New Cytotoxic 1,2,4-Thiadiazole Alkaloids from the Ascidian Polycarpa aurata

Two new alkaloids, polycarpathiamines A and B (1 and 2), were isolated from the ascidian Polycarpa aurata. Their structures were unambiguously determined by 1D, 2D NMR, and HRESIMS measurements and further confirmed by comparison with a closely related analogue, 3-dimethylamino-5-benzoyl-1,2,4-thiadiazole (4), that was prepared by chemical synthesis. Compounds 1 and 2 both feature an uncommon 1,2,4-thiadiazole ring whose biosynthetic origin is proposed. Compound 1 showed significant cytotoxic activity against L5178Y murine lymphoma cells (IC50 0.41 μM).