PURPOSE: A stereoselective synthesis method of (+)-tetrabenazine is provided to ensure high efficiency and eco-friendly method and to synthesize (+)-tetrabenazine for treating Huntingtons chorea.CONSTITUTION: A stereoselective synthesis method of (+)-tetrabenazine of chemical formula 1 comprises a step of reacting 5-methyl-3-methylenehexan-2-one with 6,7-dimethoxy-3,4-dihydroisoquinoline through Mannich-Michael reaction under the presence of an asymmetric organic catalyst. The asymmetric organic catalyst is L-proline, proline amide, or (S)-TRIP &lsqb(S)-3,3-bis(2,4,6-triisopropylphenyl)-1,1-binaphthyl -2,2-diylhydrogen phosphate&rsqb. The reaction is performed in an organic solvent of DMSO(dimethylsulfoxide), dichloromethane, THF(tetrahydrofuran), chloroform, hexane, toluene, or dimethyl acetamide.COPYRIGHT KIPO 2013본 발명은 L-프롤린을 포함하는 비대칭성 유기촉매를 이용하여 마니히-마이클 반응을 진행시켜 입체선택적으로 (+)-테트라베나진을 합성하는 방법에 관한 것이다. 본 발명의 방법은 종래의 입체선택적 (+)-테트라베나진의 합성방법에 비해 고효율, 저비용 및 친환경적인 방법이다. 본 발명은 헌팅턴 무도병 등의 치료에 이용되는 (+)-테트라베나진의 새로운 입체선택적인 합성 방법을 제공한다.
