Cyclic Polyketide Peroxides and Acyclic Diol Analogues from the Sponge Plakortis lita

The sponge Plakortis lita from Papua New Guinea is a source of three cyclic peroxides-ethyl plakortide Z (3), ethyl didehydroplakortide Z (4), and methyl didehydroplakortide Z (5)-and three acyclic diol analogues-ethyl seco-plakortide Z (6), epi-ethyl seco-plakortide Z (7), and ethyl didehydro-seco-plakortide Z (8). The absolute stereochemistry at the three chiral sites of 3 was assigned by preparing 6, which was investigated using the refined Mosher's method. Compounds 4, 5, and 6 were also concluded to have the same absolute stereochemistry as 3. The cyclic peroxides were generally cytotoxic, while the acyclic analogues were devoid of activity. Compound 3 was equally active in vitro against solid tumor and L-1210 leukemia cell lines. Alternatively, 4 was observed in vitro to be moderately solid-tumor selective but did not exhibit in vivo activity against solid tumors in mice.