Icaritin (ICT) derivative and preparation method and application thereof
A technology of icariin and derivatives is applied in the directions of pharmaceutical formulations, drug combinations, and medical preparations containing active ingredients, which can solve the problems of poor solubility and low oral bioavailability, and achieve high safety in clinical use. Effect
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Embodiment 1
[0035] The synthesis of embodiment 1 intermediate 1
[0036]
[0037] Dissolve 500mg (1.4mmol) of raw material icariin (ICT) in 20ml of acetone, add 188mg (1.4mmol) of potassium carbonate (1.4mmol) and 0.1ml (1.4mmol) of 2-bromoethanol, and reflux until the reaction is complete. Dry solvent, dissolve in ethyl acetate, and purify by column chromatography (dichloromethane: acetone = 40:1 and petroleum ether: ethyl acetate = 1:1 gradient elution), to obtain 378 mg of intermediate 1 as a yellow solid product, yield 61 %.
[0038] 1 H NMR (300MHz, CDCl 3 ):12.44(s,1H),8.13(d,J=9.00Hz,2H),7.08(d,J=9.06Hz,2H),6.43(s,1H),5.20(q,J=15.53Hz,1H ), 4.20(t, J=8.91Hz, 2H), 4.02(m, 4H), 3.93(s, 3H), 3.83(m, 2H), 3.56(d, J=6.72Hz, 2H), 1.82(s ,3H), 1.72(s,3H).
[0039] ESI-MS(m / z):479[M+Na] + .
Embodiment 2
[0040] The synthesis of embodiment 2 compound W-1
[0041]
[0042] Dissolve 500mg (1.4mmol) of raw material icariin (ICT) in 15ml of dichloromethane, add 270mg (1.4mmol) of BOC-valine, 240mg (1.5mmol) of carbodiimide (EDCI), 4- Dimethylaminopyridine (DMAP) 25 mg (0.2 mmol), stirred at room temperature for 1 h, until the reaction was complete, distilled under reduced pressure to dry the solvent, dissolved in ethyl acetate, purified by column chromatography (petroleum ether: ethyl acetate = 4:1), 654 mg of yellow solid product was obtained, and the yield was 85%.
[0043] The yellow solid product obtained above was dissolved in 10 ml of dichloromethane, and 139 mg (1.39 mmol) of concentrated hydrochloric acid was added under stirring conditions. After the dropwise addition was completed, it was stirred at room temperature for 20 min, and 700 mg of the yellow solid product W-1 was obtained by suction filtration, with a total yield of 81%.
[0044] 1 H NMR (300MHz, CDCl 3):...
Embodiment 3
[0046] The synthesis of embodiment 3 compound W-2
[0047]
[0048] Dissolve 500mg (1.4mmol) of raw material icariin (ICT) in 15ml of dichloromethane, add 265mg (1.4mmol) of BOC-alanine, 240mg (1.5mmol) of carbodiimide (EDCI), 4- Dimethylaminopyridine (DMAP) 25 mg (0.2 mmol), stirred at room temperature for 1 h, until the reaction was complete, distilled under reduced pressure to dry the solvent, dissolved in ethyl acetate, purified by column chromatography (petroleum ether: ethyl acetate = 4:1), 654 mg of yellow solid product was obtained, and the yield was 85%.
[0049] The yellow solid product obtained above was dissolved in 10 ml of dichloromethane, and 139 mg (1.39 mmol) of concentrated hydrochloric acid was added under stirring conditions. After the dropwise addition was completed, it was stirred at room temperature for 20 min, and 670 mg of the yellow solid product W-2 was obtained by suction filtration, with a total yield of 80%.
[0050] 1 H NMR (300MHz, CDCl 3 ...
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