Preparation method and application of anti-leukemia selenonarcotine derivative
A technology of narcotin and derivatives, which is applied in the field of preparation of anti-leukemia selenonarcotin derivatives, can solve the problems of toxic side effects affecting the quality of life of leukemia patients, increasing drug resistance, and small toxic and side effects, reaching the natural content Abundant, low price, short synthetic route effect
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Embodiment 1
[0066] 1) Synthesis of Compound II:
[0067] Weigh 1.8g of narcotin hydrochloride and dissolve it in 50mL of concentrated hydrochloric acid, add 4g of paraformaldehyde in batches at room temperature, after the addition is complete, stir at 50°C for 2 hours. After the reaction, cool down, add ammonia dropwise to adjust the pH to 10, extract with dichloromethane (50mL×3), combine the organic phases, dry over anhydrous sodium sulfate, filter, and concentrate to obtain 1.9g of a colorless oily liquid with a yield of 98% . 1 H NMR (400MHz, CDCl 3 )δ6.91(d,J=8.3Hz,1H),6.14(d,J=8.2Hz,1H),5.88(s,2H),5.45(d,J=4.3Hz,1H),5.23(s, 1H), 4.56(s, 2H), 4.31(d, J=4.3Hz, 1H), 4.01(s, 3H), 3.92(s, 3H), 3.79(s, 3H), 2.70-2.54(m, 2H ), 2.46(s, 3H), 2.39-2.27(m, 1H), 1.90-1.86(m, 1H).
[0068] 2) Synthesis of compound III:
[0069] Dissolve 1.62g of compound II in 20mL of dichloromethane, and slowly add 0.5mL of thionyl chloride dropwise at 0°C. Methane was extracted three times, and the organ...
Embodiment 2
[0073] Synthesis of compound S2:
[0074]
[0075] Weigh 0.26g of compound IV into a reaction flask, add 5mL of anhydrous tetrahydrofuran and 0.14g of TMSCF at 0°C 3 , slowly add 0.1mL of tetrabutylammonium fluoride tetrahydrofuran solution (1mol / L) dropwise, and then transfer to room temperature to react for 2 hours. After the reaction is complete, add water to dilute, extract three times with ethyl acetate, and wash the organic phase with saturated brine. It was dried over anhydrous sodium sulfate, filtered and concentrated, and the resulting crude product was purified by silica gel column chromatography to obtain 0.20 g of the target product with a yield of 69%. 1 H NMR (400MHz, CDCl 3 )δ6.95(d, J=8.2Hz, 1H), 6.04(d, J=8.2Hz, 1H), 5.98(d, J=0.7Hz, 2H), 5.50(d, J=4.2Hz, 1H) ,4.39(d,J=4.3Hz,1H),4.27(d,J=11.6Hz,1H),4.12(d,J=11.6Hz,1H),4.09(s,3H),4.02(s,3H) , 3.86(s,3H),2.76–2.64(m,1H),2.53(s,3H),2.51–2.32(m,2H),1.88–1.73(m,1H).
Embodiment 3
[0077] Synthesis of Compound S3:
[0078]
[0079] Weigh 0.11g of compound IV and 0.015g of sodium borohydride into the reaction flask at the same time, add 1mL of absolute ethanol under nitrogen protection, stir at room temperature for 30 minutes, add 0.035g of methyl iodide, and continue the reaction at room temperature for 2 hours. After the reaction is complete, Dilute with water, extract three times with ethyl acetate, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, filter and concentrate, and the obtained crude product is purified by silica gel column chromatography (ethyl acetate:petroleum ether=1:3) , to obtain 0.071 g of the target product, yield 68%. 1 H NMR (400MHz, CDCl 3 )δ6.89(d,J=8.3Hz,1H),6.01(d,J=8.2Hz,1H),5.88(dd,J=7.3,1.3Hz,2H),5.46(d,J=4.2Hz, 1H), 4.34(d, J=4.2Hz, 1H), 4.02(s, 3H), 3.94(s, 3H), 3.79(s, 3H), 3.66–3.58 (m, 3H), 2.65–2.55(m , 1H), 2.47(s, 4H), 2.33–2.25(m, 1H), 1.97(s, 3H), 1.76 (ddd, J=13.5, 6.5, 3.1Hz, 1...
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