Synthesis and Biological Activity of trans-2,3-Dihydroraloxifene.

The synthesis and biological evaluation of trans-2,3-dihydroraloxifene, 2, is described. The synthesis proceeds in 8 steps in 20% overall yield. Relative trans 2,3-stereochemistry is definitively established in ester 6, which is converted to the title compound via derivatization, Grignard addition, and deprotection. Evaluation in vitro shows the compound to be a potent selective estrogen receptor modulator (SERM).