外消旋加兰他敏全合成研究

Research on total synthesis of racemic galanthamine

针对加兰他敏全合成工艺中存在的问题,提出了一种全合成外消旋加兰他敏的新工艺.以异香草醛和酪胺为主要原料,经溴化、缩合还原、甲酰化、氧化偶合及还原五步反应,合成了外消旋加兰他敏.用高效液相色谱(HPLC)、红外光谱(IR)、质谱(MS)、核磁共振光谱(NMR)对产物及重要中间体进行定性及结构表征.分别考察了温度、催化剂、溶剂对单元反应过程的影响.结果表明,-60^-65℃下甲醇中溴化反应的收率为85.5%;以SSY型分子筛为催化剂、以NaBH4为还原剂的缩合还原反应的收率为91.2%;甲酰化反应的收率为80.0%;以K3[Fe(CN)6]为氧化剂,氧化偶合反应的收率为46.1%;以LiAlH4为还原剂的还原反应的收率为83.0%.

Considering the problem of total synthesis of galanthamine, a new technology of total synthesis of the racemic galanthamine was put forward. Using isovanillin and tyramine as the initial materials, racemic galanthamine was prepared in five steps including bromination, condensation and reduction, formylation, oxidation coupling and reduction. The title compound and the key intermediates were characterized by high performance liquid chromatography （HPLC）, infrared spectrum （IR）, mass spectrum （MS） and nuclear magnetic resonance （NMR）. The effects of temperature, catalyst and solvent on cell reaction were studied. The results show that Bromination in methanol has the yield of 85.5% at -60～ 65℃. The yield of condensation is 91.2% with SSY molecular sieve as catalyst and NaBH4 as reducing agent. The yield of formylation is 80.0%. The yield of oxidation phenolic coupling by K3[Fe（CN）6]is 46.1%. The yield of reduction is 83.0% with LiAlH4 as reducing agent.