Total Synthesis and Structure-activity Relationship of a Cytotoxic Polycyclic Ether Gymnocin-A

• Tsukano Chihiro

  東北大学大学院生命科学研究科分子生命科学専攻

• Sasaki Makoto

  Graduate School of Life Sciences, Tohoku University

Bibliographic Information

Other Title

• 細胞毒性ポリエーテルＧｙｍｎｏｃｉｎ‐Ａの全合成と構造活性相関
• サイボウ ドクセイ ポリエーテル Gymnocin A ノ ゼンゴウセイ ト コウゾウ カッセイ ソウカン

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.

Journal

• Journal of Synthetic Organic Chemistry, Japan

  Journal of Synthetic Organic Chemistry, Japan 64 (8), 808-818, 2006

  The Society of Synthetic Organic Chemistry, Japan

Keywords

• gymnocin-A
• polycyclic ether
• cytotoxicity
• total synthesis
• Suzuki-Miyaura coupling reaction
• structure-activity relationship

Details

• CRID: 1390282680289594624
• NII Article ID: 10017652125
• NII Book ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.64.808
• ISSN: 18836526
• ISSN: 00379980
• NDL BIB ID: 8060021
• Web Site: http://id.ndl.go.jp/bib/8060021
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8060021
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed