A Concise Total Synthesis of (+)-Tetrabenazine and (+)-α-Dihydrotetrabenazine

被引：34

作者：

Paek, Seung-Mann ^{[1
]}

Kim, Nam-Jung ^{[1
]}

Shin, Dongyun ^{[2
]}

Jung, Jae-Kyung ^{[3
]}

Jung, Jong-Wha ^{[1
]}

Chang, Dong-Jo ^{[1
]}

Moon, Hyunyoung ^{[1
]}

Suh, Young-Ger ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea

[2] Korea Inst Sci & Technol, Life Sci Res Div, Seoul 130650, South Korea

[3] Chungbuk Natl Univ, Coll Pharm, Cheongju 361763, South Korea

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2010年 / 16卷 / 15期

关键词：

bentazines; Claisen rearrangement; rearrangement; total synthesis; STEREOCONTROLLED TOTAL-SYNTHESIS; AZA-CLAISEN REARRANGEMENT; ASYMMETRIC-SYNTHESIS; ACYL-CLAISEN; ENOL ETHERS; TETRABENAZINE; EFFICIENT; LACTAMS; BINDING; DRUG;

D O I：

10.1002/chem.200902591

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Highly concise asymmetric total syntheses of (+)-tetrabenazine (1), a drug for the treatment of chorea associated with Huntington's disease, and of (+)-alpha-dihydrotetrabenazine (2), an active metabolite of 1, have been accomplished. Our synthetic route features a trans-selective enol etherification, followed by an unprecedented cation-dependent aza-Claisen rearrangement to establish the carbon framework and two stereogenic centers of tetrabenazine. The syntheses consist of seven steps (34% overall yield) for (+)-2 and eight steps (22% overall yield) for (+)-1.

引用

页码：4623 / 4628

页数：6

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