Thelepamide: An Unprecedented Ketide-Amino Acid from Thelepus crispus, a Marine Annelid Worm

Thelepamide (1) was characterized during a program to study cytotoxic substances from an unusual source, the tidal zone-derived annelid Thelephus crispus. Its structure contains a tetraketide and a tripeptide subunit and possesses striking atom diversity, consisting of 17 carbons and 8 heteroatoms. The relative configurations at four chiral sites were elucidated via ROESY, J-based configurational analysis, and DFT calculations. It was modestly active against leukemia cells (IC50 = 5 mu g/mL) and inactive against solid tumor cell lines.