Formal synthesis of optically active ingenol via ring-closing olefin metathesis

Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, Hideo Kigoshi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo[4.4.1]undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.

Original languageEnglish
Pages (from-to)7802-7808
Number of pages7
JournalJournal of Organic Chemistry
Volume69
Issue number23
DOIs
Publication statusPublished - 2004 Nov 12
Externally publishedYes

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Alkenes
Diterpenes
Cyclization
Ketones
Aldehydes
Chlorides
Esters
Carbon
ingenol

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Formal synthesis of optically active ingenol via ring-closing olefin metathesis. / Watanabe, Kazushi; Suzuki, Yuto; Aoki, Kenta; Sakakura, Akira; Suenaga, Kiyotake; Kigoshi, Hideo.

In: Journal of Organic Chemistry, Vol. 69, No. 23, 12.11.2004, p. 7802-7808.

Research output: Contribution to journalArticle

Watanabe, K, Suzuki, Y, Aoki, K, Sakakura, A, Suenaga, K & Kigoshi, H 2004, 'Formal synthesis of optically active ingenol via ring-closing olefin metathesis', Journal of Organic Chemistry, vol. 69, no. 23, pp. 7802-7808. https://doi.org/10.1021/jo048833l
Watanabe, Kazushi ; Suzuki, Yuto ; Aoki, Kenta ; Sakakura, Akira ; Suenaga, Kiyotake ; Kigoshi, Hideo. / Formal synthesis of optically active ingenol via ring-closing olefin metathesis. In: Journal of Organic Chemistry. 2004 ; Vol. 69, No. 23. pp. 7802-7808.
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