(±)-瑞枯灵的合成

Synthesis of (±)-Reticuline

4-羟基-3-甲氧基苯乙胺和3-羟基-4-甲氧基苯乙酸经缩合、O-苄基保护得到2-(3-苄氧基-4-甲氧基苯基)-N-[2-(4-苄氧基-3-甲氧基苯基)乙基]乙酰胺,在POCl3作用下进行Bischler-Napieralski环合反应后,不经分离纯化直接与氯甲酸甲酯进行N-酰化得到7-苄氧基-1-(3-苄氧基-4-甲氧基苯亚甲基)-6-甲氧基-3,4-二氢-1H-异喹啉-2-羧酸甲酯,再经Pd-C氢化脱苄基和用四氢铝锂还原得到(±)-瑞枯灵,总收率23%。

Reticuline was synthesized from 4-hydroxy-3-methoxyphenylethylamine and 3-hydroxy- 4-methoxyphenylacetic acid by condensation and O-benzylation to give 2-(3-benzyloxy-4-methoxyphenyl)-N-[2-(4- benzyloxy-3-methoxyphenyl)ethyl]acetamide, which subjected to Bischler-Napieralski reaction with POCl3, N-acylation with methyl chloroformate to give 7-benzyloxy-1-(3-benzyloxy-4-methoxybenzylidene)-6-methoxy-3,4-dihydro-1H- isoquinoline-2-carboxylicacid methyl ester followed by deprotection and reduction with an overall yield of 23%.