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

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)5659-5666
ページ数8
ジャーナルEuropean Journal of Organic Chemistry
2016
34
DOI
出版ステータスPublished - 2016 12 1

ASJC Scopus subject areas

  • 物理化学および理論化学
  • 有機化学

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