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

Lech-Gustav Milroy; Bartjan Koning; Daphne S V Scheppingen; Nynke G L Jager; Jos H Beijnen; Jan Koek; Luc Brunsveld

doi:10.1016/j.bmcl.2018.03.008

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

Lech-Gustav Milroy, Bartjan Koning, Daphne S V Scheppingen, Nynke G L Jager, Jos H Beijnen, Jan Koek, Luc Brunsveld

Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands. Electronic address: [email protected].
Syncom B.V., Kadijk 3, 9747 AT Groningen, The Netherlands.
Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek and MC Slotervaart, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1352-1356
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2018.03.008
Publication status	Published - 1 May 2018

Keywords

Antiestrogens
Tamoxifen analogs
Endoxifen
Nuclear receptors
Stereoselective synthesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2018.03.008

1-s2.0-S0960894X18301835-mainFinal published version, 850 KBLicence: CC BY-NC-ND

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title = "A multi-gram-scale stereoselective synthesis of Z-endoxifen",

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, Tamoxifen analogs, Endoxifen, Nuclear receptors, Stereoselective synthesis",

author = "Lech-Gustav Milroy and Bartjan Koning and Scheppingen, \{Daphne S V\} and Jager, \{Nynke G L\} and Beijnen, \{Jos H\} and Jan Koek and Luc Brunsveld",

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AU - Milroy, Lech-Gustav

AU - Koning, Bartjan

AU - Scheppingen, Daphne S V

AU - Jager, Nynke G L

AU - Beijnen, Jos H

AU - Koek, Jan

AU - Brunsveld, Luc

PY - 2018/5/1

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KW - Antiestrogens

KW - Tamoxifen analogs

KW - Endoxifen

KW - Nuclear receptors

KW - Stereoselective synthesis

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JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

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ER -

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

Abstract

Keywords

UN SDGs

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