(R)-(+)-脱水芽子碱甲酯的合成工艺研究及结构表征  

Synthetic of(R)-(+)-anhydroecgonine methyl ester technology and their structure confirmation

作　　者：于江[1,2] 段玉清 魏会强[3] 李祎亮[3] 侯文彬[1,2] YU Jiang1,2, DUAN Yu-qing3, WEI Hui-qiang3, LI Yi-liang3, HOU Wen-bin1,2(1. Tianjin Medical University, Tianjin 300070, China 2. Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China 3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300193, Chin)

机构地区：[1]天津医科大学,天津300070 [2]天津药物研究院,天津300193 [3]中国医学科学院北京协和医学院放射医学研究所天津市放射医学与分子核医学重点实验室,天津300192

出　　处：《现代药物与临床》2018年第3期445-450,共6页Drugs & Clinic

基　　金：中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-022;2017-I2M-3-019)

摘　　要：目的对(R)-(+)-脱水芽子碱甲酯的合成工艺进行研究和结构表征。方法以托品酮为原料,经克莱森缩合、拆分、还原和消除得到目标产物,并以成盐的方式得到其富马酸盐,以溶剂挥发法培养单晶,采用X射线单晶衍射对结晶形态进行表征。结果优化了合成工艺,总收率为36%。测试结果表明不对称单位化学计量式为C_(14)H_(19)NO_6,相对分子质量为297.30,晶体密度为1.359 g/cm^3,该晶胞属于正交晶系,空间群为P2_12_12_1。结论本合成工艺简化了实验操作,更适合大规模制备,且为脱水芽子碱的结构确证提供了新的依据。Objective To study the synthetic technology and accurate structure of（R）-（＋）-Anhydroecgonine methyl ester.Methods Tropinone was used as starting materials to synthesize the target compound by a series of chemical reactions including Claisen condensation,resolution,reduction,and elimination.Evaporation method was used to grow single crystals of（R）-（＋）-Anhydroecgonine methyl ester fumarate,which were then characterized using single crystal X-ray diffraction.Results The synthetic technology was optimized with the yield of 36%.Results showed that the unit stoichiometric of the single crystals was C（14）H（19）NO6,and the relative molecular mass was 297.30,and crystal density was 1.359 g/cm^3.The unit cell belonged to an orthorhombic system,and the space group was P212121.Conclusion The synthetic technology simplifys the reaction procedure,and is more suitable for large-scaled preparation,which provides a new evidence for the structure confirmation of（R）-（＋）-Anhydroecgonine methyl ester.

关 键 词：(R)-(+)-脱水芽子碱甲酯 帕金森病 多巴胺转运蛋白 显像剂 单晶 

分 类 号：R914.2[医药卫生—药物化学]