Synthesis of psymberin analogues: probing a functional correlation with the pederin/mycalamide family of natural products

In this letter we describe an efficient synthesis of "psympederin", a hybrid between the novel antitumor natural product psymberin and the blister beetle toxin pederin. Evaluation of antiproliferative activity reveals that the dihydroisocoumarin fragment is important for psymberin toxicity and the cyclic pederate fragment is important for pederin/mycalamide toxicity. On the basis of preliminary results described herein, we speculate that, despite their structural resemblance, psymberin and pederin/mycalamide induce toxicity through different mechanisms. [reaction: see text].