16.
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.
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