新型LXRs配体——环氧胆烷酸甲酯一类物的化学合成

Chemical synthesis of methyl epoxycholanate analogues: novel ligands for liver X receptors

目的 合成两个新设计的具有环氧胆烷酸甲酯结构的化合物 :3β 羟基 5α ,6α 环氧胆烷酸甲酯、3β 羟基 5 β ,6 β 环氧胆烷酸甲酯 ,以期从中发现新的LXRs亚型选择性配体。方法 用我国丰富的甾体资源———猪去氧胆酸为原料 ,分别经三步和四步化学反应合成。结果 以 76 %和 42 %的总收率合成了两个目标化合物 ,并经波谱分析证实。结论 用高立体选择性高收率地成功合成了目标化合物。为研制治疗动脉粥样硬化等心脑血管疾病的新药打下了基础。

s: Objective To synthesize two compounds with epoxycholanate structure: methyl 3β hydroxy 5β, 6β epoxycholanate and methyl 3β hydroxy 5β, 6β epoxycholanate for getting new ligands of liver X receptors (LXRs). Methods The compounds were synthesized from hyodeoxycholic acid in 3 and 4 steps and analyzed with spectroscopy. Results The compounds were synthesized in total yields of 76% and 43%, respectively, and confirmted with spectroscopy. Conclusion The compounds are synthesized with epoxycholanate structure stereocontrolledly and successfully, which founds a basis for new drug synthesis in the treatment of cardiovascular diseases, like atherosclerosis etc.