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 (), a 26-membered cyclodepsipeptide. The gross structure of was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of . The cytotoxicity of 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 have been carried out by using synthetic .