Discovery and total synthesis of a new estrogen receptor heterodimerizing actinopolymorphol A from Actinopolymorpha rutilus

Abstract

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