Isolation, structural elucidation, and stereochemistry of phosphoeleganin, a potent cytotoxic phosphate-containing polyketide isolated from the Mediterranean ascidian Sidnyum elegans

The cytotoxic properties of marine metabolites are of particular interest for the development of new anticancer agents, and there is a continuing interest in identifying such compounds that have novel structural features. These new chemotypes can serve as possible drug development candidates in their own right, or they may provide new structural scaffolds for the synthetic or semisynthetic production of lead compounds. In this field, the chemistry of ascidians has become one of the most interesting branch, highlighted by a broad range of potent bioactive compounds that have been isolated from these organisms. Infact, a significant number of ascidian-derived compounds have entered into preclinical and clinical trials as antitumor agents. In the course of our search for cytotoxic compounds from Mediterranean ascidians , we have investigated the ascidian Sidnyum elegans (Giard, 1872) collected in Sardinia; this study resulted in the isolation of a potent cytotoxic phosphate-containing linear polyketide, named phosphoeleganin. The structure of the novel metabolite, including stereochemistry details, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Phosphoeleganin showed significant cytotoxicity against different cell lines in vitro; interestingly, one of its derivatization products was shown to be more active than the original metabolite.