730224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911178025.XA Active CN110878068B (en) | 2019-11-27 | 2019-11-27 | Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110878068B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116283823B (en) * | 2023-03-17 | 2024-04-19 | 广西医科大学 | Synthesis method and application of dehydroabietyl B-cyclobenzothiazole-aniline and diphenylamine compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106045938A (en) * | 2016-06-24 | 2016-10-26 | 广西大学 | Synthesis method of dehydroabietic-acid-based B ring-fused-thiazole-thiocarbamide compounds |
| CN108299330A (en) * | 2018-02-06 | 2018-07-20 | 桂林医学院 | Dehydrogenation Cong Suan oxazolidinone derivatives and its preparation method and application |
-
2019
- 2019-11-27 CN CN201911178025.XA patent/CN110878068B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106045938A (en) * | 2016-06-24 | 2016-10-26 | 广西大学 | Synthesis method of dehydroabietic-acid-based B ring-fused-thiazole-thiocarbamide compounds |
| CN108299330A (en) * | 2018-02-06 | 2018-07-20 | 桂林医学院 | Dehydrogenation Cong Suan oxazolidinone derivatives and its preparation method and application |
Non-Patent Citations (5)
| Title |
|---|
| An efficient synthesis of phenanthro-fused thiazoles by a non-phenolic oxidative coupling procedure of 4,5-diarylthiazoles;I. Moreno等;《Spain SO Tetrahedron Letters》;19990602;第40卷(第27期);5067-5070 * |
| Synthesis and antifungal activity of dehydroabietic acid-based 1,3,4-thiadiazole-thiazolidinone compounds;Naiyuan Chen等;《MOLECULAR DIVERSITY》;20160801;第20卷(第4期);897-905 * |
| Synthesis and antifungal activity of dehydroabietic acid-based thiadiazole phosphonates;Nai-Yuan Chen等;《HOLZFORSCHUNG》;20151130;第69卷(第9期);1069-1075 * |
| 基于去氢枞酸羧基和B环改性的杂环化合物的合成及生物活性研究;陈乃源;《中国博士学位论文全文数据库 工程科技I辑》;20190515;B014-27 * |
| 新型松香基酰基亚胺噻唑烷衍生物的合成;伍勇等;《合成化学》;20121231;第20卷(第5期);606-608 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110878068A (en) | 2020-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111039847B (en) | Magnolol derivative and preparation method and application thereof | |
| CN110878068B (en) | Synthetic method and application of fluorescent compound dehydroabietyl-B cyclothiazole-imino- (benzylidene) thiazolinone | |
| CN106045938B (en) | A kind of synthetic method of dehydrogenation abietyl B rings and thiazole thiourea compound | |
| CN113666824A (en) | Cannabidiol-2-propionate and application thereof | |
| CN113735709A (en) | Cannabidiol-2-butyrate and application thereof | |
| CN110563617A (en) | P-coumaric acid aromatic derivative and preparation method and application thereof | |
| CN110627690A (en) | Novel p-coumaric acid sulfonate derivative and preparation method and application thereof | |
| CN106674128A (en) | Licochalcone A thiouracil derivatives with antitumor activity and synthesis method thereof | |
| CN106632074A (en) | Licochalcone A dihydropyrimidine compound with antitumor activity and synthesizing method thereof | |
| CN110128382A (en) | A kind of preparation method and application of Indian beech seed element | |
| CN101519436A (en) | Cyclic octapeptide compound in Hsisha sponge and application thereof | |
| CN101353333B (en) | 10- deacetylate-9(R)-hydrogenization-1-deoxypaclitaxel analogue and preparation thereof | |
| CN101993359A (en) | Fatty acid derivative of glaucocalyxin A, as well as preparation method and applications thereof | |
| CN110092769A (en) | A kind of chromene derivative and its synthetic method and application | |
| CN102260173A (en) | Ferulic acid derivative of Glaucocalyxin A, its preparation method and its application | |
| CN109503697B (en) | 3- (L-phenylalanine) -pentacyclic triterpene derivative and synthesis method and application thereof | |
| CN116283823B (en) | Synthesis method and application of dehydroabietyl B-cyclobenzothiazole-aniline and diphenylamine compound | |
| CN102276579B (en) | Oligothiophene and preparation method and application thereof | |
| CN102924428B (en) | Oligothiophene | |
| CN114702414B (en) | Phenylacryloyl acid ester derivatives containing n-butyl sulfonate structure and preparation method and application thereof | |
| CN106810563B (en) | Furans card mountain alkane forskolin and its pharmaceutical composition and its application in pharmacy | |
| CN110964033A (en) | Oridonin 14-position hydrogen sulfide donor derivative and preparation method and application thereof | |
| CN1872838A (en) | Compound of monocyclic polysubstitution saturated cyclohexanones, prepartion method and usage | |
| CN101993373A (en) | Chlorinated glaucocalyxin A derivative and preparation method and application thereof | |
| CN109180596B (en) | Anthraquinone triazole nucleoside analogues containing rare glycosyl as well as synthesis method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |