Synthesis of amide analogs of arenastatin A

In order to probe the metabolism of arenastatin A, a potent cytotoxic depsi peptide from the marine sponge Dysidea arenaria, we synthesized three analo gs in which the ester linkages were replaced by amide bonds. Triamide analo g-II and tetraamide analog, both of which contained a 15,20-amide linkage, showed stability in serum. However, arenastatin A and triamide analog-I, wh ich both contained a 15,20-ester moiety, were readily metabolized in serum. Among the three amide analogs, only triamide analog-II exhibited potent cy totoxic activity against KB cells. (C) 2000 Elsevier Science Ltd. All right s reserved.