光学纯丁苯那嗪的不对称合成尝试

Attempted asymmetric synthesis of optically pure tetrabenazine

摘要: 参照文献方法，以3，4-二甲氧基苯乙胺为原料，首先合成重要中间体6，7-二甲氧基-1，2，3，4-四氢异喹啉-1-乙酸甲酯，经Mannich反应、Dieckmann缩合和水解脱羧合成外消旋丁苯那嗪，并对路线进行了优化，使合成工艺更经济、便捷。并尝试通过拆分方法先确定11b位的构型，再诱导3位构型从而实现光学纯丁苯那嗪的手性合成。但因光学纯丁苯那嗪在酸性条件下会发生消旋化，所以未能实现光学纯丁苯那嗪的手性合成。

Abstract: Tetrabenazine was synthesized following modified literature method which would be more economical and convenient. On the other hand，methyl 2-(6，7-dimethoxy-1，2，3，4-tetrahydroisoquinolin-1-yl) acetate was resolved to provide the corresponding enantiomer with R configuration which was used as an intermediate for asymmetric synthesis of (3R-，11bR)-tetrabenazine. However，the attempted asymmetric synthesis of (3R，11bR)-tetrabenazine failed since racemization took place under acidic conditions in the last step.