阿江揽仁酸、贝萼皂苷元、常春藤酮酸及 4-异构常春藤酮酸的合成与糖原磷酸化酶抑制活性研究(英文)  

Synthesis and Biological Evaluation of Arjunolic Acid, Bayogenin, Hederagonic Acid and 4-Epi-hederagonic Acid as Glycogen Phosphorylase Inhibitors

作　　者：温小安[1] 柳军[2] 张陆勇[2] 倪沛洲[1] 孙宏斌[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学江苏药物筛选中心,南京210009

出　　处：《中国天然药物》2010年第6期441-448,共8页

基　　金：supported by the National Natural Science Foundation (Nos 30672523, 90713037 and 21002125);Specialized Research Fund for the Doctoral Program of Higher Education of China (No 2009121114452820);the program for New Century Excellent Talents in University (NCET-05-0495)~~

摘　　要：目的:探索含23-羟基或24-羟基的天然五环三萜化合物的糖原磷酸化酶抑制活性。方法:以齐墩果酸为起始原料分别合成阿江揽仁酸、贝萼皂苷元、常春藤酮酸及4-异构常春藤酮酸,并对其进行抗糖原磷酸化酶的生物活性评估。结果:以多步反应半合成了阿江揽仁酸、贝萼皂苷元、常春藤酮酸及4-异构常春藤酮酸,其中阿江揽仁酸的合成共11步,总收率约10%,贝萼皂苷元的合成其14步,总收率约12%。生物活性研究结果表明,阿江揽仁酸、贝萼皂苷元、常春藤酮酸及4-异构常春藤酮酸具有中等强度的糖原磷酸化酶抑制活性,其IC50介于53～103μmol·L?1之间。结论:阿江揽仁酸、贝萼皂苷元、常春藤酮酸及4-异构常春藤酮酸是中等强度的糖原磷酸化酶抑制剂,齐墩果烷骨架中23-羟基或24羟基的引入对GP抑制活性有不利影响的趋势。AIM： To study glycogen phosphorylase inhibitory activity of natural pentacyclic triterpenes bearing 23-hydroxy or 24-hydroxy. METHODS： Arjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid were synthesized from oleanolic acid as the starting material and biologically evaluated as glycogen phosphorylase inhibitors. RESULTS： Arjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid were successfully semi-synthesized by multiple steps. The synthesis of arjunolic acid was via 11 steps in about 10% overall yield, and bayogenin via 14 steps in about 12% overall yield. Biological evaluation indicated that arjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid showed moderate potency of glycogen phosphorylase inhibition with IC50 of 53-103 μmol·L？1. CONCLUSION： Arjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid are gly-cogen phosphorylase inhibitors with moderate potency. Insert of 23-hydroxy or 24-hydroxy to oleanane skeleton has a tendency to be unfavorable to GP inhibition.

关 键 词：天然五环三萜化合物 半合成 糖原磷酸化酶 

分 类 号：TQ460.31[化学工程—制药化工]