Dolabellin

D. auricularia from Japan contained dolabellin (199), a cytotoxic bis-thiazole. The structure was elucidated by spectral data examination and chemical degradation [200], D. auricularia also contained the cyclic hexapeptide dolastatin E (200) [201], the stereochemistry of which was determined by chemical degradation and total synthesis [202], A further cytotoxic hexapeptide, dolastatin I (201) was isolated from D. auricularia from Japan [203] and the stereostructure was confirmed by enantioselective synthesis [204], Dolastatin 18 (202) was isolated as a very minor cytotoxic component of D. auricularia from Papua New Guinea [205]. 

Dolabellin (169), a bisthiazole metabolite from the Japanese sea hare Dolabella auricularia containing 7,7-dichloro-octanoic acid, shows cytotoxicity against HeLa S3 cells (IC5o 6.1 pg/ml). The dechloro analogue has only one third of the toxicity [130]. 

Several other, more complex cysteine-derived polychlorinated peptide metabolites are known to arise in marine organisms. Dolabellin (968) was characterized from the Japanese sea hare Dolabella auricularia 1004). The absolute... 

Sone H, Kondo T, Kiryu M, Ishiwata H, Ojika M, Yamada K (1995) Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia Structural Determination and Synthesis. J Org Chem 60 4774... 

Figure 8 Structures of compounds 33 (aeruginosamide), 34 (dolabellin) and 35 (virenamide A).

Further Dolabella" compounds have now been isolated from collections of the marine cyanobacterium, Lyngbya majuscula. These include dolastatin 3 (S. S. Mitchell, D. J. Faulkner, K. Rubins and F. D. Bushman, J. Nat. Prod., 2(X)0, 63, 279) and lyngybyabellin A, a close analogue of dolabellin A (H. Luesch, W. Y. Yoshida, R. E. Moore, V. J. Paul and S. L. Mooberry, J. Nat. Prod., 2000, in press). 

Sone, H., Kondo, X, Kiryu, M., Ishiwata, H., Ojika, M., and Yamada, K. (1995). Dolabellin, a cytotoxic bisthiazole metabolite from the sea hare Dolabella auricularia Structural determination and synthesis. J. Org. Chem. 60, 4774-4781. 

Not to be confused with dolabellin, which is a bisthiazole metabolite isolated from the mollusk Dolabella auricularia. Figure 2036 Other examples of C5/C11 bicyclic diterpenes. 

Dolabellin is another example of a chlorine ester containing two thiazole rings (Sone et al., 1995) and aplysepine, a benzodiazepine that may be of fungal origin (Ojika, Yoshida, and Yamada, 1993b). 

Comprising two thiazole nuclei like dolabellin, hecto-chlorin and deacetylhectochlorin are macrolactones isolated from the Thai sea hare Bursatella leachii. The deacetylated form is strongly cytotoxic to several human cancerous lines, unlike hectochlorin (Suntomchashwej et al., 2005). 

Beware of possible confusion with dolabellin and neodolabeUine, which are diterpenes isolated from soft corals of the genus Clavularia (see Figure 20.56). 

---