Total Syntheses and Biological Investigations of Tamandarins A and B and Tamandarin A Analogs

Tamandarins A (<b>1</b>) and B (<b>2</b>), two natural products similar in structure to didemnin B (<b>3</b>), were recently isolated from a Brazilian marine ascidian of the family Didemnidae. The cytotoxicity of <b>1</b> was reported to be somewhat more potent in vitro than that of <b>3</b> against various human cancer cell lines. The present account describes the first total syntheses of <b>1 </b>and<b> 2</b>, and the syntheses of tamandarin A side chain analogues. The cytotoxicity data for these compounds show that the side chain modifications exhibit a parallel effect for both didemnins and tamandarins. This observation supports tamandarins' role as didemnins' mimic.