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Synthesis 2013; 45(23): 3251-3254
DOI: 10.1055/s-0033-1339900
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© Georg Thieme Verlag Stuttgart · New York

An Improved Synthesis of a Hydroxymethyl Tricyclic Ketone from Cyclohexanone, the Key Processes for the Synthesis of a Highly Potent Anti-inflammatory and Cytoprotective Agent

Akira Saito
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
,
Suqing Zheng
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
,
Motohiro Takahashi
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
,
Wei Li
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
,
Iwao Ojima
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
b   Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, USA   Fax: +1(631)6327942   Email: tadashi.honda@stonybrook.edu
,
Tadashi Honda*
a   Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York 11794, USA
b   Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, USA   Fax: +1(631)6327942   Email: tadashi.honda@stonybrook.edu
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Further Information

Publication History

Received: 16 June 2013

Accepted after revision: 11 September 2013

Publication Date:
23 September 2013 (online)

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Abstract

An improved synthesis of hydroxymethyl tricyclic ketone, (±)-(4aS,8aS)-8a-(hydroxymethyl)-1,1,4a-trimethyl-3,4,4a,6,7,8,8a,9,10,10a-decahydrophenanthren-2(1H)-one, in five steps (34% yield) from cyclohexanone has been successfully established. Accordingly, 10 grams of a highly potent anti-inflammatory and cytoprotective agent, (±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile (TBE-31), was obtained in 15 steps (9.2% overall yield) via the hydroxymethyl tricyclic ketone from 32 grams of cyclohexanone.

Key words

anti-inflammatory agents - antitumor agents - oxidation - reduction - reductive methylation - regioselectivity

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
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