Synthesis and biological evaluation of new jasplakinolide (jaspamide) analogs

Eight new jasplakinolide derivatives were synthesized and evaluated for antitumor activity by measuring their ability to interfere with the actin cytoskeleton. Simplified derivative 4 is essentially as active as natural jasplakinolide. Synthesis and biological evaluation of jasplakinolide analogs are described. The synthesis of analogs utilized a diastereoselective syn-aldol reaction and an orthoester Claisen rearrangement as key steps. All synthetic analogs were evaluated for their ability to disrupt the actin cytoskeleton. Compounds 2, 3, and 4 essentially displayed similar activity to jasplakinolide.