The Discovery of Potent Antitumor Agent C11-Deoxypsymberin/irciniastatin A: Total Synthesis and Biology of Advanced Psymberin Analogs

Structure-activity relationship (SAR) studies by modification of the unsaturated side chain of potent anticancer marine natural product psymberin/irciniastatin A (1) suggest that substitution at C4 and C5 is important for the cytotoxicity of psymberin, but the terminal double bond is not essential for activity. An aryl group is a good replacement for the olefin. The total synthesis of structurally simplified C11-deoxypsymberin (29) was completed, and its activity is consistently more potent than the natural product which provides a unique opportunity for further SAR studies in the psymberin and pederin family. Preliminary mechanism studies suggest the mode of action of psymberin is through cell apoptosis.