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

L.G. Milroy, B. Koning, D.S.V. Scheppingen, N.G.L. Jager, J.H. Beijnen, J. Koek, L. Brunsveld

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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.

Original languageEnglish
Pages (from-to)1352-1356
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume28
Issue number8
DOIs
Publication statusPublished - 1 May 2018

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Keywords

  • Antiestrogens
  • Endoxifen
  • MHJBZVSGOZTKRH-IZHYLOQSSA-N
  • Nuclear receptors
  • Stereoselective synthesis
  • Tamoxifen analogs
  • Tamoxifen/analogs & derivatives
  • Stereoisomerism
  • Antineoplastic Agents, Hormonal/chemical synthesis

Cite this

Milroy, L. G., Koning, B., Scheppingen, D. S. V., Jager, N. G. L., Beijnen, J. H., Koek, J., & Brunsveld, L. (2018). A multi-gram-scale stereoselective synthesis of Z-endoxifen. Bioorganic and Medicinal Chemistry Letters, 28(8), 1352-1356. https://doi.org/10.1016/j.bmcl.2018.03.008