CN111039998A - Preparation method of 8-benzenesulfonyl substituted flavone glucose glycoside - Google Patents
Preparation method of 8-benzenesulfonyl substituted flavone glucose glycoside Download PDFInfo
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Abstract
本发明涉及一种8‑苯磺酰基取代的黄酮葡萄糖糖苷及其制备方法，属于有机化学技术领域。一种8‑苯磺酰基取代的黄酮葡萄糖糖苷，具有以下结构：其中，R1包括未取代的C6‑10芳基，卤素、烷基或烷氧基取代的芳基；R2包括烷氧基取代的芳基。本发明使用的原料价格低廉，绿色环保，操作简单，且合成的衍生物具有抑制肿瘤细胞生物活性。The invention relates to an 8-benzenesulfonyl-substituted flavonoid glucoside and a preparation method thereof, belonging to the technical field of organic chemistry. An 8-benzenesulfonyl-substituted flavonoid glucoside having the following structure: Wherein, R 1 includes unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; R 2 includes alkoxy substituted aryl. The raw materials used in the invention are low in price, green and environmentally friendly, and simple in operation, and the synthesized derivatives have the biological activity of inhibiting tumor cells.
Description
Technical Field
The invention relates to 8-benzenesulfonyl substituted flavone glucose glycoside and a preparation method thereof, belonging to the technical field of organic chemistry.
Background
The 8-benzenesulfonyl substituted flavone glucoside is a core skeleton structure of bioactive substances, synthetic drugs and natural drugs, and has wide application in biological and pharmacological research. In addition, the glycoside derivative part of the 8-benzenesulfonyl substituted flavone has the functions of resisting bacteria, inflammation and malaria. The glycoside derivatives of 8-phenylsulfonyl-substituted flavones as key intermediates for the synthesis of some important compounds necessitate further investigation.
Disclosure of Invention
In view of the above problems, the present invention provides an 8-benzenesulfonyl substituted flavone glucoside, having the structure shown in formula III below:
wherein R is1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; (ii) a R2Including alkoxy substituted aryl groups.
In one embodiment of the present invention, the substrate is,
the R is1Comprises that
The R is2Comprises that
The second purpose of the invention is to provide a preparation method of 8-benzenesulfonyl substituted flavone glucose glycoside, which comprises the following steps: dissolving the 8-benzenesulfonyl substituted flavonol and alkali in an organic solvent in an inert gas atmosphere, and adding a glucose derivative for reaction to obtain the 8-benzenesulfonyl substituted flavone glucose glycoside derivative; and (3) hydrolyzing the 8-benzenesulfonyl substituted flavone glucoside derivative under alkaline conditions to obtain the 8-benzenesulfonyl substituted flavone glucoside.
In one embodiment, the 8-benzenesulfonyl substituted flavonol has the structure shown in formula I
Wherein R is1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; (ii) a R2Including alkoxy substituted aryl groups.
In one embodiment, R in the structure of the 8-benzenesulfonyl-substituted flavonol1Comprises that
R in the structure of the 8-benzenesulfonyl substituted flavonol2Comprises that
In one embodiment, a method for preparing an 8-benzenesulfonyl substituted flavonol comprises: dissolving flavonoid shown in formula II in a mixed organic solvent, and carrying out a first-step reaction under the action of a buffer solution and an oxidant; in the formula II R1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; r2Including alkoxy-substituted aryl groups;
and after the first step of reaction is finished, adding organic acid to carry out a second step of reaction to obtain the 8-benzenesulfonyl substituted flavonol.
In one embodiment, the buffer comprises a solution of an inorganic base, preferably NaHCO3And Na2CO3An aqueous solution of (a);
the oxidant comprises an inorganic oxidant, preferably potassium hydrogen peroxymonosulfate composite salt water solution;
the mixed organic solvent comprises a mixture of dichloromethane and acetone, a mixture of toluene and acetone, a mixture of tetrahydrofuran and acetone, a mixture of acetonitrile and acetone, a mixture of dichloroethane and acetone, a mixture of carbon tetrachloride and acetone, a mixture of chloroform and acetone, and a mixture of hexafluoroisopropanol and acetone;
the organic acid comprises p-toluenesulfonic acid and caprylic acid;
the reaction temperature of the first step and the reaction temperature of the second step are both 15-35 ℃, and the reaction time of the first step and the reaction time of the second step are 40-50 hours.
In one embodiment, the mass ratio of flavonoids of formula II to oxidizing agent is 1:5 to 25; the adding amount of the organic solvent is 30-40 mL/mmol based on the amount of the flavonoid substance shown in the formula II.
In one embodiment, the base is an inorganic base, preferably the base comprises potassium carbonate, potassium acetate, potassium phosphate, sodium carbonate;
the glucose derivative comprises halogenated acetyl glucose, preferably the glucose derivative comprises bromoacetyl glucose and chloroacetyl glucose;
the organic solvent comprises dichloromethane, toluene, tetrahydrofuran, acetonitrile, dichloroethane and acetone.
In one embodiment, the reaction temperature is 15-35 ℃, and the reaction time is 12-14 h; the mass ratio of the 8-benzenesulfonyl substituted flavonol to the alkali to the glucose derivative is 1: 5.4-6.0: 2.4-3.0; the amount of the organic solvent added is 80-100 mL/mmol based on the amount of the 8-benzenesulfonyl-substituted flavonol.
In one embodiment, the purification method of the 8-benzenesulfonyl substituted flavone glucoside comprises the following steps: adding column chromatography silica gel into the obtained reaction liquid, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the crude product, eluting with mixed liquid of petroleum ether and ethyl acetate, carrying out TLC elution tracking detection, collecting eluent containing a target product, merging the target product eluent, and evaporating and concentrating to obtain the 8-benzenesulfonyl substituted flavone glucose glycoside.
Has the advantages that:
the invention provides 8-benzenesulfonyl substituted flavone glucose glycoside, which is a core skeleton structure of bioactive substances, synthetic drugs and natural drugs and has wide application in the research of physics and pharmacology. In addition, the 8-benzenesulfonyl substituted flavone glucoside derivative has the functions of resisting bacteria, inflammation and malaria, and the 8-benzenesulfonyl substituted flavone glucose glucoside is a key intermediate for synthesizing some important compounds.
The invention also provides a simple method for synthesizing the 8-benzenesulfonyl substituted flavone glucose glycoside, the method has the advantages of less raw material consumption, simple operation, mild condition and better yield, and the glycoside derivative of the sulfur-containing flavonol can be synthesized with high selectivity according to reactants, reaction time and temperature.
Drawings
FIG. 1 is a single crystal structural diagram of 8-benzenesulfonyl substituted flavonol prepared in example 1.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the following specific examples.
The starting flavonoids used in the present invention may be prepared on their own according to the existing literature, for example literature Zou, l.h.; zhao, c.; li, p.g.; wang, y.; li, J.J.org.chem.2017,82, 12892-12898.
Example 1:
this example prepares 8-benzenesulfonyl substituted flavonol (3-hydroxy-2- (4-methoxyphenyl) -5, 7-dimethyl-8-tosyl-4H-chromen-4-one) having the formula 1:
the preparation method comprises the following steps: to a 250mL single neck flask equipped with a magnetic stir bar were added 2- (4-methoxyphenyl) -5, 7-dimethyl-8- (p-tolylthio) -4H-chromen-4-one (structural formula 1-1) (1.0mmol,420.0mg) and a mixed organic solvent (37.0mL, dichloromethane/acetone ═ 21/16 mL).
After adding 30.0ml of buffer (sodium carbonate/sodium bicarbonate 8.0/3.8g in 200.0ml of water), the solution was stirred vigorously at room temperature. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise again, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise for a third time, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the mixture was allowed to stand for separation, the organic phase was separated, and the aqueous phase was extracted with DCM. The organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was then filtered, p-toluenesulfonic acid was added to the filtrate and stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure and recrystallized several times from acetone to obtain 8-benzenesulfonyl substituted flavonol represented by formula 1 in 53% yield. This material was a yellow solid. An X-ray diffraction tester is adopted to test the single crystal structure of the 8-benzenesulfonyl substituted flavonol to obtain a structure analytic diagram shown in figure 1.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.37(d,J＝9.1Hz,2H),7.74(d,J＝8.3Hz,2H),7.12-7.04(m,5H),6.99(s,1H),3.92(s,3H),2.94(s,3H),2.90(s,3H),2.28(s,3H)；13C-NMR(101MHz,CDCl3):δ＝173.6,161.1,154.4,146.3,145.8,144.7,144.1,139.6,137.8,131.6,130.4,129.4,126.7,125.6,122.6,118.5,114.0,55.4,23.1,22.8,21.5；HRMS for C25H22O6S(M+Na)+:Anal.Mass,473.1029,Found,473.1028.
example 2
This example prepares an 8-benzenesulfonyl substituted flavonol of formula 2:
the preparation method comprises the following steps: to a 250mL single neck flask equipped with a magnetic stir bar were added 2- (4-methoxyphenyl) -5, 7-dimethyl-8- (phenylthio) -4H-chromen-4-one (structure: formula 2-1) (1.0mmol,388.1mg) and a mixed organic solvent (37.0mL, dichloromethane/acetone ═ 21/16 mL).
After adding 30.0ml of buffer (sodium carbonate/sodium bicarbonate 8.0/3.8g in 200.0ml of water), the solution was stirred vigorously at room temperature. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise again, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise for a third time, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the mixture was allowed to stand for separation, the organic phase was separated, and the aqueous phase was extracted with DCM. The organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was then filtered, p-toluenesulfonic acid was added to the filtrate and stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure and recrystallized several times from acetone to obtain 8-benzenesulfonyl substituted flavonol represented by formula 2 in 59% yield. This material was a yellow solid.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.32(d,J＝8.9Hz,2H),7.85(d,J＝7.7Hz,2H),7.44(t,J＝7.5Hz,1H),7.28(d,J＝10.3Hz,2H),7.08(d,J＝8.6Hz,3H),3.92(s,3H),2.96(s,3H),2.91(s,3H)；13C-NMR(101MHz,CDCl3):δ＝173.6,161.1,154.4,146.6,146.0,144.8,142.5,137.8,133.1,131.6,130.3,128.8,126.6,125.1,122.5,118.5,113.9,55.4,23.1,22.8；HRMS for C24H20O6S(M+Na)+:Anal.Mass,459.0873,Found,459.0876.
example 3
This example prepared 8-benzenesulfonyl substituted flavonols of formula 3:
the preparation method comprises the following steps: to a 250mL single neck flask equipped with a magnetic stir bar were added 8- [ (4-bromophenyl) thio ] -2- (4-methoxyphenyl) -5, 7-dimethyl-4H-chromen-4-one (structure formula 3-1) (1.0mmol,466.0mg) and mixed organic solvents (37.0mL, dichloromethane/acetone ═ 21/16 mL).
After adding 30.0ml of buffer (sodium carbonate/sodium bicarbonate 8.0/3.8g in 200.0ml of water), the solution was stirred vigorously at room temperature. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise again, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise for a third time, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the mixture was allowed to stand for separation, the organic phase was separated, and the aqueous phase was extracted with DCM. The organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was then filtered, p-toluenesulfonic acid was added to the filtrate and stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure and recrystallized several times from acetone to obtain 8-benzenesulfonyl substituted flavonol represented by formula 3 in a yield of 57%. This material was a yellow solid.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.32(d,J＝9.1Hz,2H),7.71(d,J＝8.7Hz,2H),7.41(d,J＝8.7Hz,2H),7.16-7.05(m,3H),6.96(s,1H),3.93(s,3H),2.95(s,3H),2.91(s,3H)；13C-NMR(101MHz,CDCl3):δ＝173.5,161.2,154.3,146.9,145.9,144.7,141.4,137.9,132.1,131.7,130.3,128.3,124.8,122.4,118.6,114.0,55.4,23.1,22.8；HRMS forC24H19BrO6S(M+Na)+:Anal.Mass,536.9978,Found,536.9973.
example 4
This example prepares an 8-benzenesulfonyl substituted flavonol of formula 4:
the preparation method comprises the following steps: to a 250mL single neck flask equipped with a magnetic stir bar were added 8- [ (4-chlorophenyl) thio ] -2- (3, 4-dimethoxyphenyl) -5, 7-dimethyl-4H-chromen-4-one (structure formula 4-1) (1.0mmol,452.0mg) and a mixed organic solvent (37.0mL, dichloromethane/acetone ═ 21/16 mL).
After adding 30.0ml of buffer (sodium carbonate/sodium bicarbonate 8.0/3.8g in 200.0ml of water), the solution was stirred vigorously at room temperature. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise again, and the mixture was stirred at room temperature for 15 hours. Then an aqueous solution of potassium monopersulfate complex salt (7.3mmol,47.0ml) was slowly added dropwise for a third time, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the mixture was allowed to stand for separation, the organic phase was separated, and the aqueous phase was extracted with DCM. The organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was then filtered, p-toluenesulfonic acid was added to the filtrate and stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure and recrystallized several times from acetone to obtain 8-benzenesulfonyl substituted flavonol represented by formula 4 in a yield of 38%. This material was a yellow solid.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.16(d,J＝1.9Hz,1H),8.02(dd,J＝8.5,2.0Hz,1H),7.84(d,J＝8.7Hz,2H),7.28(d,J＝8.6Hz,2H),7.11-7.01(m,3H),4.04(s,3H),4.01(s,3H),2.93(s,3H),2.90(s,3H)；13C-NMR(101MHz,CDCl3):δ＝173.5,154.3,150.7,149.0,146.9,145.8,144.6,140.9,139.9,138.1,131.7,129.3,128.3,125.1,122.8,122.5,118.6,111.0,110.8,56.3,56.0,23.2,22.5；HRMS for C25H21ClO7S(M+Na)+:Anal.Mass,523.0589,Found,523.0577.
example 5
This example prepares an 8-phenylsulfonyl-substituted flavone glucoside having the formula 5:
the preparation method is that 3-hydroxy-2- (4-methoxyphenyl) -5, 7-dimethyl-8-tosyl-4H-chromen-4-one (structural formula 1 in example 1) (0.1mmol,45.0mg) and potassium carbonate (0.57mmol,79.1mg) are added to a 100mL single-necked flask equipped with a magnetic stirring bar under argon atmosphere, after 10mL of anhydrous acetone is added, the flask is sealed with a screw cap, and the solution is stirred at room temperature for 1 hour, bromoacetyl glucose (0.26mmol,100mg) is added to the mixture at room temperature, and the solution is stirred overnight, after filtration, the resulting solution is concentrated under reduced pressure, the crude product is subjected to silica gel column chromatography and eluted with a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 3:1), the eluent containing the target product is collected by TLC elution tracing, the eluates of the target product are combined, and evaporated and concentrated to obtain a glucose derivative of 8-phenylsulfonyl-substituted flavone (5, 7-dimethyl-8-tosyl-4' -p-O-methoxyacetyl-glucose- β% yield as yellow substance as an oily liquid.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.15(d,J＝8.9Hz,2H),7.63(d,J＝8.3Hz,2H),7.06(d,J＝2.9Hz,2H),7.03(s,1H),6.99(d,J＝8.2Hz,2H),5.47(d,J＝7.8Hz,1H),5.26(t,J＝9.5Hz,1H),5.16(dd,J＝9.7,7.9Hz,1H),5.04(t,J＝9.6Hz,1H),3.92(m,2H),3.94(s,3H),3.61(ddd,J＝12.2,6.7,4.1Hz,1H),2.95(s,3H),2.84(s,3H),2.26(s,3H),2.11(s,3H),2.00(s,3H),1.99(s,3H),1.92(s,3H)；13C-NMR(101MHz,CDCl3):δ＝174.5,170.4,170.0,169.9,169.5,161.6,156.5,154.4,146.5,145.3,144.1,139.3,136.0,132.2,131.6,129.2,127.0,125.9,122.0,121.7,113.4,98.9,72.5,71.5,68.3,61.5,55.4,29.3,23.0,22.9,21.4,20.9,20.6,20.6,20.5；HRMS for C39H40O15S(M+Na)+:Anal.Mass,803.1980,Found,803.1942.
5, 7-dimethyl-8-p-toluenesulfonyl-4' -methoxyflavone-3-O- β -acetylglucoside (structure formula 5-1) (0.07mmol,54.6mg) and anhydrous methanol (15mL) were added to a 100mL single-necked flask equipped with a magnetic stir bar, 1.4mL of aqueous ammonia (1.4mL) was added, the solution was stirred at room temperature for 12 hours, the solution was concentrated under reduced pressure, the crude product was subjected to silica gel column chromatography and eluted with a mixture of ethyl acetate and methanol (ethyl acetate: methanol: 5:1), the eluate containing the objective product was collected by TLC elution tracing detection, the eluates of the objective product were combined, and evaporated and concentrated to give 8-benzenesulfonyl-substituted flavone glucoside represented by formula 5 in 81% yield as a yellow solid.
Characterization data: 1H-NMR (400MHz, DMSO-d6): δ ═ 8.17(d, J ═ 9.0Hz,2H),7.69(d, J ═ 8.3Hz,2H),7.35(s,1H),7.19(d, J ═ 8.2Hz,2H),7.13(d, J ═ 9.0Hz,2H),5.43(d, J ═ 7.7Hz,1H),5.36(d, J ═ 4.6Hz,1H),5.07(d, J ═ 4.9Hz,1H),4.96(d, J ═ 5.0Hz,1H),4.29(t, J ═ 5.5Hz,1H),3.89(s,3H),3.54(dd, J ═ 11.4,5.6, 3.7H), 3.7.7H (d, 3.06H, 3.7H, 3.06(d, 2H, 3.7H, 3H, 2H, 7H, 3H, 2H, 3H, 7H, 2H, 3H, 7H, 2H, 3H, 2H, 3; 13C-NMR (101MHz, DMSO-d6): δ 174.8,161.7,154.6,154.1,146.5,145.6,144.7,139.6,136.7,132.5,131.6,130.0,126.7,125.2,122.1,121.6,114.0,101.0,78.0,76.9,74.6,70.2,61.1,55.9,30.0,22.9, 22.5; HRMS for C31H32O11S (M + Na) +: anal. Mass,635.1558, Found,635.1556.
Example 6
Example preparation of 8-benzenesulfonyl substituted flavone glucoside the structural formula of the glycoside is shown in formula 6:
the preparation method is that 3-hydroxy-2- (4-methoxyphenyl) -5, 7-dimethyl-8- (phenylsulfonyl) -4H-chromen-4-one (shown in formula 2 in example 2) (0.1mmol,43.6mg) and potassium carbonate (0.57mmol,79.1mg) are added to a 100mL single-necked flask equipped with a magnetic stirring bar under argon atmosphere, after 10mL of anhydrous acetone is added, the flask is sealed with a screw cap, and the solution is stirred at room temperature for 1 hour, bromoacetyl glucose (0.26mmol,100mg) is added to the mixture at room temperature, and the solution is stirred overnight, after filtration, the resulting solution is concentrated under reduced pressure, the crude product is subjected to silica gel column chromatography and eluted with a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 3:1), the eluent containing the target product is collected by TLC elution tracing, the eluates of the target product are combined, and evaporated and concentrated to obtain a glucose derivative of 8-phenylsulfonyl-substituted flavone (5, 7-dimethyl-8-phenylsulfonyl-4' -methoxy-3-O- β% yield of the yellow flavone as a yellow liquid, which is obtained as an oily substance.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.10(d,J＝9.0Hz,2H),7.73(d,J＝7.4Hz,2H),7.39(t,J＝7.5Hz,1H),7.20(t,J＝7.9Hz,2H),7.08(s,1H),7.03(d,J＝9.0Hz,2H),5.47(d,J＝7.9Hz,1H),5.27(t,J＝9.5Hz,1H),5.17(dd,J＝9.7,7.9Hz,1H),5.04(t,J＝9.7Hz,1H),3.93(s,3H),3.99-3.83(m,2H),3.69-3.62(m,1H),2.96(s,3H),2.82(s,3H),2.12(s,3H),2.00(s,3H),1.98(s,3H),1.92(s,3H)；13C-NMR(101MHz,CDCl3):δ＝174.4,170.4,170.0,170.0,169.5,161.6,156.6,154.4,146.7,145.5,142.1,136.0,133.1,132.2,131.6,128.6,126.8,125.4,121.9,121.7,113.4,98.9,72.5,71.4,68.3,61.4,55.4,29.3,23.0,22.9,20.9,20.6,20.6,20.5；HRMS for C38H38O15S(M+Na)+:Anal.Mass,789.1824,Found,789.1815.
to a 100mL single neck flask equipped with a magnetic stir bar were added 5, 7-dimethyl-8-phenylsulfonyl-4' -methoxyflavone-3-O- β -acetylglucoside (represented by formula 6-1) (0.07mmol,53.6mg) and anhydrous methanol (15mL), 1.4mL of aqueous ammonia (1.4mL) was added, the solution was stirred at room temperature for 12 hours, the solution was concentrated under reduced pressure, the crude product was subjected to silica gel column chromatography and eluted with a mixture of ethyl acetate and methanol (ethyl acetate: methanol: 5:1), followed by TLC elution, eluates containing the objective product were collected, the objective product eluates were combined, and evaporated and concentrated to give 8-phenylsulfonyl-substituted flavone glucoside represented by formula 6 in 50% yield as a yellow solid.
Characterization data:1H-NMR(400MHz,DMSO-d6):δ＝8.08(d,J＝9.0Hz,2H),7.72(d,J＝8.7Hz,2H),7.60(d,J＝8.6Hz,2H),7.38(s,1H),7.12(d,J＝9.0Hz,2H),5.42(d,J＝7.7Hz,1H),5.35(d,J＝4.5Hz,1H),5.09(s,1H),4.98(s,1H),4.29(t,J＝5.5Hz,1H),3.89(s,3H),3.55(dd,J＝11.3,5.2Hz,1H),3.20(s,1H),3.14-3.06(m,2H),3.05(s,1H),2.86(s,3H),2.80(s,3H),1.76(s,1H)；13C-NMR(101MHz,DMSO-d6):δ＝174.7,161.6,154.6,154.2,146.8,145.9,142.4,136.7,134.1,132.5,131.6,129.6,126.5,124.7,122.0,121.6,114.0,101.0,77.9,76.9,74.6,70.2,61.1,55.9,22.9,22.7；HRMS for C30H30O11S(M+Na)+:Anal.Mass,621.1401,Found,621.1393.
example 7
This example prepared an 8-benzenesulfonyl substituted flavone glucoside of formula 7:
the preparation method is that 8- [ (4-bromophenyl) sulfonyl ] -3-hydroxy-2- (4-methoxyphenyl) -5, 7-dimethyl-4H-benzopyran-4-one (formula 3 in example 3) (0.1mmol,51.4mg) and potassium carbonate (0.57mmol,79.1mg) are added to a 100mL single-neck flask equipped with a magnetic stirring bar under argon atmosphere, after 10mL of anhydrous acetone is added, the flask is sealed with a screw cap, and the solution is stirred at room temperature for 1 hour, bromoacetyl glucose (0.26mmol,100mg) is added to the mixture at room temperature, and the solution is stirred overnight, after filtration, the resulting solution is concentrated under reduced pressure, the crude product is subjected to silica gel column chromatography and eluted with a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate: 3:1), the eluent containing the target product is collected by TLC elution tracing, the eluates of the target product are combined, evaporated and concentrated to obtain a glucose derivative of 8-phenylsulfonyl-substituted flavone represented by formula 7-1 (5, 7-dimethyl-8-phenylsulfonyl-4' -methoxy-O-phenyl glycoside) as yellow substance, which is a yellow liquid, β% of the target product.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝8.09(d,J＝8.9Hz,2H),7.59(d,J＝8.6Hz,2H),7.32(d,J＝8.6Hz,2H),7.11-7.02(m,3H),5.47(d,J＝7.8Hz,1H),5.25(t,J＝9.5Hz,1H),5.14(dd,J＝9.7,7.9Hz,1H),5.03(t,J＝9.7Hz,1H),3.94(s,3H),4.00-3.81(m,2H),3.62-3.56(m,1H),2.94(s,3H),2.86(s,3H),2.10(s,3H),2.00(s,3H),1.99(s,3H),1.93(s,3H)；HRMS for C38H37BrO15S(M+Na)+:Anal.Mass,867.0920,Found,867.0929.
to a 100mL single-necked flask equipped with a magnetic stirring bar were added 5, 7-dimethyl-8-p-bromophenylsulfonyl-4' -methoxyflavone-3-O- β -acetylglucoside (represented by formula 7-1) (0.07mmol,59.0mg) and anhydrous methanol (15mL), 1.4mL of aqueous ammonia (1.4mL) was added, the solution was stirred at room temperature for 12 hours, the solution was concentrated under reduced pressure, the crude product was subjected to silica gel column chromatography and eluted with a mixture of ethyl acetate and methanol (ethyl acetate: methanol: 5:1), the eluates containing the objective product were collected by TLC elution tracing, the objective product eluates were combined, and evaporated and concentrated to give 8-phenylsulfonyl-substituted flavone glucose glycoside represented by formula 7 in 66% yield, which was a yellow solid.
Characterization data:1H-NMR(400MHz,DMSO-d6):δ＝7.93(d,J＝1.9Hz,1H),7.83(d,J＝8.7Hz,2H),7.75(dd,J＝8.6,2.0Hz,1H),7.50(d,J＝8.7Hz,2H),7.37(s,1H),7.18(d,J＝8.7Hz,1H),5.52(d,J＝7.6Hz,1H),5.37(d,J＝4.6Hz,1H),5.11(d,J＝4.9Hz,1H),4.98(d,J＝4.9Hz,1H),4.38(t,J＝5.4Hz,1H),3.90(s,3H),3.83(s,3H),3.56(dd,J＝11.4,5.6Hz,1H),3.29-3.18(m,1H),3.20-3.12(m,1H),3.07(d,J＝4.6Hz,2H),2.85(s,3H),2.80(s,3H),2.05-1.92(m,1H)；13C-NMR(101MHz,DMSO-d6):δ＝174.7,154.6,154.2,151.4,148.4,147.1,145.9,141.2,139.0,136.6,132.6,129.9,128.6,124.4,123.0,122.0,121.7,113.0,111.5,100.9,77.9,76.9,74.7,70.2,61.0,56.0,30.0,23.0,22.7；HRMS forC31H31ClO12S(M+Na)+:Anal.Mass,685.1117,Found,685.1103.
example 8
This example prepared an 8-benzenesulfonyl substituted flavone glucoside of formula 8:
the preparation method is that 8- [ (4-chlorophenyl) sulfonyl ] -2- (3, 4-dimethoxyphenyl) -3-hydroxy-5, 7-dimethyl-4H-benzopyran-4-one (formula 4 in example 4) (0.1mmol,50.0mg) and potassium carbonate (0.57mmol,79.1mg) are added to a 100mL single-neck flask equipped with a magnetic stirring bar under argon atmosphere, after 10mL of anhydrous acetone is added, the flask is sealed with a screw cap, and the solution is stirred at room temperature for 1 hour, bromoacetyl glucose (0.26mmol,100mg) is added to the mixture at room temperature, and the solution is stirred overnight, after filtration, the resulting solution is concentrated under reduced pressure, the crude product is subjected to silica gel column chromatography and eluted with a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 3:1), followed by TLC elution, the eluate containing the target product is collected, the target product eluates are combined and evaporated and concentrated to obtain the 8-benzenesulfonyl substituted flavone glucose derivative represented by formula 8-1 (5, 7-dimethyl-4-benzenesulfonyl-4' -methoxy-O-acetyl glucoside, yield, β% as a yellow substance.
Characterization data:1H-NMR(400MHz,CDCl3):δ＝7.90(d,J＝2.0Hz,1H),7.85(dd,J＝8.5,2.0Hz,1H),7.72(d,J＝8.7Hz,2H),7.19(d,J＝8.7Hz,2H),7.07(s,1H),7.03(d,J＝8.6Hz,1H),5.56(d,J＝7.9Hz,1H),5.28(t,J＝9.5Hz,1H),5.17(dd,J＝9.7,7.9Hz,1H),5.05(t,J＝9.7Hz,1H),4.06(s,3H),4.03(s,3H),4.01-3.89(m,2H),3.68-3.61(m,1H),2.94(s,3H),2.84(s,3H),2.11(s,3H),2.01(s,3H),1.99(s,3H),1.90(s,3H)；HRMS for C39H39ClO16S(M+Na)+:Anal.Mass,853.1540,Found,853.1525.
to a 100mL single-necked flask equipped with a magnetic stirring bar were added 5, 7-dimethyl-8-p-chlorobenzenesulfonyl-3 ', 4' -methoxyflavone-3-O- β -acetylglucoside (formula 8-1) (0.07mmol,58.1mg) and anhydrous methanol (15mL), 1.4mL of aqueous ammonia (1.4mL) was added, the solution was stirred at room temperature for 12 hours, the solution was concentrated under reduced pressure, the crude product was subjected to silica gel column chromatography and eluted with a mixture of ethyl acetate and methanol (ethyl acetate: methanol: 5:1), the eluates containing the target product were collected by TLC elution tracing, the target product eluates were combined, and evaporated and concentrated to give 8-benzenesulfonyl-substituted flavone glucoside represented by formula 8 in 69% yield.
Characterization data:1H-NMR(400MHz,DMSO-d6):δ＝8.08(d,J＝9.0Hz,2H),7.72(d,J＝8.7Hz,2H),7.60(d,J＝8.6Hz,2H),7.38(s,1H),7.12(d,J＝9.0Hz,2H),5.42(d,J＝7.7Hz,1H),5.35(d,J＝4.5Hz,1H),5.09(s,1H),4.98(s,1H),4.29(t,J＝5.5Hz,1H),3.89(s,3H),3.55(dd,J＝11.3,5.2Hz,1H),3.20(s,1H),3.14-3.06(m,2H),3.05(s,1H),2.86(s,3H),2.80(s,3H),1.76(s,1H)；13C-NMR(101MHz,DMSO-d6):δ＝174.7,161.7,154.6,154.2,147.0,146.0,141.7,136.8,132.7,132.5,131.5,128.5,128.0,124.2,122.0,121.7,114.1,101.0,78.0,76.9,74.6,70.2,61.2,55.9,23.0,22.6；HRMS for C30H29BrO11S(M+Na)+:Anal.Mass,699.0506,Found,699.0478.
finally, the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered in the claims of the present invention.
Claims (10)
1. An 8-benzenesulfonyl-substituted flavone glucoside, characterized by having the structure shown in formula III below:
wherein R is1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; (ii) a R2Including alkoxy substituted aryl groups.
2. The 8-benzenesulfonyl substituted flavone glucoside of claim 1,
the R is1Comprises that
The R is2Comprises that
3. The method for preparing 8-benzenesulfonyl substituted flavone glucoside of claim 1, wherein said method comprises: dissolving 8-benzenesulfonyl substituted flavonol and alkali in an organic solvent in an inert gas atmosphere, and adding a glucose derivative for reaction to obtain the 8-benzenesulfonyl substituted flavone glucose glucoside derivative; the 8-benzenesulfonyl substituted flavone glucoside derivative is hydrolyzed under alkaline conditions to obtain the 8-benzenesulfonyl substituted flavone glucoside.
4. The method for preparing 8-benzenesulfonyl substituted flavone glucose glycoside according to claim 3, wherein said 8-benzenesulfonyl substituted flavonol has a structure shown in formula I
Wherein R is1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; r2Including alkoxy substituted aryl groups.
5. The method for preparing 8-phenylsulfonyl-substituted flavone glucoside of claim 3 or 4, wherein R in the structure of 8-phenylsulfonyl-substituted flavonol1Comprises that
R in the structure of the 8-benzenesulfonyl substituted flavonol2Comprises that
6. The method for preparing 8-benzenesulfonyl substituted flavone glucoside of claim 3 or 4, wherein said 8-benzenesulfonyl substituted flavonol is prepared by: dissolving flavonoid shown in formula II in a mixed organic solvent, and carrying out a first-step reaction under the action of a buffer solution and an oxidant; in the formula II R1Including unsubstituted C6-10 aryl, halogen, alkyl or alkoxy substituted aryl; r2Including alkoxy-substituted aryl groups;
and after the first step of reaction is finished, adding organic acid to carry out a second step of reaction to obtain the 8-benzenesulfonyl substituted flavonol.
7. The method for preparing an 8-benzenesulfonyl substituted flavone glucoside of claim 6, wherein said buffer comprises an inorganic base solution, preferably NaHCO3And Na2CO3An aqueous solution of (a);
the oxidant comprises an inorganic oxidant, preferably potassium hydrogen peroxymonosulfate composite salt water solution;
the mixed organic solvent comprises a mixture of dichloromethane and acetone, a mixture of toluene and acetone, a mixture of tetrahydrofuran and acetone, a mixture of acetonitrile and acetone, a mixture of dichloroethane and acetone, a mixture of carbon tetrachloride and acetone, a mixture of chloroform and acetone, and a mixture of hexafluoroisopropanol and acetone;
the organic acid comprises p-toluenesulfonic acid and caprylic acid;
the reaction temperature of the first step and the reaction temperature of the second step are both 15-35 ℃, and the reaction time of the first step and the reaction time of the second step are 40-50 hours.
8. The method for preparing 8-benzenesulfonyl substituted flavone glucoside of claim 6, wherein the ratio of the flavonoid represented by formula II to the oxidant is 1: 5-25; the adding amount of the organic solvent is 30-40 mL/mmol based on the amount of the flavonoid substance shown in the formula II.
9. The process for preparing an 8-benzenesulfonyl substituted flavone glucoside of claim 3, wherein the base is an inorganic base, preferably the base comprises potassium carbonate, potassium acetate, potassium phosphate, sodium carbonate;
the glucose derivative comprises halogenated acetyl glucose, preferably the glucose derivative comprises bromoacetyl glucose and chloroacetyl glucose;
the organic solvent comprises dichloromethane, toluene, tetrahydrofuran, acetonitrile, dichloroethane and acetone.
10. The method for preparing 8-benzenesulfonyl substituted flavone glucoside of claim 3, wherein the reaction temperature is 15-35 ℃ and the reaction time is 12-14 h; the mass ratio of the 8-benzenesulfonyl substituted flavonol to the alkali to the glucose derivative is 1: 5.4-6.0: 2.4-3.0; the amount of the organic solvent added is 80-100 mL/mmol based on the amount of the 8-benzenesulfonyl-substituted flavonol.
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| WO2015166041A1 (en) * | 2014-05-01 | 2015-11-05 | De Montfort University | Flavones as cyp1a1 inhibitors for the treatment of cancer |
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| CN101124212A (en) * | 2004-12-21 | 2008-02-13 | 弗·哈夫曼-拉罗切有限公司 | Senman derivatives and their use as 5-HT receptor ligands |
| WO2015166041A1 (en) * | 2014-05-01 | 2015-11-05 | De Montfort University | Flavones as cyp1a1 inhibitors for the treatment of cancer |
| CN105481919A (en) * | 2014-09-18 | 2016-04-13 | 贵州百灵企业集团制药股份有限公司 | Flavone glycoside derivatives, and preparation method and application thereof |
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