Enantioselective Total Synthesis of (–)-Siphonodictyal B and (+)-8-epi-Siphonodictyal B with Phosphatidylinositol 3-Kinase α (PI3Kα) Inhibitory Activity

Takuya Kikuchi, Koichi Narita, Ken Saijo, Chikashi Ishioka, Tadashi Katoh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The biologically interesting marine meroterpenoids (–)-siphonodictyal B and (+)-8-epi-siphonodictyal B were efficiently synthesized in 29–40 % overall yield in a longest linear sequence of 11 steps, starting from commercially available (+)-sclareolide. The synthesis involved the following crucial steps: (i) stereodivergent hydrogenation of a homoallylic decalin alcohol to install the requisite C8 stereogenic centre present in the decalin fragments; (ii) coupling of the decalin fragments with an aromatic moiety to assemble the desired carbon skeletons; and (iii) deprotection from multiple O-protective groups on the aromatic ring to complete the project synthesis. Both (–)-siphonodictyal B and (+)-8-epi-siphonodictyal B showed PI3Kα inhibitory activity, with potencies comparable to that of liphagal, a naturally occurring PI3Kα inhibitor. New structure–activity relationships for this class of marine meroterpenoids were also revealed.

Original languageEnglish
Pages (from-to)5659-5666
Number of pages8
JournalEuropean Journal of Organic Chemistry
Volume2016
Issue number34
DOIs
Publication statusPublished - 2016 Dec 1

Keywords

  • Biological activity
  • Natural products
  • Polyketides
  • Terpenoids
  • Total synthesis

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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