Development of a Concise Synthesis of (+)-lngenol.
The complex diterpenoid (+)-ingenol possesses a uniquely challenging scaffold and constitutes the core of a recently approved anti-cancer drug. This full account details the development of a short synthesis of 1 that takes place in two separate phases (cyclase and oxidase) as loosely modeled after t...
| Publicado en: | Journal of the American Chemical Society Vol. 136; no. 15; pp. 5799 - 5811 |
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| Autores principales: | , , , , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
4/16/2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=96121687&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 96121687 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 4/16/2014 vid: 136 iid: 15 pid: 997 pub: American Chemical Society artinfo: ui: 96121687 10.1021/ja501881p ppf: 5799 ppct: 12 formats: tig: atl: Development of a Concise Synthesis of (+)-lngenol. aug: au: McKerrall, Steven J. Jørgensen, Lars Kuttruff, Christian A. Ungeheuer, Felix Baran, Phil S. affil: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States su: Diterpenes Cyclases Density functional theory Pinacol rearrangement Pinacols sug: subj: Diterpenes Cyclases Density functional theory Pinacol rearrangement Pinacols ab: The complex diterpenoid (+)-ingenol possesses a uniquely challenging scaffold and constitutes the core of a recently approved anti-cancer drug. This full account details the development of a short synthesis of 1 that takes place in two separate phases (cyclase and oxidase) as loosely modeled after terpene biosynthesis. Initial model studies establishing the viability of a Pauson--Khand approach to building up the carbon framework are recounted. Extensive studies that led to the development of a 7-step cyclase phase to transform (+)-3-carene into a suitable tigliane-type core are also presented. A variety of competitive pinacol rearrangements and cyclization reactions were overcome to develop a 7-step oxidase phase producing (+)-ingenol. The pivotal pinacol rearrangement is further examined through DFT calculations, and implications for the biosynthesis of (+)-ingenol are discussed. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2014 holdings: @attributes: islocal: N |
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