Discovery and total synthesis of a new estrogen receptor heterodimerizing actinopolymorphol A from Actinopolymorpha rutilus.
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.
Huang
Sheng-Xiong
SX
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Powell
Emily
E
Rajski
Scott R
SR
Zhao
Li-Xing
LX
Jiang
Cheng-Lin
CL
Duan
Yanwen
Y
Xu
Wei
W
Shen
Ben
B
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000192:Actinomycetales / Q000737:chemistry*; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000085:Acetates; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; C552534:actinopolymorphol A