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

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 stereo...

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Bibliographic Details
Published in:Tetrahedron 2004-09, Vol.60 (38), p.8509-8527
Main Authors: Suenaga, Kiyotake, Mutou, Tsuyoshi, Shibata, Takunobu, Itoh, Takashi, Fujita, Tatsuya, Takada, Noboru, Hayamizu, Kozue, Takagi, Masaki, Irifune, Taiji, Kigoshi, Hideo, Yamada, Kiyoyuki
Format: Article
Language:English
Subjects:
Aurilide
Cytotoxicity
Depsipeptide
Dolabella auricularia
Structure determination
Synthesis
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Summary: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 IC 50 of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1 . Graphical abstract
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2004.06.125