Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia: Structural Determination and Synthesis

Article abstract of DOI:10.1021/jo00120a021

Dolabellin (1), a novel cytotoxic metabolite which consists of two thiazole hydroxy acids and a new dichlorinated β-hydroxy acid, was isolated from the Japanese sea hare Dolabella auricularia.The gross structure of 1 was elucidated on the basis of spectral data in conjunction with chemical degradation, which provided three methyl esters: methyl 2-(1-hydroxy-2-methylpropyl)thiazole-4-carboxylate (2), methyl 2-(1,2-dihydroxyethyl)thiazole-4-carboxylate (3), and methyl 7,7-dichloro-3-hydroxy-2-methyloctanoate (4).The absolute stereochemistry of 1 was determined by stereoselective syntheses of two degradation products 2 and 3 and two diastereomeric octanoates 7a,b (the dechloro derivatives of degradation product 4), and the enantioselective total synthesis of dolabellin itself.Dechlorodolabellin (23) was also synthesized.