CN101812068A - Bergenin derivative and preparation method thereof - Google Patents

Bergenin derivative and preparation method thereof Download PDF

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CN101812068A
CN101812068A CN 201010129152 CN201010129152A CN101812068A CN 101812068 A CN101812068 A CN 101812068A CN 201010129152 CN201010129152 CN 201010129152 CN 201010129152 A CN201010129152 A CN 201010129152A CN 101812068 A CN101812068 A CN 101812068A
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bergeninum
nmr
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刘建平
陈静波
刘娜娜
张洪彬
羊晓东
赵静峰
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Yunnan University YNU
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Yunnan University YNU
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Abstract

The invention relates to a bergenin derivative and a preparation method thereof by using bergenin and benzyl halide as main materials, comprising the following steps: firstly preparing phenolic hydroxyl group protected bergenin compound; amending and altering alcoholic hydroxyl group to synthesize a series of bergenin derivatives; the synthesis method based on easily-obtained natural products is simple and convenient, and has better operability and reaction yield; and the invention provides scientific evidence for discussing new use of bergenin, and has important meanings for the research and development of new medicine.

Description

Bergeninum analog derivative and preparation method thereof
Technical field: the present invention relates to the novel compound that contains the plain structure of Rhizome or herb of Purple Bergenia, its preparation method is that composition of active components is in the application aspect the medicine with this compounds.
Background technology: Bergeninum extensively is present in the various plants, because its wide biological activity receives vegetable chemistry, pharmaceutical chemistry and pharmacologist's concern.Bergeninum is except that being mainly used in clinically the cough-relieving, also have anti-inflammatory, antimycotic, antiviral, protect the liver the anti AIDS virus isoreactivity, even also sacroiliitis and ulcer are had effect.Therefore, Bergeninum is furtherd investigate, particularly it is carried out the structural modification transformation, study the physiologically active of its analogue, derivative, the research and development for new drug are of great importance.
Among the present invention be with the Bergeninum raw material synthetic Bergeninum compounds, derivative and preparation method thereof up to now document do not appear in the newspapers.
Summary of the invention:
The invention provides a series of Bergeninum analog derivatives and preparation method thereof; with main raw materials such as Bergeninum, benzyl halogenide; at first prepare the Bergeninum compound of phenolic hydroxyl group protection, on this basis its alcoholic extract hydroxyl group is modified transformation, synthesized a series of Bergeninum analog derivatives.
Bergeninum analog derivative provided by the invention is represented with following general structure (I):
Figure GSA00000065338900011
(1) work as R=Bn, Me, during Et, R '=OH
(2) when R=Bn, R '=OTs, OMs, OTBS, I, Br, Cl, NHBn, NHCH 2Ph (OCH 3)-4, NHCH 2Ph (I)-4, NHCH 2Ph (Br)-4, NHCH 2Ph (Cl)-4,
A kind of preparation feedback formula of the Bergeninum analog derivative with general structure (I) is as follows:
Figure GSA00000065338900022
Above-mentioned preparation method's step is as follows:
(1), the protection of Bergeninum phenolic hydroxyl group:
With Bergeninum, halogenation benzyl or methyl halide/ethane and salt of wormwood is raw material, and the mole number ratio of raw material is 1/2～5/6～10, adds N, dinethylformamide, raw material is dissolved fully after, room temperature to 60 ℃ stirring reaction 24～72 hours.Evaporated under reduced pressure N, add ethyl acetate and water (ratio is 3/1) behind the dinethylformamide, after telling organic layer, water layer ethyl acetate extraction 3～5 times, merge organic phase, be washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent gets white powder solid product (yield: 95～100%).
(2), the reaction of Bergeninum alcoholic extract hydroxyl group:
With step (1) product, corresponding muriate and alkali (pyridine, tertiary amine or salt of wormwood) is raw material, and the mole number ratio of raw material is 1/2～3/5～8, add after methylene dichloride dissolves raw material fully, in 0 ℃ to stirring at room reaction 24～72 hours.Add methylene dichloride and water (volume ratio is 3/1) behind evaporated under reduced pressure pyridine or the tertiary amine, tell organic layer after, water layer is with dichloromethane extraction 3～5 times, merge organic phase, be washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent gets crude product.Silica gel column chromatography (petrol ether/ethyl acetate=3: 1～1: 1) gets white solid pulverulent solids product (yield: 75～95%).
(3), the halid preparation of Bergeninum:
Methanesulfonates that generates with step (2) or p-toluenesulfonic esters and sodium halide/potassium halide are raw material, and the mole number ratio of raw material is 1/1～3, is solvent refluxing reaction 3～5 days with acetone.Methylene dichloride dissolving behind the evaporated under reduced pressure acetone, solids removed by filtration, the evaporate to dryness methylene dichloride gets crude product.Silica gel column chromatography (petrol ether/ethyl acetate=3: 1～1: 1) gets white solid powder (yield: 80～90%).
(4), the preparation of Bergeninum derivative:
With the methanesulfonates/p-toluenesulfonic esters of step (2) generation or the halogenide and the nitrogenous compound R ' H of step (3) generation is raw material, and the mole number ratio of raw material is 1/1～5, and with N, dinethylformamide is 90 ℃～back flow reaction of solvent 20～60 hours.Evaporated under reduced pressure N adds methylene dichloride and water (volume ratio is 3/1) behind the dinethylformamide, tell organic layer after, water layer dichloromethane extraction 3～5 times merge organic phase, are washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent gets crude product.Silica gel column chromatography (ethyl acetate/ethanol=20: 1～3: 1) gets white solid powdery product (yield: 70～98%).
(5), Bergeninum derivative debenzylation:
With step (4), generate contain the benzyl product be dissolved in methyl alcohol (5～20mg/mL), add palladium-carbon catalyst (consumption be raw materials quality 5～20%), 20～50 ℃ of reactions are 20～60 hours under the nitrogen atmosphere.Remove by filter catalyzer, evaporated under reduced pressure methyl alcohol gets crude product.Silica gel column chromatography (ethyl acetate/methanol=15: 1～3: 1) gets white solid powdery product (yield: 50～98%).
The invention provides a kind of structural modification remodeling method of common medicine Bergeninum, synthesized the Bergeninum analog derivative of a series of novel structures, the synthetic method of this compounds is not appeared in the newspapers as yet.The natural product of this synthetic method from being easy to get, simple synthetic method has better operability and reaction yield.The present invention provides scientific basis for inquiring into the new purposes of Bergeninum, and is significant to the research and development of new drug.
Embodiment: enumerate typical compound of the present invention below in conjunction with example.
Embodiment 1 benzyl Bergeninum
Figure GSA00000065338900041
Preparation process such as step (1), yield 99%.
1H?NMR(300MHz，CDCl 3)：δ7.87(1H，s)，7.82(2H，d，J＝7.5Hz)，7.61(2H，d，J＝7.5Hz)，7.45-7.32(6H，m)，5.44-5.32(2H，q，J＝11.1Hz)，5.19(2H，s)，5.04(1H，d，J＝9.9Hz)，4.59-4.41(5H，m)，4.05-4.03(1H，m)，3.96(3H，s).
13C-NMR(75MHz，CDCl 3)：δ164.22，152.69，150.85，148.95，138.53，136.79，128.69，128.35，128.18，127.80，127.64，120.01，111.52，82.58，81.37，75.73，75.43，72.43，71.15，70.78，61.84，60.86.。
Embodiment 2 methyl Bergeninums
Figure GSA00000065338900042
Preparation process such as step (1), yield 97%.
1H?NMR(300MHz，CDCl 3)：δ7.88(1H，s)，5.05(1H，d，J＝9.9Hz)，4.61-4.43(5H，m)，4.06-4.04(1H，m)，3.98(3H，s)，3.88(6H，s).
13C-NMR(75MHz，CDCl 3)：δ163.56，151.50，149.23，148.65，127.84，119.45，110.64，80.34，76.56，74.29，73.43，71.74，62.54，61.11，56.26.
Embodiment 3 ethyl Bergeninums
Figure GSA00000065338900043
Preparation process such as step (1), yield 96%.
1H?NMR(300MHz，CDCl 3)：δ7.86(1H，s)，5.03(1H，d，J＝9.8Hz)，4.58-4.41(5H，m)，4.09-4.07(1H，m)，4.03(2H，q，J＝19.7Hz)，4.01(2H，q，J＝19.3Hz)，3.98(3H，s)，3.88(6H，s).1.26(3H，t，J＝19.7Hz)，1.23(3H，t，J＝19.3Hz).
13C-NMR(75MHz，CDCl 3)：δ163.98，151.65，149.44，148.75，127.33，119.21，110.45，80.88，76.43，74.11，73.89，71.33，65.28，65.05，60.11.15.07，13.19。
Embodiment 4 benzyl Bergeninum tosic acid ester derivatives
Figure GSA00000065338900051
Preparation process such as step (1), (2), yield 93%.
1H-NMR(300MHz，CDCl 3)，δ：7.72(2H，d，J＝8.4Hz)，7.53(1H，s)，7.44-7.20(12H，m)，5.17-5.08(2H，q，J＝15.6Hz)，5.03-4.92(2H，q，J＝21.9Hz)，4.55(1H，d，J＝9.6Hz)，4.35-4.30(1H，dd，J1＝11.4Hz，J2＝11.1Hz)，4.11-3.91(3H，m)，3.89(3H，s)，3.74-3.68(1H，m)，3.61(1H，d，J＝8.4Hz)，2.35(3H，s).
13C-NMR(75MHz，CDCl 3)，δ：164.04，152.87，150.35，149.46，144.89，137.71，136.00，132.76，129.85，128.66，128.32，127.93，127.79，127.55，126.39，118.67，111.73，79.48，77.82，75.87，74.44，72.19，71.09，69.40，68.29，61.17，21.59.
Embodiment 5 benzyl Bergeninum mesylate derivatives
Figure GSA00000065338900052
Preparation process such as step (1), (2), yield 93%.
1H-NMR(300MHz，CDCl 3)：δ7.74(2H，d，J＝7.8Hz)，7.61(2H，d，J＝7.8Hz)，7.55(1H，s)，7.43-7.29(6H，m)，5.41-5.33(2H，q，J＝15.1Hz)，5.17(2H，s)，5.03(1H，d，J＝9.9Hz)，4.57-4.40(5H，m)，4.04-4.02(1H，m)，3.96(3H，s)，2.95(3H，s).
13C-NMR(75MHz，CDCl 3)：δ164.43，151.59，150.75，148.91，138.34，135.66，129.25，128.23，128.08，127.32，127.33，119.87，111.23，82.33，81.31，75.18，75.55，72.41，70.12，70.11，62.86，61.85，37.95.
Embodiment 6 benzyl Bergeninum tertiary butyl dimethyl-silicon ether derivants
Preparation process such as step (1), (2), yield 85%.
1H-NMR(300MHz，CDCl 3)：δ7.78(2H，d，J＝7.8Hz)，7.63(2H，d，J＝7.8Hz)，7.52(1H，s)，7.38-7.27(6H，m)，5.40-5.31(2H，q，J＝15.1Hz)，5.16(2H，s)，5.01(1H，d，J＝9.9Hz)，4.55-4.39(5H，m)，4.03-4.01(1H，m)，3.95(3H，s)，1.12(9H，s)，0.08(6H，s)，.
13C-NMR(75MHz，CDCl 3)：δ165.21，152.33，150.22，148.54，139.14，134.56，129.11，128.09，127.95，127.13，127.00，119.77，111.75，82.35，81.68，75.38，75.64，72.33，70.11，70.07，62.85，61.74，25.88，18.12，-5.72.
Embodiment 7 benzyl Bergeninum iodo derivatives
Figure GSA00000065338900062
Preparation process such as step (1)～(3), yield 87%.
1H-NMR(300MHz，CDCl 3)：δ7.48-7.26(11H，m)，5.11-5.04(4H，m)，4.68(1H，d，J＝10.2Hz)，4.04-3.81(5H，m)，3.49-3.38(2H，m)，3.16(1H，d，J＝10.8Hz)，2.94(1H，d，J＝9.0Hz).
13C-NMR(75MHz，CDCl 3)：δ164.69，152.80，150.31，149.69，138.01，135.91，128.63，128.27，127.69，127.50，127.10，126.78，118.63，111.73，80.07，77.15，75.56，74.00，73.75，71.69，71.06，61.20，8.07.
Embodiment 8 benzyl Bergeninum bromo derivatives
Figure GSA00000065338900071
Preparation process such as step (1)～(3), yield 80%.
1H-NMR(300MHz，CDCl 3)：δ7.48-7.26(11H，m)，5.11-5.04(4H，m)，4.78(1H，d，J＝10.1Hz)，4.05-3.85(5H，m)，3.50-3.44(2H，m)，3.56(1H，d，J＝10.5Hz)，3.31(1H，d，J＝10.5Hz).
13C-NMR(75MHz，CDCl 3)：δ165.12，152.96，150.65，149.89，138.64，135.99，128.87，128.50，127.86，127.53，127.89，126.94，118.37，111.43，80.75，77.89，76.32，74.56，73.84，71.79，71.35，61.55，32.55.
Embodiment 9 benzyl Bergeninum chlorinated derivatives
Preparation process such as step (1)～(3), yield 72%.
1H-NMR(300MHz，CDCl 3)：δ7.49-7.26(11H，m)，5.12-5.05(4H，m)，4.79(1H，d，J＝10.0Hz)，4.05-3.87(5H，m)，3.51-3.46(2H，m)，3.64(1H，d，J＝10.8Hz)，3.39(1H，d，J＝10.8Hz).
13C-NMR(75MHz，CDCl 3)：δ165.21，152.88，150.96，149.91，138.75，136.05，128.89，128.86，127.54，127.33，127.12，126.99，118.65，111.34，80.21，77.92，76.54，74.76，73.94，71.92，71.43，61.61，43.62.
Embodiment 10 benzyl Bergeninum benzyl amine derivatives
Preparation process such as step (1)～(4), yield 84%.
1H-NMR(300MHz，CDCl 3)：δ7.52-7.19(16H，m)，5.15-4.90(4H，m)，4.53(1H，d，J＝10.2Hz)，4.08-3.91(7H，m)，3.67-3.56(4H，m)，2.92-2.81(2H，m).
13C-NMR(75MHz，CDCl 3)：δ164.09，152.78，150.25，149.24，139.20，137.62，136.10，128.73，128.57，128.51，128.25，128.05，127.75，127.62，127.26，126.81，119.03，111.78，80.11，78.10，75.72，74.45，74.06，72.36，71.10，61.32，53.77，51.03.
Embodiment 11 benzyl Bergeninum 4-Methoxybenzylamine derivatives
Figure GSA00000065338900082
Preparation process such as step (1)～(4), yield 80%.
1H-NMR(300MHz，CDCl 3)：δ7.55-7.23(11H，m)，6.96(2H，d，J＝8.4Hz)，6.64(2H，d，J＝8.4Hz)，5.14-4.91(4H，m)，4.55(1H，d，J＝10.2Hz)，4.10-3.93(7H，m)，3.86(3H，s)，3.68-3.59(4H，m)，2.94-2.83(2H，m).
13C-NMR(75MHz，CDCl 3)：δ164.12，154.56，152.56，150.35，149.87，139.12，137.57，136.87，129.15，128.77，128.52，128.14，127.58，127.29，126.53，119.21，114.51，111.77，80.15，78.32，75.77，74.96，74.14，72.49，71.13，61.33，55.95，53.75，51.08。
Embodiment 12 benzyl Bergeninums are to the bretylium derivative
Figure GSA00000065338900091
Preparation process such as step (1)～(4), yield 80%.
1H-NMR(300MHz，CDCl 3)：δ7.56-7.21(13H，m)，6.95(2H，d，J＝8.4Hz)，5.13-4.90(4H，m)，4.53(1H，d，J＝10.2Hz)，4.08-3.90(7H，m)，3.66-3.57(4H，m)，2.92-2.81(2H，m).
13C-NMR(75MHz，CDCl 3)：δ164.09，152.89，150.31，149.87，139.12，137.57，136.87，131.52，130.44，128.65，128.48，128.08，127.55，127.32，126.78，121.41，119.25，111.45，80.19，78.46，75.72，74.91，74.55，72.71，71.16，61.35，53.73，51.04.
Embodiment 13 benzyl Bergeninums are to the chlorobenzylamine derivative
Figure GSA00000065338900092
Preparation process such as step (1)～(4), yield 77%.
1H-NMR(300MHz，CDCl 3)：δ7.52-7.17(13H，m)，6.99(2H，d，J＝8.4Hz)，5.11-4.92(4H，m)，4.52(1H，d，J＝10.2Hz)，4.07-3.89(7H，m)，3.65-3.56(4H，m)，2.90-2.80(2H，m).
13C-NMR(75MHz，CDCl 3)：δ164.07，152.77，150.30，149.57，139.23，137.78，136.44，132.86，129.58，128.77，128.54，128.06，127.35，127.21，126.68，121.42，119.55，111.38，80.20，78.57，75.18，74.82，74.73，72.78，71.42，61.67，53.72，51.07.
Embodiment 14 benzyl Bergeninum imdazole derivatives
Preparation process such as step (1)～(4), yield 83%.
1H-NMR(300MHz，CDCl 3)：δ7.59(1H，s)，7.51-6.95(13H，m)，5.18-5.04(4H，m)，4.24-4.15(2H，m)，3.98-3.83(6H，m)，3.54(1H，d，J＝8.1Hz)，3.04(1H，t，J＝8.4Hz).
13C-NMR(75MHz，CDCl 3)：δ164.06，152.92，150.35，149.32，138.68，137.41，136.07，128.80，128.57，128.40，128.30，128.03，127.67，126.58，120.89，118.76，111.78，79.72，78.92，75.40，74.64，72.47，71.22，69.97，61.42，47.38.
Embodiment 15 benzyl Bergeninum glyoxal ethyline derivatives
Figure GSA00000065338900102
Preparation process such as step (1)～(4), yield 74%.
1H-NMR(300MHz，CDCl 3)：δ7.49-7.23(10H，m)，7.01(3H，s)，6.83(1H，s)，5.18-5.08(2H，q，J＝19.5Hz)，4.99-4.86(2H，q，J＝27.0Hz)，4.01-3.94(6H，m)，3.87(1H，t，J＝9.0Hz)，3.77(1H，t，J＝9.0Hz)，3.61(2H，s)，3.48(1H，d，J＝9.3Hz)，3.77(1H，t，J＝9.0Hz)，2.36(3H，s).
13C-NMR(75MHz，CDCl 3)：δ164.00，152.97，149.99，149.31，146.15，137.16，136.11，128.83，128.69，128.50，127.68，126.69，126.32，121.03，118.70，111.78，79.60，75.50，74.78，72.40，71.27，70.68，61.39，46.59，12.84.
Embodiment 16 benzyl Bergeninum 2-ethyl imidazol(e) derivatives
Figure GSA00000065338900111
Preparation process such as step (1)～(4), yield 82%.
1H-NMR(300MHz，CDCl 3)：δ7.50(1H，s)，7.46-7.34(5H，m)，7.28-7.20(3H，m)，7.09(1H，s)，6.96-6.90(3H，m)，5.20-5.10(2H，q，J＝19.8Hz)，4.99-4.85(2H，q，J＝29.4Hz)，4.14-3.99(5H，m)，3.90-3.83(2H，m)，3.77(1H，t，J＝8.4Hz)，3.45-3.44(1H，m)，3.25(1H，t，J＝8.7Hz)，2.78-2.73(2H，m)，1.28(3H，t，J＝7.5Hz).
13C-NMR(75MHz，CDCl 3)：δ164.05，152.93，150.62，149.93，149.27，137.04，136.07，128.80，128.43，127.65，126.76，126.57，121.01，118.62，111.71，79.80，79.56，75.44，74.69，72.29，71.22，70.92，61.34，46.33，19.83，12.24.
Embodiment 17 benzyl Bergeninums 4,5-methylimidazole derivative
Figure GSA00000065338900112
Preparation process such as step (1)～(4), yield 70%.
1H-NMR(300MHz，CDCl 3)：δ7.60(1H，s)，7.52-6.99(11H，m)，5.20-5.06(4H，m)，4.26-4.17(2H，m)，3.97-3.81(6H，m)，3.52(1H，d，J＝8.2Hz)，3.03(1H，t，J＝8.2Hz)，2.18(6H，s).
13C-NMR(75MHz，CDCl 3)：δ164.03，152.55，150.31，149.66，138.64，137.12，136.56，132.45，129.03，128.87，128.21，128.10，128.02，127.66，126.34，118.71，111.70，79.22，78.55，75.41，74.63，72.46，71.65，69.53，61.22，47.37，13.23，10.51.
Embodiment 18 benzyl Bergeninum benzimidizole derivatives
Figure GSA00000065338900121
Preparation process such as step (1)～(4), yield 75%.
1H-NMR(300MHz，CDCl 3)：δ8.11(1H，s)，7.68-6.88(15H，m)，5.12-4.81(4H，m)，4.27(2H，s)，4.00(3H，s)，3.95(1H，d，J＝9.9Hz)，3.84-3.69(2H，m)，3.57(1H，d，J＝9.0Hz)，3.21(1H，t，J＝9.0Hz).
13C-NMR(75MHz，CDCl 3)：δ164.13，152.76，149.85，149.13，145.09，142.62，137.51，136.96，136.01，134.41，130.27，128.70，128.56，128.37，127.59，126.64，122.97，122.34，119.60，118.49，111.54，110.88，79.48，78.57，75.48，74.49，72.17，71.10，70.76，61.33，45.50.
Embodiment 19 benzyl Bergeninum dimethoxy benzimidizole derivatives
Preparation process such as step (1)～(4), yield 77%.
1H-NMR(300MHz，CDCl 3)：δ8.09(1H，s)，7.68-6.88(13H，m)，5.10-4.80(4H，m)，4.26(2H，s)，3.99(3H，s)，3.93(1H，d，J＝9.8Hz)，3.82-3.68(2H，m)，3.78(3H，s)，3.75(3H，s)，3.55(1H，d，J＝9.0Hz)，3.19(1H，t，J＝9.0Hz).
13C-NMR(75MHz，CDCl 3)：δ164.19，152.55，149.42，149.89，145.11，144.65，142.56，142.33，137.67，136.32，136.19，134.56，130.28，128.72，128.55，128.23，127.89，126.33，119.65，111.55，110.81，102.25，79.53，78.52，75.26，74.64，72.76，71.13，70.56，61.72，56.23，56.04，45.98.
Embodiment 20 benzyl Bergeninum dimethylbenzimidazole derivatives
Figure GSA00000065338900131
Preparation process such as step (1)～(4), yield 77%.
1H-NMR(300MHz，CDCl 3)：δ8.08(1H，s)，7.66-6.85(13H，m)，5.09-4.79(4H，m)，4.24(2H，s)，3.97(3H，s)，3.91(1H，d，J＝9.8Hz)，3.81-3.69(2H，m)，3.53(1H，d，J＝9.0Hz)，3.17(1H，t，J＝9.0Hz)，2.21(3H，s)，2.08(3H，s).
13C-NMR(75MHz，CDCl 3)：δ164.06，152.50，149.33，149.21，145.09，142.19，137.25，136.43，136.29，134.88，130.85，130.52，130.56，128.85，128.58，128.32，127.76，126.45，115.25，111.43，110.98，79.73，78.53，75.52，74.97，72.72，71.19，70.53，61.53，45.93，20.45，19.82.
Embodiment 21 benzyl Bergeninum methyl piperazine derivates
Figure GSA00000065338900132
Preparation process such as step (1)～(4), yield 75%.
1H-NMR(300MHz，CDCl 3)：δ7.54(1H，s)，7.43-7.28(10H，m)，5.17-4.94(4H，m)，4.55(1H，d，J＝10.5Hz)，4.08(1H，t，J＝9.9Hz)，3.93-3.88(4H，m)，3.61-3.47(2H，m)，2.64-2.25(13H，m).
13C-NMR(75MHz，CDCl 3)：δ163.69，152.83，150.28，149.24，137.84，136.03，128.68，128.45，128.27，128.00，127.54，127.44，126.53，119.15，111.71，79.93，76.73，75.65，74.07，73.98，72.45，71.06，61.66，61.26，54.80，53.87，45.75.
Embodiment 22 benzyl Bergeninum ethyl piperazidine derivatives
Figure GSA00000065338900141
Preparation process such as step (1)～(4), yield 70%.
1H-NMR(300MHz，CDCl 3)：δ7.56(1H，s)，7.45-7.25(10H，m)，5.15-4.94(4H，m)，4.56(1H，d，J＝10.2Hz)，4.10(1H，t，J＝9.9Hz)，3.94-3.90(4H，m)，3.59(1H，t，J＝9.0Hz)，3.51-3.48(1H，m)，2.66-2.02(12H，m)，1.06(3H，t，J＝7.2Hz).
13C-NMR(75MHz，CDCl 3)：δ163.67，152.92，150.35，149.34，137.84，136.07，128.75，128.52，128.34，128.11，127.60，127.55，126.55，119.20，111.81，79.93，76.97，75.80，74.10，73.84，72.52，71.13，61.95，61.34，54.15，52.66，52.20，11.95.
Embodiment 23 benzyl Bergeninum Phenylpiperazine derivatives
Preparation process such as step (1)～(4), yield 78%.
1H-NMR(300MHz，CDCl 3)：δ7.58(1H，s)，7.44-7.30(10H，m)，7.08(2H，dd，J1＝8.4Hz，J2＝8.0Hz)，6.64(1H，m)，6.60(2H，d，J＝8.4Hz)，5.19-4.95(4H，m)，4.57(1H，d，J＝10.4Hz)，4.10(1H，t，J＝9.9Hz)，3.93-3.88(4H，m)，3.61-3.47(2H，m)，2.68-2.27(10H，m).
13C-NMR(75MHz，CDCl 3)：δ163.65，152.32，150.11，149.65，149.20，137.23，136.01，129.78，128.63，128.25，128.13，128.01，127.23，127.05，126.65，119.17，118.29，114.53，111.21，79.89，76.65，75.34，74.01，73.57，72.32，71.01，61.36，61.17，54.56，53.43.
Embodiment 24 benzyl Bergeninum fluorophenyl bridged piperazine derivatives
Preparation process such as step (1)～(4), yield 74%.
1H-NMR(300MHz，CDCl 3)：δ7.58(1H，s)，7.47-7.33(10H，m)，7.07-6.88(4H，m)，5.16-4.98(4H，m)，4.59(1H，d，J＝10.5Hz)，4.14(1H，t，J＝9.9Hz)，4.02-3.96(4H，m)，3.65(1H，t，J＝9.0Hz)，3.57-3.54(1H，m)，3.06(4H，s)，2.82-2.78(2H，m)，2.63-2.53(4H，m).
13C-NMR(75MHz，CDCl 3)：δ163.70，157.36，154.11，152.90，150.32，149.30，139.67，139.56，137.87，136.05，128.73，128.53，128.33，128.09，127.59，127.50，126.50，124.58，122.95，122.84，119.15，116.33，116.06，111.77，79.84，76.73，75.75，74.07，72.51，71.09，61.85，61.33，54.23，50.43.
Embodiment 25 benzyl Bergeninum dimethylamino-propyl bridged piperazine derivatives
Figure GSA00000065338900161
Preparation process such as step (1)～(4), yield 65%.
1H-NMR(300MHz，CDCl 3)：δ7.51(1H，s)，7.41-7.26(10H，m)，5.11-4.92(4H，m)，4.52(1H，d，J＝10.2Hz)，4.05(1H，d，J＝9.9Hz)，3.90-3.83(4H，m)，3.57-3.47(2H，m)，2.58-2.34(20H，m)，1.73-1.71(2H，m).
13C-NMR(75MHz，CDCl 3)：δ163.70，152.78，150.27，149.20，137.79，135.99，128.66，128.43，128.25，127.98，127.51，127.47，126.57，119.12，111.66，79.94，76.73，75.71，74.25，73.96，72.45，71.03，61.65，61.24，57.30，55.95，53.92，52.95，44.75，23.99.
Embodiment 26 benzyl Bergeninum hydroxyethyl propyl group bridged piperazine derivatives
Figure GSA00000065338900162
Preparation process such as step (1)～(4), yield 75%.
1H-NMR(300MHz，CDCl 3)：δ7.57(1H，s)，7.46-7.27(10H，m)，5.16-4.96(4H，m)，4.56(1H，d，J＝10.2Hz)，4.10(1H，t，J＝10.2Hz)，3.96-3.90(4H，m)，3.64-3.48(5H，m)，2.64-2.44(12H，m).
13C-NMR(75MHz，CDCl 3)：δ163.75，152.91，150.32，149.33，137.90，136.05，128.75，128.52，128.35，128.06，127.61，127.50，126.52，119.13，111.81，79.90，76.73，75.76，74.05，72.52，71.13，61.76，61.34，59.36，57.98，54.10，52.78.
Embodiment 27 benzyl Bergeninum ethyl formate based piperazine derivatives
Figure GSA00000065338900171
Preparation process such as step (1)～(4), yield 77%.
1H-NMR(300MHz，CDCl 3)：δ7.56(1H，s)，7.45-7.30(10H，m)，5.15-4.94(4H，m)，4.54(1H，d，J＝10.2Hz)，4.16-4.06(3H，m)，3.96-3.90(4H，m)，3.60(1H，t，J＝9.0Hz)，3.52-3.42(5H，m)，2.58-2.51(3H，m)，2.43-2.29(3H，m)，1.25(3H，t，J＝7.2Hz).
13C-NMR(75MHz，CDCl 3)：δ163.69，155.42，152.94，150.30，149.32，137.94，136.04，128.75，128.51，128.35，128.02，127.61，127.41，126.44，119.11，111.81，79.82，76.43，75.65，74.34，74.12，72.48，71.13，61.75，61.62，61.34，53.87，43.47，14.72.
Embodiment 28 benzyl Bergeninum methyl-formiate based piperazine derivatives
Figure GSA00000065338900172
Preparation process such as step (1)～(4), yield 72%.
1H-NMR(300MHz，CDCl 3)：δ7.57(1H，s)，7.47-7.32(10H，m)，5.16-4.95(4H，m)，4.55(1H，d，J＝10.2Hz)，4.12(1H，m)，3.97-3.91(4H，m)，3.67(3H，s)，3.62(1H，t，J＝9.0Hz)，3.53-3.43(5H，m)，2.59-2.52(3H，m)，2.44-2.30(3H，m).
13C-NMR(75MHz，CDCl 3)：δ163.67，155.41，152.86，150.28，149.37，137.43，136.96，128.84，128.32，128.27，128.03，127.78，127.56，126.37，119.17，111.56，79.75，76.83，75.46，74.98，74.34，72.33，71.75，61.43，61.98，53.75，52.13，43.52.
Embodiment 29 Bergeninum imdazole derivatives
With corresponding benzyl Bergeninum imdazole derivatives implementation step (5), yield 65%.
1H-NMR(300MHz，DMSO-d6)：δ7.68(1H，s)，7.24(1H，s)，7.00(1H，s)，6.91(1H，s)，4.92(1H，d，J＝10.2Hz)，4.50(1H，d，J＝14.4Hz)，4.19-4.12(1H，dd，J 1＝14.4Hz，J 2＝14.7Hz)，3.86(1H，t，J＝9.6Hz)，3.76-3.63(4H，m)，3.04(1H，t，J＝9.3Hz).
13C-NMR(75MHz，DMSO-d6)：δ163.61，151.17，147.97，140.82，138.03，128.21，120.43，118.33，115.86，109.69，79.78，79.32，73.34，72.06，70.87，59.76，47.08.
Embodiment 30 Bergeninum glyoxal ethyline derivatives
Figure GSA00000065338900182
With corresponding benzyl Bergeninum glyoxal ethyline derivative implementation step (5), yield 50%.
1H-NMR(300MHz，DMSO-d6)：δ7.21(1H，s)，7.09(1H，s)，7.08(1H，s)，6.93(1H，s)，4.54(1H，d，J＝15.0Hz)，4.26-4.18(1H，dd，J 1＝15.0Hz，J 2＝15.0Hz)，3.99(1H，t，J＝9.9Hz)，3.87-3.80(5H，m)，3.34-3.30(2H，m)，2.46(3H，s).
13C-NMR(75MHz，DMSO-d6)：δ165.91，152.22，149.26，142.37，126.24，122.04，119.69，117.38，111.23，81.20，81.03，75.33，73.98，72.69，60.94，12.53.
Embodiment 31 Bergeninum 2-ethyl imidazol(e) derivatives
Figure GSA00000065338900191
With corresponding benzyl Bergeninum 2-ethyl imidazol(e) derivative implementation step (5), yield 50%.
1H-NMR(300MHz，CD 3OD)：δ7.31(1H，s)，7.15(1H，s)，6.98(1H，s)，4.78(1H，d，J＝10.5Hz)，4.53(1H，d，J＝15.3Hz)，4.11-4.02(2H，m)，3.93(3H，s)，3.88-3.80(2H，m)，3.40-3.34(2H，m)，2.79-2.72(2H，m)，1.32(3H，t，J＝7.5Hz).
13C-NMR(75MHz，CD 3OD)：δ164.50，150.79，150.04，147.48，140.84，127.27，119.81，117.82，115.04，110.65，80.27，79.64，74.11，73.41，71.24，60.71，47.05，19.84，11.97。
Embodiment 32 Bergeninums 4,5-methylimidazole derivative
Figure GSA00000065338900192
With corresponding benzyl Bergeninum methylimidazole derivative implementation step (5), yield 52%.
1H-NMR(300MHz，CDCl 3)：δ7.61(1H，s)，7.25(1H，s)，5.21-5.07(4H，m)，4.26-4.13(2H，m)，3.95-3.81(6H，m)，3.51(1H，d，J＝8.2Hz)，3.02(1H，t，J＝8.2Hz)，2.18(3H，s)，2.11(3H，s).
13C-NMR(75MHz，DMSO-d6)：δ163.63，151.16，147.98，140.80，138.05，128.34，120.44，118.33，115.85，109.63，79.72，79.31，73.34，72.06，70.80，59.46，47.18，13.25，10.54.
Embodiment 33 Bergeninum benzimidizole derivatives
Figure GSA00000065338900201
With corresponding benzyl Bergeninum benzimidizole derivatives implementation step (5), yield 70%.
1H-NMR(300MHz，DMSO-d6)：δ8.18(1H，s)，7.63(1H，t，J＝6.6Hz)，7.26-7.16(2H，m)，6.96(1H，s)，5.88(1H，s)，5.70(1H，s)，4.90(1H，d，J＝10.2Hz)，4.73(1H，d，J＝8.7Hz)，4.52-4.45(1H，dd，J 1＝15.0Hz，J 2＝14.7Hz)，3.85-3.69(6H，m)，3.14-3.02(1H，m).
13C-NMR(75MHz，DMSO-d6)：δ163.57，150.71，148.05，144.78，143.11，140.81，134.43，122.32，121.47，119.27，118.42，116.42，110.64，109.38，79.71，78.74，73.43，71.90，70.90，59.81，44.98.
Embodiment 34 Bergeninum methyl piperazine derivates
Figure GSA00000065338900202
With corresponding benzyl Bergeninum methyl piperazine derivate implementation step (5), yield 57%.
1H-NMR(300MHz，CD 3OD)：δ7.33(1H，s)，7.15(1H，s)，4.81(1H，d，J＝10.5Hz)，4.08(1H，t，J＝9.6Hz)，3.96(3H，s)，3.86(1H，t，J＝9.0Hz)，3.45-3.37(2H，m)，2.92-2.64(10H，m)，2.45(3H，s).
13C-NMR(75MHz，CD 3OD)：δ164.59，150.77，147.73，140.98，117.83，115.64，110.32，79.88，76.73，74.13，73.31，73.00，60.59，59.58，54.55，52.45，44.99.
Embodiment 35 Bergeninum ethyl piperazidine derivatives
Figure GSA00000065338900211
With corresponding benzyl Bergeninum ethyl piperazidine derivative implementation step (5), yield 55%.
1H-NMR(300MHz，CD 3OD)：δ7.35(1H，s)，7.13(1H，s)，4.82(1H，d，J＝10.5Hz)，4.09(1H，t，J＝9.6Hz)，3.98(3H，s)，3.85(1H，t，J＝9.0Hz)，3.44-3.38(2H，m)，2.91-2.62(10H，m)，2.66-2.02(12H，m)，1.06(3H，t，J＝7.2Hz).
13C-NMR(75MHz，CD 3OD)：δ164.57，150.74，147.55，140.64，117.33，115.24，110.72，79.34，76.53，74.13，73.31，73.02，60.56，59.55，54.52，52.44，52.24，11.91.
Embodiment 36 Bergeninum Phenylpiperazine derivatives
Figure GSA00000065338900212
With corresponding benzyl Bergeninum ethyl piperazidine derivative implementation step (5), yield 68%.
1H-NMR(300MHz，CDCl 3)：δ7.32(1H，s)，7.06(2H，dd，J 1＝8.4Hz，J 2＝8.0Hz)，6.65(1H，m)，6.62(2H，d，J＝8.4Hz)，5.18-4.95(4H，m)，4.55(1H，d，J＝10.4Hz)，4.08(1H，t，J＝9.9Hz)，3.91-3.86(4H，m)，3.60-3.46(2H，m)，2.65-2.26(10H，m).
13C-NMR(75MHz，CD 3OD)：δ164.69，150.37，149.62，147.71，140.96，129.66，118.35，117.81，115.61，114.26，110.55，79.84，76.00，74.32，73.32，73.03，60.56，59.48，54.58，52.42。
Embodiment 37 Bergeninum fluorophenyl bridged piperazine derivatives
Figure GSA00000065338900221
With corresponding benzyl Bergeninum fluorophenyl bridged piperazine derivatives implementation step (5), yield 95%.
1H-NMR(300MHz，CD 3OD)：δ7.26(1H，s)，7.01-6.88(4H，m)，4.78(1H，d，J＝10.5Hz)，4.05(1H，t，J＝9.3Hz)，3.90-3.69(7H，m)，3.43(1H，t，J＝9.0Hz)，3.08(4H，s)，2.90-2.84(1H，dd，J1＝13.5Hz，J2＝12.9Hz)，2.78-2.66(5H，m).
13C-NMR(75MHz，CD 3OD)：δ164.56，157.37，154.11，150.58，147.68，140.86，139.81，139.69，124.52，122.86，122.76，119.07，117.79，116.28，116.00，115.71，110.21，79.86，76.60，74.13，73.64，73.12，60.67，60.18，53.81，50.56.
Embodiment 38 Bergeninum dimethylamino-propyl bridged piperazine derivatives
Figure GSA00000065338900222
With corresponding benzyl Bergeninum dimethylamino-propyl bridged piperazine derivatives implementation step (5), yield 68%.
1H-NMR(300MHz，CD 3OD)：δ7.42(1H，s)，5.10-4.90(4H，m)，4.51(1H，d，J＝10.2Hz)，4.03(1H，d，J＝9.9Hz)，3.90-3.84(4H，m)，3.55-3.47(2H，m)，2.57-2.32(20H，m)，1.72-1.70(2H，m).
13C-NMR(75MHz，CD 3OD)：δ163.66，146.20，145.25，144.15，124.57，117.59，111.61，79.94，76.75，75.73，74.33，73.94，72.45，71.63，61.77，61.22，57.37，55.97，53.22，52.24，44.73，23.86.
Embodiment 39 Bergeninum hydroxyethyl propyl group bridged piperazine derivatives
Figure GSA00000065338900231
With corresponding benzyl Bergeninum hydroxyethyl propyl group bridged piperazine derivatives implementation step (5), yield 65%.
1H-NMR(300MHz，CD 3OD)：δ7.51(1H，s)，5.13-4.94(4H，m)，4.52(1H，d，J＝10.2Hz)，4.10(1H，t，J＝10.2Hz)，3.94-3.90(4H，m)，3.63-3.42(5H，m)，2.63-2.44(12H，m).
13C-NMR(75MHz，CD 3OD)：δ163.62，146.15，145.55，144.34，124.55，117.75，111.97，79.95，76.73，75.73，74.12，72.53，71.13，61.76，61.35，59.34，57.93，54.14，52.77。
Embodiment 40 Bergeninum ethyl formate based piperazine derivatives
Figure GSA00000065338900232
With corresponding benzyl Bergeninum ethyl formate based piperazine derivative implementation step (5), yield 70%.
1H-NMR(300MHz，CD 3OD)：δ7.52(1H，s)，5.14-4.93(4H，m)，4.51(1H，d，J＝10.2Hz)，4.13-4.03(3H，m)，3.92-3.88(4H，m)，3.58(1H，t，J＝9.0Hz)，3.50-3.40(5H，m)，2.55-2.49(3H，m)，2.41-2.27(3H，m)，1.26(3H，t，J＝7.2Hz).
13C-NMR(75MHz，CD 3OD)：δ163.24，155.79，146.16，145.34，144.67，124.45，117.78，111.92，79.89，76.40，75.60，74.64，74.29，72.48，71.24，61.52，61.64，61.37，53.87，43.47，14.78.
Embodiment 41 Bergeninum methyl-formiate based piperazine derivatives
Figure GSA00000065338900241
With corresponding benzyl Bergeninum methyl-formiate based piperazine derivative implementation step (5), yield 75%.
1H-NMR(300MHz，CD 3OD)：δ7.53(1H，s)，5.12-4.90(4H，m)，4.53(1H，d，J＝10.2Hz)，4.15(1H，m)，3.93-3.88(4H，m)，3.69(3H，s)，3.61(1H，t，J＝9.0Hz)，3.54-3.45(5H，m)，2.59-2.54(3H，m)，2.45-2.30(3H，m).
13C-NMR(75MHz，CD 3OD)：δ163.62，155.45，146.76，145.57，144.64，124.35，117.75，111.89，79.45，76.74，75.26，74.85，74.25，72.37，71.79，61.47，61.93，53.71，52.16，43.57。

Claims (2)

1. the Bergeninum analog derivative that has following general structural formula (I):
Figure FSA00000065338800011
(1) work as R=Bn, Me, during Et, R '=OH
(2) when R=Bn, R '=OTs, OMs, OTBS, I, Br, Cl,
NHBn，NHCH 2Ph(OCH 3)-4，NHCH 2Ph(I)-4，NHCH 2Ph(Br)-4，NHCH 2Ph(Cl)-4，
Figure FSA00000065338800012
(3) when R=OH,
Figure FSA00000065338800013
Figure FSA00000065338800014
2. the preparation method of a Bergeninum analog derivative as claimed in claim 1 is characterized in that step is as follows:
(1), the protection of Bergeninum phenolic hydroxyl group:
With the Bergeninum is raw material, adds halogenation benzyl or methyl halide or halo ethane and salt of wormwood, and the mole number ratio is 1/2～5/6～10, adds N, dinethylformamide, raw material is dissolved fully after, room temperature to 60 ℃ stirring reaction 24～72 hours; Evaporated under reduced pressure N behind the dinethylformamide, adds volume ratio and is 3/1 ethyl acetate and water, tell organic layer after, water layer is used ethyl acetate extraction 3～5 times again; Merge organic phase, be washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent obtains white powder solid product Bergeninum phenolic hydroxyl group protection thing;
(2), the reaction of Bergeninum alcoholic extract hydroxyl group:
With step (1) product is raw material, adds muriate and pyridine, tertiary amine or salt of wormwood, and the mole number ratio is 1/2～3/5～8, add after methylene dichloride dissolves raw material fully, in 0 ℃ to stirring at room reaction 24～72 hours; Behind evaporated under reduced pressure pyridine or the tertiary amine, add volume ratio and be 3/1 methylene dichloride and water, tell organic layer after, water layer is with dichloromethane extraction 3～5 times; Merge organic phase, be washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent gets crude product, behind silica gel column chromatography, obtains white powder solid product Bergeninum alcoholic extract hydroxyl group reactant;
(3), the halid preparation of Bergeninum:
With step (2) product is raw material, adds sodium halide or potassium halide, and the mole number ratio is 1/1～3, is solvent refluxing reaction 3～5 days with acetone; With the methylene dichloride dissolving, solids removed by filtration obtains crude product behind the filtrate evaporate to dryness, behind silica gel column chromatography, obtains white powder solid Bergeninum halogenide behind the evaporated under reduced pressure acetone;
(4), the preparation of Bergeninum derivative:
With step (2) product or step (3) product is raw material, adds amine or glyoxaline compound, and the mole number ratio is 1/1～5, and with N, dinethylformamide is a solvent, 90 ℃ of following back flow reaction 20～60 hours; Evaporated under reduced pressure N behind the dinethylformamide, adds volume ratio and is 3/1 methylene dichloride and water, tell organic layer after, water layer is with dichloromethane extraction 3～5 times; Merge organic phase, be washed to neutrality with saturated common salt, through the anhydrous sodium sulfate drying after-filtration, the evaporated under reduced pressure solvent gets crude product, behind silica gel column chromatography, obtains white powder solid Bergeninum derivative;
(5), Bergeninum derivative debenzylation:
With step (4) product is raw material, in the ratio adding palladium-carbon catalyst of raw materials quality 5～20%, is solvent with methyl alcohol, and 20～50 ℃ were reacted 20～60 hours under nitrogen atmosphere; Remove by filter palladium-carbon catalyst, the evaporated under reduced pressure solvent gets crude product, behind silica gel column chromatography, obtains white powder solid Bergeninum derivative debenzylation product.
CN 201010129152 2010-03-22 2010-03-22 Bergenin derivative and preparation method thereof Pending CN101812068A (en)

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CN102337308A (en) * 2011-10-12 2012-02-01 扬州大学 Method for converting bergenin into special nitrogenous derivative by using penicillium
CN103923093A (en) * 2014-04-15 2014-07-16 中国药科大学 Bergenin derivatives as well as preparation method and application thereof
CN104725393A (en) * 2015-02-02 2015-06-24 新乡医学院 Bergenin derivative as well as preparation method and application thereof
CN104873529A (en) * 2015-06-05 2015-09-02 泰山医学院 Antiviral drug composition containing nuciferine
CN106562957A (en) * 2015-10-08 2017-04-19 中国科学院微生物研究所 An application of a compound AJ-2 in preparation of a medicine treating or preventing influenza viruses
CN106632379A (en) * 2016-12-31 2017-05-10 陕西科技大学 Bergenin azacinnamate compound with anti-tumor activity and synthetic method thereof
CN108314689A (en) * 2018-05-03 2018-07-24 安阳工学院 4,11- diacyl bergenin derivative synthetic methods
CN108997379A (en) * 2018-06-22 2018-12-14 陕西科技大学 A kind of sulfur-bearing bergenin derivative and its synthetic method having antioxidant activity
CN110590800A (en) * 2019-10-11 2019-12-20 邹澄 7-p-benzoic acid azobergenin and preparation method and application thereof
CN113214262A (en) * 2020-02-05 2021-08-06 华创合成制药股份有限公司 Compound containing guanidyl and preparation method and application thereof
CN114456189A (en) * 2022-02-23 2022-05-10 安阳工学院 Bergenin sulfonate derivative and application thereof

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102337308A (en) * 2011-10-12 2012-02-01 扬州大学 Method for converting bergenin into special nitrogenous derivative by using penicillium
CN103923093A (en) * 2014-04-15 2014-07-16 中国药科大学 Bergenin derivatives as well as preparation method and application thereof
CN103923093B (en) * 2014-04-15 2016-08-17 中国药科大学 Bergeninum analog derivative and its preparation method and application
CN104725393A (en) * 2015-02-02 2015-06-24 新乡医学院 Bergenin derivative as well as preparation method and application thereof
CN104725393B (en) * 2015-02-02 2017-02-22 新乡医学院 Bergenin derivative as well as preparation method and application thereof
CN104873529A (en) * 2015-06-05 2015-09-02 泰山医学院 Antiviral drug composition containing nuciferine
CN106562957B (en) * 2015-10-08 2019-02-12 中国科学院微生物研究所 Application of the compound AJ-2 in the drug that preparation treats or prevents influenza virus
CN106562957A (en) * 2015-10-08 2017-04-19 中国科学院微生物研究所 An application of a compound AJ-2 in preparation of a medicine treating or preventing influenza viruses
CN106632379A (en) * 2016-12-31 2017-05-10 陕西科技大学 Bergenin azacinnamate compound with anti-tumor activity and synthetic method thereof
CN106632379B (en) * 2016-12-31 2019-06-04 西安泰科迈医药科技股份有限公司 A kind of Bergenin azepine cinnamate derivative compound and its synthetic method having anti-tumor activity
CN108314689A (en) * 2018-05-03 2018-07-24 安阳工学院 4,11- diacyl bergenin derivative synthetic methods
CN108314689B (en) * 2018-05-03 2021-03-26 安阳工学院 Synthesis method of 4, 11-diacyl bergenin derivative
CN108997379A (en) * 2018-06-22 2018-12-14 陕西科技大学 A kind of sulfur-bearing bergenin derivative and its synthetic method having antioxidant activity
CN108997379B (en) * 2018-06-22 2021-02-12 陕西科技大学 Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof
CN110590800A (en) * 2019-10-11 2019-12-20 邹澄 7-p-benzoic acid azobergenin and preparation method and application thereof
CN113214262A (en) * 2020-02-05 2021-08-06 华创合成制药股份有限公司 Compound containing guanidyl and preparation method and application thereof
CN114456189A (en) * 2022-02-23 2022-05-10 安阳工学院 Bergenin sulfonate derivative and application thereof

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