用猪去氧胆酸立体选择性合成脑甾醇的新方法  

Stereoselective synthesis of cerebrosterol from porcine hyodeoxycholic acid

作　　者：白晓杰[1] 吴四维[2] 周向东[1] 

机构地区：[1]第三军医大学药学院药物化学教研室,重庆400038 [2]重庆工商大学环境与生物工程学院应用化学系,重庆400067

出　　处：《第三军医大学学报》2016年第11期1313-1318,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(20072047)~~

摘　　要：目的探讨立体选择性合成脑甾醇的新方法。方法以猪去氧胆酸为原料,经甲酯化、还原、Wittig反应、Sharpless不对称双羟化等9步反应合成脑甾醇,其中以乙酰链甾醇为关键中间体,以Sharpless不对称双羟化反应为关键步骤。结果以52%的总收率、97%de的立体选择性合成脑甾醇,其结构用质谱(MS)、核磁共振氢谱(1HNMR)、核磁共振碳谱(13CNMR)、红外光谱(IR)和元素分析等证实。结论新的合成方法立体选择性高、收率高、每个中间体均为晶体易于重结晶纯化,可用于大量合成脑甾醇。Objective To establish a method to stereoselectively synthesize cerebrosterol. Methods The target molecule was synthesized through 9 steps including methyl esterification,reduction,Wittig reaction,Sharpless catalytic asymmetric dihydroxylation,etc.,with hyodeoxycholic acid as starting material,demosterol acetate as key intermediate,and Sharpless catalytic asymmetric dihydroxylation as key step.Results Cerebrosterol was synthesized with the total yield of 52% and stereoselectivity of 97% de,and it was identified by mass spectrometry（ MS）,proton magnetic resonance spectroscopy（1HNMR）,carbon magnetic resonance spectroscopy（13CNMR）,infrared spectroscopy（ IR）,elemental analysis,etc. Conclusion The synthesis of cerebrosterol is characterized by high yield,high stereoselctivity,easy recrystallization and purification of each intermediate,and feasible scalability.

关 键 词：脑甾醇 猪去氧胆酸 乙酰链甾醇 Sharpless不对称羟化反应 立体选择性 

分 类 号：R914.5[医药卫生—药物化学] R927[医药卫生—药学]