Discovery of New Cytotoxic Aplaminone Derivatives from the Sea Hare Aplysia kurodai and Elucidation of Their Accumulation from Local Sea Algae through the Food Chain

The shell-less herbivorous marine mollusk (sea hare) Aplysia kurodai is known to contain a variety of bioactive substances. While these compounds have been thought to originate from sea algae or their associated microbes, most of their origin and acquisition pathways are still unclear. Six new cytotoxic aplaminone derivatives, bromodopamine-terpenoid hybrid molecules, were isolated from A. kurodai. Among them, isoaplaminone had a reverse prenyl group at the C15 aliphatic chain, which is a rare structural feature from the viewpoint of terpenoid biosynthesis. Investigation for chemical components in A. kurodai and the sea algae collected at several different locations revealed that two major aplaminones were contained in the Laurencia complex species at specific sites. Our chemical and ecological studies provide new insights into the origin of marine alkaloid toxins and their dynamism through the food chain.