Studies On Chemical Modification Of Boswellic Acids And Their Anti-Tumor Activity

Hunting for high-efficiency, low-toxic anti-tumor agents is one of hot topics in new drugs research. Extracting anti-tumor agents from traditional Chinese medicine, designing and synthesizing anti-tumor drugs based on the structures of natural products are not only the major part of traditional Chinese medicine modernization but also the important direction of anti-tumor drugs research.Boswellia serrata is extensively applied as one kind of herbs. Recently, the anti-tumor mechanism of boswellic acids were investigated, which indicated that this kind of compounds are potent apoptosis inducers, and expected to become the preferred anti-tumor agents.In this thesis, taking boswellic acids extracted from Bowellia carterria and Boswellia serrata as leading compound, through the modification on position 3 and position 24 of the structure, total 42 boswellic acids analogues out of six series were designed and synthesized. These structures include: 3-acetyl(or 3-hydroxy)-11-oxo-β-boswellic acid esters (â… ₁～ â… ₇), 3-alkanoyl-11-oxo-β-boswellic acid esters (â…¡₁～ â…¡₇), 3-alkyl-11-oxo-β-boswellic acid esters (â…¢₁～Ⅲ₈), 3,11-dioxo-β-boswellic acid esters (â…£₁～Ⅳ₄), 3-(N-alkanoyloxyimino)-11-oxo-β-boswellic acid esters (â…¤₁～Ⅴ₈), 3-(N-alkoxyimino)-11-oxo-β-boswellic acid esters (â…¥₁～Ⅵ₈). 41 compounds of which are new compounds that have never been reported in literatures. The structures of these compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR and MS.Through the modification of reaction conditions, the chlorination and esterification of 24-carboxyl group as well as the hydrolyzation of 3- acetoxy of AKBA were successfully combined into one pot reaction, thereby simplified the subsequent procedure. The total yield of the three steps was 60.5～71.5%. After the investigating on the oxidization reaction conditions of 3-hydroxyl group it was found that the ester form of 24-carboxyl group is essential to the oxidation reaction of position 3. For compounds possessing two...