Study On Extraction Of Betulin And Synthesis Of Betulin Derivatives

In the past tens years, malignant tumor and AIDS are becoming the most serious diseases to human. Currently, camptothecin, paclitaxel and their derivatives are used as anti-tumor drugs, Zidovudine and delavirdine is used to treat HIV. All these drugs have toxic side effects and drug resistance. The development of anti-tumor and anti-HIV drugs with high efficiency and low toxicity has been a research hotspot in this field.Betulinic acid is a nature product isolated from several genus of higher plants. Recently, betulinic acid has been demonstrated to possess a remarkably selective antitumor activity against human melanoma and an anti-HIV activity in H9 lymphocytic dells. For an extensive biological efficacy study, a large amount of betulinic acid was needed.The bark of white birch contains betulin (25%) and betulinic acid (0.025%). Betulin extracted from bark of birch was purified by several kinds of mix solvents. The betulinic acid and its derivatives can be provided from betulin through a simple synthetic approach. Here we report extraction of betulin from the bark of white birch and a concise step conversion of betulin to betulinic acid, along with a synthetic study.The results showed that the optimal experimental conditions were as follows:the white birch bark was extracted with methanol for 7h and the ratio of the bark to the extraction solvent was 1/15. And the crude betulin was recrystallized from isopropanol/ methanol (10/1, v/v). The solid liquid ratio is 1/40. The yield of betulin is 18.5% with the purity of 98.20%.Betulinic acid has been synthesized from betulin with two different routes. The first route, betulinic acid was synthesized by oxidizing betulin with Jones reagent, followed by selective reduction with NaBH4. The reaction condition was optimized. An efficient method to purify the betulonic acid has been established. A new method to synthesize betulinic acid has been developed. For this route, betulin was changed into betulinaldehyde with aluminium isopropoxide/acetone as oxidant at first, and then the betulinaldehyde was converted to betulinic acid with Ag2O/KOH.Several betulin derivatives have been synthesized and their inhibition effects on human HePG2 cells and MCF7 cells were assessed by MTT. The result shows that the betulonic acid has better inhibition on MCF7 cells than on HePG2 cells.