5 Total Synthesis of Marine Sesterterpenoid Dysidiolide

• Kajiwara Yasuhiro

  School of Pharmacy, Tokyo University of Pharmacy and Life Science

• Miyaoka Hiroaki

  School of Pharmacy, Tokyo University of Pharmacy and Life Science

• Yamada Yasuji

  School of Pharmacy, Tokyo University of Pharmacy and Life Science

Bibliographic Information

Other Title

• 5 海産セスタテルペノイドDysidiolideの全合成(口頭発表の部)

Abstract

Dysidiolide (1), a novel sesterterpenoid isolated from the Caribbean sponge Dysidia etheria de Laubenfels, exhibits inhibition of the protein phosphatase cdc25A. Dysidiolide possesses a unique carbon skeleton with structural features that find no precedent in nature. Thus its unique structure and biological activity prompted us to undertake the total synthesis of dysidiolide. Recently, the total synthesis of dysidiolide has been reported by three groups. Herein, we wish to report a novel total synthesis of dysidiolide using intramolecular Diels-Alder reaction as a key step. Cyclohexenone 2 was converted to α,β,γ,δ-unsaturated ketone 4 via enone 3. Conjugate addition of thiophenol to enone 4 and subsequent DIBAL-H reduction afforded alcohols 8a and 8b (8a:8b=1.6:1). Compound 8a was then converted to sulfoxidoester 10 by mCPBA oxidation and esterification with propiolic acid. Compound 10 was also derived from alcohol 8b by mCPBA oxidation and Mitsunobu reaction with propiolic acid. Sulfoxidoester 10 was refluxed in toluene to afford decalin 6 with elimination of sulfoxide and intramolecular Diels-Alder reaction. Decalin 6 was converted to lactone 13 having requisite four stereocenters at C-6, 7, 11 and 15 via 11 a and 12. Lactone 13 was reduced with DIBAL-H followed by LiBH_4 to give diol 14. Deoxyganation of compound 14 at C-12 and 24 gave alcohol 18 via 15, 16 and 17. Alcohol 18 was converted to iodide 19, followed by cross-coupling with isopropenyllithium in the presence of CuI and removal of THP group delivered alcohol 21. Alcohol 21 was oxidized with Dess-Martin periodinate to give aldehyde. Treatment of the aldehyde with 3-lithiofuran gave a mixture of alcohols 22a and 22b (22a:22b=1:1). After separation of the mixture, photochemical oxidation of 22a furnished (±)-dysidiolide.

Journal

• Symposium on the Chemistry of Natural Products, symposium papers

  Symposium on the Chemistry of Natural Products, symposium papers 41 (0), 25-30, 1999

  Symposium on the Chemistry of Natural Products Steering Committee

Details

• CRID: 1390282681056484736
• NII Article ID: 110006681800
• DOI: 10.24496/tennenyuki.41.0_25
• ISSN: 24331856
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed