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

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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

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

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, 60(38), 8509-8527. https://doi.org/10.1016/j.tet.2004.06.125