ISOLATION AND STEREOSTRUCTURES OF DOLASTATIN G AND NORDOLASTATIN G, CYTOTOXIC 35-MEMBERED CYCLODEPSIPEPTIDES FROM THE JAPANESE SEA HARE DOLABELLA AURICULARIA

摘要

A bioassay-directed fractionation of the cytotoxic constituents of the Japanese sea hare Dolabella auricularia resulted in the isolation of two 35-membered depsipeptides dolastatin G (1) and nordolastatin G (2), which showed cytotoxicity against HeLa S-3 cells with IC50 values of 1.0 and 5.3 mu g/mL, respectively. The gross structures of these substances were established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure of 1 was determined by chiral HPLC analysis of amino acid components obtained from acid hydrolysis of 1 and by the enantioselective syntheses of two degradation products arising from polyketide portions. Nordolastatin G (2) is a congener that has the same absolute stereochemistry as that of 1. [References: 14]