Tetrandrine derivatives and their preparation methods and their application in the preparation of antitumor drugs
An anti-tumor drug, tetrandrine technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problem of low cure rate and achieve the effect of simple preparation method, high product purity, and reduced toxicity
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Embodiment 1
[0036] Weigh 6.06g of bisbenzylisoquinoline (in general formula II, X=H), 12.50g of sodium 2-chloroacetate and 0.40g of sodium hydroxide, add them to a 500mL three-necked flask, dissolve in 100mL of propanol, heat and stir, Stir and react at 83°C for 8 hours, evaporate the solvent under reduced pressure, cool down to room temperature, neutralize to neutral with 10% HCl, add 50 mL of water and extract 3 times with ethyl acetate (50 mL×3), and use anhydrous Na 2 SO 4 Dry for 8 hours, recover ethyl acetate, trace the reaction and product separation and purification by TLC, and dry the solid at 60°C for 2 hours to obtain 6.21 g of a light brown powder product with a yield of 85.69% and a purity of 98.55% (HPLC). The melting point of the target product: 178-179°C, time-of-flight mass spectrum: M / e (355.1601), and the molecular formula is C 41 h 44 o 9 N 2 , 13 CNMR (75MHz, DMSO-d 6 ): δ20.63(C-4), 23.22(C-4’), 35.65(C-15), 49.67(C-15’), 50.67(NCH 3 ),53.22 (N'CH 3 ), 53.50 ...
Embodiment 2
[0038] Weigh 6.22g of 7-hydroxybisbenzylisoquinoline (in general formula II, X=OH), 10.00g of sodium 2-bromoacetate and 0.60g of potassium hydroxide, dissolve it in 100mL of n-butanol, and add it to a 500mL three-necked flask , heated and stirred to 118°C, and stirred at constant temperature for 6h, the solvent was evaporated under reduced pressure, cooled to room temperature, 3%H 2 SO 4 Neutralize to neutral, add 50mL of water and extract 3 times with chloroform (60mL×3), extract with anhydrous Na 2 SO 4 Dry for 8 hours, recover chloroform, trace the reaction and product separation and purification by TLC, and dry the solid at 60°C for 2 hours to obtain 6.52 g of a light red powder product with a yield of 88.03% and a purity of 97.36% (HPLC). The melting point of the target product: 181-182°C, time-of-flight mass spectrum: M / e (363.1575), and the molecular formula is C 41 h 44 o 10 N 2 , 13 According to CNMR, the main difference from Example 1 is 129.20 (C-7), which is...
Embodiment 3
[0040] Weigh 6.40g of 7-chlorobisbenzylisoquinoline (in general formula II, X=Cl), 5.50g of sodium 2-iodoacetate, γ-Al 2 o 3 - Add 2.60g of Na base to a 500mL three-neck flask, add 200mL of water and stir to mix, cool to 10°C, and react at a constant temperature for 48h, rise to room temperature and filter, neutralize the filtrate with dilute ammonia water to neutral, distill out water to liquid volume under reduced pressure About 40mL, crystallized overnight at 5°C, filtered, followed by TLC to track the reaction and separation and purification of the product, and the obtained solid was dried at 60°C for 4 hours to obtain 3.63g of a light red powder product with a yield of 47.85% and a purity of 98.15% (HPLC). The melting point of the target product: 176-178°C, time-of-flight mass spectrum: M / e (372.1406), and the molecular formula is C 41 h 43 o 9 N 2 Cl, 13 According to CNMR, the main difference from Example 1 is 105.45 (C-7), which is compound 3 in Table 1.
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