A Concise Total Synthesis of (+)‐Tetrabenazine and (+)‐α‐Dihydrotetrabenazine |
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Authors: | Seung‐Mann Paek Dr. Nam‐Jung Kim Dongyun Shin Dr. Jae‐Kyung Jung Prof. Jong‐Wha Jung Dr. Dong‐Jo Chang Dr. Hyunyoung Moon Young‐Ger Suh Prof. |
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Affiliation: | 1. College of Pharmacy, Seoul National University, Seoul 151‐742 (Korea), Fax: (+82)?2‐888‐0649;2. Life Sciences Research Division, Korea Institute of Science and Technology, Seoul 130‐650 (Korea);3. College of Pharmacy, Chungbuk National University, Cheongju 361‐763 (Korea) |
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Abstract: | Highly concise asymmetric total syntheses of (+)‐tetrabenazine ( 1 ), a drug for the treatment of chorea associated with Huntington’s disease, and of (+)‐α‐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 . |
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Keywords: | bentazines Claisen rearrangement rearrangement total synthesis |
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