Research On The Synthesis And Cvtotoxicitv Of Triazole Triterpenoids Derived From Betulin And Betulinic Acid, The Rearrangement Of Amides Of Betulinic Acid

Betulin, betulinic acid and their derived compounds are important pentacyclic lupane-type triterpenoids, exist widely in many plants. They have been studied in the last decades for their diversified pharmacological activities like anti-HIV, anticancer, anti-virus, anti-inflammatory, antioxide, etc. Because of poor solubility and bioavilability of betulin and betulinic acid, thus, reasearch on chemical modification of betulin and betulinic acid is significant meaningful. In this paper, we have studied the the purification method of betulinic acid, chemical modification of betulin and betulinic acid, and the cytotoxic test is also involved. The main work of this thesis is as follows:1. We have reviewed the progress made on the synthesis of novel structural triterpenoids with excellent chemical or biological activities that have appeared in the last years.2. We have developed a simple, highly effective method to separate betulinic acid from the wasters of betulin extraction procedures. From the fitted curves of solubilities of betulinic acid in different solvent systems, we obtained the best tecrystallization solvent, high purity of betulinic acid(>98%) was obtained in this study.3. In this thesis, we designed and synthesized a series of C-30-1,2,3-triazole derivatives from betulin and betulinic acid via click reaction in one pot. The structures were confirmed by NMR spectra. The cytotoxic experiment showed that the most of betulinic acid derived triazoles have higher cytotoxic profile than betulinic acid. Among of them compound30-[4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl] betulinic acid (3-lb) showed the best IC50value (1.3μm) against leukemia cell line HL-60(9fold higher potency than betulinic acid). Therefore, modification at C-30position of betulinic acid via click chemistry as cancer cells inhibitors might be able to provide a new strategy for the pharmacological screening of new therapeutic agents for treating cancers or other diseases.4. We studied the rearrangement of3-acetyl-C-28-amides of betulinic acid derivatives. Our research showed that C-28-amides of betulinic acid derivatives were quantitative converted to28-imineallobetulin derivatives in10%TFA-DCE solution at80℃. These28-imineallobetulin derivatives have not been reported before. This process represented a quantitative conversion of C-28primary amides of betulinic acid to rearrangement products with a broad substrate scope. The mechanism of this rearrangement reaction was also discussed in the text. The structure was confirmed by NMR and single crystal X-ray analysis. This rearrangement reaction would provide a new strategy for the reasearch of triterpenoid derivants.