Abstract
Pladienolide, a naturally occurring antitumor molecule discovered by a cell–based reporter gene expression assay, shows prominent antitumor activities in diverse in vitro and in vivo systems based on a unique mechanism of action. The first total synthesis of pladienolides B and D was accomplished to confirm absolute configuration of ten asymmetric centers of pladienolides. Despite the unique mechanism of action, the target protein of pladienolide remained unclear. Binding protein identification by using several types of pladienolide’s derivatives as ‘chemical probes’ demonstrated that splicing factor SF3b is a pharmacologically relevant protein target of pladienolide.
