{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:39:31Z","timestamp":1777599571870,"version":"3.51.4"},"reference-count":68,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T00:00:00Z","timestamp":1268697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2010,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Highly concise asymmetric total syntheses of (+)\u2010tetrabenazine (<jats:bold>1<\/jats:bold>), a drug for the treatment of chorea associated with Huntington\u2019s disease, and of (+)\u2010\u03b1\u2010dihydrotetrabenazine (<jats:bold>2<\/jats:bold>), an active metabolite of <jats:bold>1<\/jats:bold>, have been accomplished. Our synthetic route features a <jats:italic>trans<\/jats:italic>\u2010selective enol etherification, followed by an unprecedented cation\u2010dependent aza\u2010Claisen rearrangement to establish the carbon framework and two stereogenic centers of tetrabenazine. The syntheses consist of seven steps (34\u2009% overall yield) for (+)\u2010<jats:bold>2<\/jats:bold> and eight steps (22\u2009% overall yield) for (+)\u2010<jats:bold>1<\/jats:bold>.<\/jats:p>","DOI":"10.1002\/chem.200902591","type":"journal-article","created":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T15:25:38Z","timestamp":1268753138000},"page":"4623-4628","source":"Crossref","is-referenced-by-count":41,"title":["A Concise Total Synthesis of (+)\u2010Tetrabenazine and (+)\u2010\u03b1\u2010Dihydrotetrabenazine"],"prefix":"10.1002","volume":"16","author":[{"given":"Seung\u2010Mann","family":"Paek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam\u2010Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Kyung","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong\u2010Wha","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Jo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunyoung","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Ger","family":"Suh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,4,9]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"For recent reviews on HD see:"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201970"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_6_4_2","unstructured":"www.euro\u2010hd.net."},{"key":"e_1_2_6_5_2","unstructured":"\u00a0"},{"key":"e_1_2_6_6_2","unstructured":"www.fda.gov;"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2784"},{"key":"e_1_2_6_8_2","unstructured":"\u00a0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.6.1.7"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000198586.85250.13"},{"key":"e_1_2_6_11_2","unstructured":"\u00a0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.126.3272.507"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080478"},{"key":"e_1_2_6_14_2","unstructured":"\u00a0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(66)90031-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0026-895X(25)13112-X","volume":"33","author":"Scherman D.","year":"1988","journal-title":"Mol. 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K. M.","year":"1991"},{"key":"e_1_2_6_45_2","unstructured":"Olefin geometry was confirmed by1H 1H coupling constants. See ref.\u2005[15]."},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.54.3229"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol050578j"},{"key":"e_1_2_6_48_2","unstructured":"Bellus\u2013Claisen rearrangements in the presence of various metal cations and ligands have been reported by D.\u2005W.\u2005C. MacMillan\u2019s group. 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A mechanistic study is in progress."},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm950117b"},{"key":"e_1_2_6_63_2","unstructured":"Although the two enantiomers of racemic2were separated their optical rotations were not reported. However the optical rotation {[\u03b1]${{{20\\hfill \\atop {\\rm D}\\hfill}}}$=+55.6 (c=2 MeOH)} provided by Dr. G.\u2005A. Brine at the National Institute of Mental Health (NIMH) was close to the optical rotation of (+)\u20102synthesized by us {[\u03b1]${{{20\\hfill \\atop {\\rm D}\\hfill}}}$=+53.5 (c=1.60 MeOH)}."},{"key":"e_1_2_6_64_2","unstructured":"Two TBZ molecules were co\u2010crystallized and one TBZ molecule is shown. For details see the Supporting Information."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.200902591","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.200902591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:25:22Z","timestamp":1760293522000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.200902591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,9]]},"references-count":68,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2010,4,19]]}},"alternative-id":["10.1002\/chem.200902591"],"URL":"https:\/\/doi.org\/10.1002\/chem.200902591","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,9]]}}}