Application of atropurpuran derivative composition to medicines for increasing white blood cells
A technology for increasing white blood cells and compositions, which can be used in drug combinations, extracellular fluid diseases, active ingredients of heterocyclic compounds, etc., and can solve problems such as low safety and high toxicity of white blood cells
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Embodiment 1
[0010] The preparation of embodiment 1 compound Atropurpuran
[0011] The preparation method of compound Atropurpuran (I) refers to the literature published by Pei Tang et al. (Pei Tang et al., 2009.Atropurpuran, a novel diterpene with an unprecedented pentacycliccage skeleton, from Aconitum hemsleyanum var.atropurpureum.Tetrahedron Letters50(2009)460-462 )Methods.
[0012]
Embodiment 2
[0013] The synthesis of the O-bromoethyl derivative (II) of embodiment 2 Atropurpuran
[0014] Compound I (312 mg, 1.00 mmol) was dissolved in 10 mL of benzene, tetrabutylammonium bromide (TBAB) (0.08 g), 1,2-dibromoethane (3.760 g, 20.00 mmol) and 6 mL of 50% sodium hydroxide solution. The mixture was stirred at 35 °C for 6 h. After 6h, the reaction solution was poured into ice water, extracted twice with dichloromethane immediately, and the organic phase solutions were combined. Then the organic phase solution was washed with water and saturated brine three times successively, then dried with anhydrous sodium sulfate, and finally concentrated under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography (mobile phase: petroleum ether / acetone=100:1.0, v / v), the brown concentrated elution band was collected and the solvent was evaporated to obtain a yellow powder of Compound II (309mg, 74%) .
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Embodiment 3
[0019] The synthesis of O-(tetrahydropyrrolyl) ethyl derivative (III) of embodiment 3 Atropurpuran
[0020] Compound II (209 mg, 0.5 mmol) was dissolved in 18 mL of acetonitrile, anhydrous potassium carbonate (345 mg, 2.5 mmol), potassium iodide (84 mg, 0.5 mmol) and pyrrolidine (1420 mg, 20 mmol) were added thereto, and the mixture was heated to reflux for 2 h. After the reaction, the reaction solution was poured into ice water, extracted twice with an equal amount of dichloromethane, and the organic phases were combined. The combined organic phases were successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography (mobile phase: petroleum ether / acetone=100:1.0, v / v), and the concentrated brown elution band was collected and concentrated to give compound III as a brown solid (125 mg, 61%).
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