Asymmetric Synthesis of Tetrabenazine and Dihydrotetrabenazine
Asymmetric Synthesis of Tetrabenazine and Dihydrotetrabenazine
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DOI：
10.1021/jo900480n
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发表时间：
2009-05-15
影响因子：
3.6
通讯作者：
Johnson, Bruce F.
中科院分区：
文献类型：
--
作者：
Rishel, Michael J.;Amarasinghe, Kande K. D.;Johnson, Bruce F.
(+)-丁苯那嗪 (TBZ) 和 (+)-二氢丁苯那嗪 (DTBZ) 是治疗和分子成像应用中备受关注的药物，其对映选择性合成已完成，总产率为 21% (TBZ) 和 16% (DTBZ)，起始二氢异喹啉的 ee 大于 97%。该合成利用 Sodeoka 的钯催化不对称丙二酸酯加成来设定初始立构中心，然后进行一系列非对映选择性转化以合并剩余的不对称中心。
The enantioselective synthesis of (+)-tetrabenazine (TBZ) and (+)-dihydrotetrabenazine (DTBZ), agents of significant interest for therapeutic and molecular imaging applications, has been completed in 21% (TBZ) and 16% (DTBZ) overall yield and in > 97% ee from the starting dihydroisoquinoline. The synthesis utilizes Sodeoka's palladium-catalyzed asymmetric malonate addition to set the initial stereocenter followed by a number of diastereoselective transformations to incorporate the remaining asymmetric centers.