blocks_imageAvrainvillamide and its dimerization product stephacidin B are antiproliferative agents isolated from fungi. We have developed a highly convergent synthetic route to avrainvillamides and demonstrated that avrainvillamide and stephacidin B readily equilibrate under physiological conditions. Both stephacidin B and avrainvillamide exhibit submicromolar antiproliferative effects in cultured human cancer cells. We have prepared an extensive library of avrainvillamide analogs and determined important structure-activity relationships. In affinity-isolation experiments using a biotin-conjugated avrainvillamide probe, we determined that the nucleolar phosphoprotein nucleophosmin (NPM) is a target of avrainvillamide.