Total synthesis and structure - Activity relationship of a cytotoxic polycyclic ether gymnocin - A

Chihiro Tsukano, Makoto Sasaki

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Gymnocin-A is a polycyclic ether toxin, isolated from the notorious red tide dinoflagellate, Karenia mikimotoi. Structurally, it is characterized by 14 contiguous and saturated ether rings and a 2-methyl-2-butenal side chain. The toxin is a rare polycyclic ether natural product that exhibits cytotoxicity against P 388 murine leukemia (IC50 = 1.3 μg/mL); however, the biological mechanism of action remains unknown to date. We have accomplished a highly convergent and efficient total synthesis of gymnocin-A by using our developed B-alkyl Suzuki-Miyaura coupling-based methodology. The convergent nature of our synthesis is well suited for preparation of various structural analogues of gymnocin-A to explore the structure-activity relationship (SAR). The results of SAR studies indicated that an α,β-unsaturated aldehyde functionality of the side chain and the molecular length of the polycyclic ether skeleton were the crucial structural elements required for cytotoxicity.

Original languageEnglish
Pages (from-to)808-818
Number of pages11
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume64
Issue number8
DOIs
Publication statusPublished - 2006 Aug

Keywords

  • Cytotoxicity
  • Gymnocin-A
  • Polycyclic etner
  • Structure-activity relationship
  • Suzuki-Miyaura coupling reaction
  • Total synthesis

ASJC Scopus subject areas

  • Organic Chemistry

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