Studies on Total Syntheses of Cytotoxic Cyclic Peptides of Marine Origin

Cyclic peptides from marine organisms constitute a growing class of naturally occurring cytotoxic substances. A general synthetic method for thiazole amino acids, common components of these cyclic peptides 1-7, has been developed and total syntheses of 1-7 have been achieved. In the process, dolastatin 3 with the proposed structure has been disclosed to differ from the natural material and the real structure 2 has been confirmed by its total synthesis. Patellamides with the proposed structures has been revised to be 6 by their total syntheses. Absolute configuration of ascidiacyclamide has been determined to be 4 and the structure of ulithiacyclamide has been confirmed. Ulicyclamide has been efficiently prepared in combination with solid and liquid phase syntheses. Didemnins A and B, cyclic depsipeptides with potent antitumor activity, have been prepared by condensation of the key eastern and western fragments.