Oleanolic acid derivative as well as preparation method and application thereof
A technology of oleanolic acid and acetyloleanolic acid, applied in the directions of drug combination, pharmaceutical formulation, steroid, etc., can solve the problem that the anticancer activity is not significantly improved, the half-lethal concentration of cancer cells is low, and the damage is completely eliminated. The original structure of leanolic acid and other problems can inhibit the growth of tumor cell lines, improve anti-tumor activity, and be suitable for large-scale production.
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Embodiment 1
[0053] Embodiment 1 (the synthesis of oleanolic acid and diethylenetriamine reaction product OA-DETA that 3 hydroxyls are protected with acetyl group)
[0054] (1) Synthesis of oleanolic acid (3-O-acetyl oleanolic acid) protected by acetyl group at the 3-hydroxyl group:
[0055] Oleanolic acid (Mn=456.7, 4.57g) was dissolved in 19 mL of dry pyridine (pridine), and 9.45 mL of acetic anhydride was slowly added dropwise in an ice bath (0° C. ice bath) for a time of After 15 minutes, the ice bath was removed after the dropwise addition was completed, and the reaction was carried out at a room temperature of 25° C. for 5 hours. After the reaction was completed, the precipitate was filtered off, and the obtained filtrate was concentrated. Precipitate three times with water. Precipitate twice with methanol then, obtain white solid (4.061g, productive rate 81.4%), the proton nuclear magnetic resonance spectrum figure of the white solid that obtains is as follows figure 1 As shown,...
Embodiment 2
[0063] Embodiment 2 (the synthesis of oleanolic acid and ethylenediamine reaction product OA-EDA that 3 hydroxyls are protected with acetyl group)
[0064] (1) Synthesis of oleanolic acid (3-O-acetyl oleanolic acid) protected by acetyl group at the 3-hydroxyl group:
[0065] Step is with the synthetic step of 3-O-acetyl oleanolic acid in step (1) in embodiment 1;
[0066] (2) Synthesis of 3-O-acetyl oleanene-28-acid chloride:
[0067] The step is the same as the synthetic step of 3-O-acetyl oleanene-28-acyl chloride in step (2) in Example 2;
[0068] (3) Synthesis of OA-EDA, the bonded product of oleanolic acid and ethylenediamine, which is protected by an acetyl group at the 3-position hydroxyl group:
[0069] Dissolve the reaction product dissolved in step (2) in 15 mL of dry tetrahydrofuran and slowly add it dropwise into 3 mL of ethylenediamine for 15 minutes, react at room temperature 25°C for 24 hours, concentrate after the reaction, and then precipitate with water Th...
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