THE STRUCTURES AND CYTOTOXIC PROPERTIES OF POLYKETIDE PEROXIDES FROM A PLAKORTIS SPONGE

A morphologically distinct Fijian sponge, Plakortis sp., has yielded t wo new peroxides, plakortolide E [5] and plakoric acid [12]. After sta nding for approximately one year, plakortolide E rearranged to plakort olide ether [10]. The structures of plakortolide E [5] and plakortolid e ether [10] were established from 2D nmr data and by analogy to a kno wn compound, plakortolide [3]. The stereochemistry of the bicyclic rin g substituents of 5 was established using nOe and NOESY nmr data along with comparisons to 3. The absolute stereochemistry at the three chir al sites of 5 was assigned by preparing acyclic compounds 6-9, and bot h 8 and 9 were investigated using the modified Mosher's method. This r epresents the first absolute stereochemistry determination for a spong e-derived polyketide peroxide. The characterization of plakoric acid [ 12] was based on spectral analogies co known polyketides such as plako rtin. Plakortolide E [5] exhibited selective potency against the melan oma and breast tumor cell lines in the in vitro 60-cell line panel of the National Cancer Institute.