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

doi:10.1016/j.bmcl.2018.03.008

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 language	English
Pages (from-to)	1352-1356
Number of pages	5
Journal	Bioorganic and 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
Endoxifen
MHJBZVSGOZTKRH-IZHYLOQSSA-N
Nuclear receptors
Stereoselective synthesis
Tamoxifen analogs
Tamoxifen/analogs & derivatives
Stereoisomerism
Antineoplastic Agents, Hormonal/chemical 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

Cite this

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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.",

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AU - Milroy, L.G.

AU - Koning, B.

AU - Scheppingen, D.S.V.

AU - Jager, N.G.L.

AU - Beijnen, J.H.

AU - Koek, J.

AU - Brunsveld, L.

PY - 2018/5/1

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N2 - 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.

AB - 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.

KW - Antiestrogens

KW - Endoxifen

KW - MHJBZVSGOZTKRH-IZHYLOQSSA-N

KW - Nuclear receptors

KW - Stereoselective synthesis

KW - Tamoxifen analogs

KW - Tamoxifen/analogs & derivatives

KW - Stereoisomerism

KW - Antineoplastic Agents, Hormonal/chemical synthesis

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JO - Bioorganic and 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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