Z-Endoxifen is widely regarded as the most active metabolite of tamoxifen, and has recently demonstrated a 26.3% clinical benefit in a phase I clinical trial to treat metastatic breast cancer after the failure of standard endocrine therapy. Future pharmacological and pre-clinical studies of Z-endoxifen would benefit from reliable and efficient synthetic access to the drug. Here, we describe a short and efficient, stereoselective synthesis of Z-endoxifen capable of delivering multi-gram (37 g) quantities of the drug in >97% purity with a Z/E ratio >99% after trituration.

中文翻译：

---

Z- endoxifen的多克级立体选择性合成

Z- Endoxifen被广泛认为是他莫昔芬最活跃的代谢产物，最近在标准内分泌疗法失败后的转移性乳腺癌的I期临床试验中显示出26.3％的临床获益。Z-endoxifen的未来药理和临床前研究将受益于可靠有效的药物合成途径。在这里，我们描述了一种短而有效的，立体选择性的Z-内多昔芬合成方法，该方法能够在研磨后以> 97％的纯度提供多克（37 g）量的药物，Z / E比率> 99％。