A multi-gram-scale stereoselective synthesis of Z-endoxifen

Bioorg Med Chem Lett. 2018 May 1;28(8):1352-1356. doi: 10.1016/j.bmcl.2018.03.008. Epub 2018 Mar 13.

Abstract

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.

Keywords: Antiestrogens; Endoxifen; MHJBZVSGOZTKRH-IZHYLOQSSA-N; Nuclear receptors; Stereoselective synthesis; Tamoxifen analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / chemical synthesis*
  • Antineoplastic Agents, Hormonal / chemistry
  • Stereoisomerism
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / chemical synthesis
  • Tamoxifen / chemistry

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen