New Highly Stereoselective Synthesis of (Z)-4-Hydroxytamoxifen and (Z)-4-Hydroxytoremifene via McMurry Reaction

摘要

(Z)-Tamoxifen (1) is the first antiestrogen to be widely used for the treatment of breast cancer, and this drug is presently being evaluated for preventive therapy for breast cancer in normal women. (Z)-Toremifene (2) has recently been introduced for the treatment of advanced breast cancer. (Z)-4-Hydroxytamoxifen (3), a metabolite of (Z)-tamoxifen (1), is the active antiestrogenic compound. We presume that (Z)-4-hydroxytoremifene (4), a metabolite of (Z)-toremifene (2), has a role similar to that of (Z)-4-hydroxytamoxifen (3). Our interest in these hydroxylated triphenylethylene derivatives is to reach a better understanding of their contribution in the observed (Z)-tamoxifen (1) and (Z)-toremifene (2) biological activities, and the development of resistance to treatment.