Discovery and Total Synthesis of a New Estrogen Receptor Heterodimerizing Actinopolymorphol A from <i>Actinopolymorpha rutilus</i>

Estrogen receptor ERα and ERβ heterodimerization has been implicated in cancer chemoprevention. The discovery, structural elucidation, and total synthesis of a new natural product, actinopolymorphol A (<b>1</b>), from <i>Actinopolymorpha rutilus</i> (YIM45725) that preferentially induces ERα/β heterodimerization is reported. Total synthesis of <b>1</b> has allowed us to determine its absolute stereochemistry and that of a previously known deacetylated congener, and <b>1</b> represents the first member of a new class of natural products not previously recognized to modulate ER function.