Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity |
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Authors: | Kiyotake Suenaga Tsuyoshi Mutou Takashi Itoh Noboru Takada Masaki Takagi Hideo Kigoshi Kiyoyuki Yamada |
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Affiliation: | a Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan b Department of Chemistry, University of Tsukuba, 1-1-1 Tennoudi, Tsukuba, Ibaraki 305-8571, Japan |
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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 S3 cells with an IC50 of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1. |
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Keywords: | Aurilide Dolabella auricularia Depsipeptide Cytotoxicity Structure determination Synthesis |
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