Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: Isolation, structure determination, synthesis, and biological activity

Kiyotake Suenaga, Tsuyoshi Mutou, Takunobu Shibata, Takashi Itoh, Tatsuya Fujita, Noboru Takada, Kozue Hayamizu, Masaki Takagi, Taiji Irifune, Hideo Kigoshi, Kiyoyuki Yamada

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide (1), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1. The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S 3 cells with an IC50 of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1. Graphical abstract.

Original languageEnglish
Pages (from-to)8509-8527
Number of pages19
JournalTetrahedron
Volume60
Issue number38
DOIs
Publication statusPublished - 2004 Sep 13
Externally publishedYes

Fingerprint

Depsipeptides
Hares
Cytotoxicity
Bioactivity
Oceans and Seas
Biological Assay
Inhibitory Concentration 50
Fatty Acids
High Pressure Liquid Chromatography
Pharmacology
Acids
Spectroscopic analysis
Bioassay
Fractionation
Nuclear magnetic resonance
Degradation
aurilide

Keywords

  • Aurilide
  • Cytotoxicity
  • Depsipeptide
  • Dolabella auricularia
  • Structure determination
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia : Isolation, structure determination, synthesis, and biological activity. / Suenaga, Kiyotake; Mutou, Tsuyoshi; Shibata, Takunobu; Itoh, Takashi; Fujita, Tatsuya; Takada, Noboru; Hayamizu, Kozue; Takagi, Masaki; Irifune, Taiji; Kigoshi, Hideo; Yamada, Kiyoyuki.

In: Tetrahedron, Vol. 60, No. 38, 13.09.2004, p. 8509-8527.

Research output: Contribution to journalArticle

Suenaga, K, Mutou, T, Shibata, T, Itoh, T, Fujita, T, Takada, N, Hayamizu, K, Takagi, M, Irifune, T, Kigoshi, H & Yamada, K 2004, 'Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: Isolation, structure determination, synthesis, and biological activity', Tetrahedron, vol. 60, no. 38, pp. 8509-8527. https://doi.org/10.1016/j.tet.2004.06.125
Suenaga, Kiyotake ; Mutou, Tsuyoshi ; Shibata, Takunobu ; Itoh, Takashi ; Fujita, Tatsuya ; Takada, Noboru ; Hayamizu, Kozue ; Takagi, Masaki ; Irifune, Taiji ; Kigoshi, Hideo ; Yamada, Kiyoyuki. / Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia : Isolation, structure determination, synthesis, and biological activity. In: Tetrahedron. 2004 ; Vol. 60, No. 38. pp. 8509-8527.
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