千金藤啶碱的全合成

Total synthesis of (±)-stepholidine

目的合成天然产物千金藤啶碱(SPD)。方法以3-羟基-4-苄氧基苯乙酸为原料,经内酯化、甲基化得到7-苄氧基-8-甲氧基苯并二氢异吡喃-3-酮(3),化合物3与3-甲氧基-4-苄氧基苯乙胺缩合得酰胺衍生物N-(4-苄氧基-3-甲氧基苯乙基)-2-(4-苄氧基-2-羟甲基-3-甲氧基苯基)乙酰胺(5),5经Bischler-Napieralski环合、硼氢化钠还原得2,10-二苄氧基-3,9-二甲氧基-5,8,13,13a-四氢-6H-二苯并[a,g]喹嗪(6),6经Raney-Ni催化氢化脱苄基得到千金藤啶碱。结果与结论该合成路线较短,操作简单,反应条件温和,成本较低,且在保证收率的前提下避免了高危险性的重氮甲烷的使用,目标化合物SPD及中间体的结构经核磁共振氢谱和质谱确证。

Aim To study and improve the total synthesis of （±）-stepholidine（SPD）.Methods 3-Hydroxy-4-benzyloxyphenylacetic acid was cyclized with formaldehyde and methylated to give compound 3,which was condensed with 3-methoxy-4-benzyloxyphenethylamine to obtain amide（5）.Compound 5 was subjected to Bischler-Napieralski cyclization followed by NaBH4 reduction giving tetrahydrobeberine（6）,which was hydrogenated with Raney-Ni to get SPD.Results and conclusion This method is short in steps and easy to control.And it avoids the use of dangerous diazomethane,the structure of target compound stepholidine and its intermediates were identified by 1H-NMR and MS.