齐墩果酸和去氧胆酸衍生物合成及抗血管生成活性研究  

Synthesis and antiangiogenic activity of oleanolic acid and deoxycholic acid derivatives

作　　者：王鹏龙[1] 程亚涛[1] 汪林[1] 徐士勋[1] 王艳慧[1] 李强[1] 雷海民[1] 

机构地区：[1]北京中医药大学中药学院中药化学系,北京100102

出　　处：《首都医科大学学报》2012年第4期494-497,共4页Journal of Capital Medical University

基　　金：国家重大新药创制(2009ZX09103-356)~~

摘　　要：目的合成齐墩果酸、去氧胆酸-丙酮基衍生物并评价2者对新生血管生成的影响。方法以丙酮/K2CO3作为反应体系,利用溴代川芎嗪分别与齐墩果酸和去氧胆酸发生亲核取代反应,得到齐墩果酸和去氧胆酸衍生物。采用鸡胚绒毛尿囊膜模型(chorioallantoic membrane,CAM)对其进行在体新生血管活性评价。结果产物结构经1H-NMR、13C-NMR及IR确证为齐墩果酸乙酰甲酯和和去氧胆酸乙酰甲酯;二者作用于CAM模型后,新生血管的数目均比空白组减少。结论在丙酮/K2CO3/溴代川芎嗪反应体系中,得到齐墩果酸和去氧胆酸-丙酮基衍生物;经CAM模型测试发现去氧胆酸-丙酮基衍生物对新生血管具有较好抑制活性。Two oleanolic acid and deoxycholic acid-acetonyl derivatives were synthesized; and the angiogenetic activities of the two compounds were aslo evaluated. Methods In the acetone/K2CO3 reaction system, TMP-Br took place nucleophilic substitution reaction with oleanolic acid and deoxycholie acid, respectively. And two novel oleanolie acid and deoxycholic acid-aeetonyl derivatives were obtained. The two compounds＇ angiogenic activity was evaluated on chick chorioallantoic membrane （CAM） model. Results The oleanolic acid and deoxyeholic acid-acetonyl derivatives＇ structure were confirmed by l H-NMR, 13 C-NMR and IR spectra. Both of the two compounds could suppress normal angiogenesis in CAM. Conclusion In the aeetone/K：CO3/TMP-Br reaction system, we got oleanolic acid and deoxyeholic acid-acetonyl derivatives, respectively. Moreover deoxycholic acid-acetonyl derivatives showed well anti-angiogenic activity on CAM assay.

关 键 词：齐墩果酸和去氧胆酸-丙酮基衍生物 鸡胚绒毛尿囊膜模型 抗血管生成活性 

分 类 号：R914.2[医药卫生—药物化学] R284.3[医药卫生—药学]