Abstract
Tamoxifen (TAM) comprises a triphenylethylene derivative with pronounced activity as Selective Estrogen Receptor Modulator (SERM) that acts on the Estrogen Receptor (ER)-positive breast cancer cells preventing the tumorigenesis in high risk women. TAM constitutes the most prescribed chemotherapeutic drug for the treatment of breast cancer, acting through its in vivo metabolites (Z)- 4-hydroxytamoxifen (Z-4-HTAM) and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). Literature search has indicated that the efficient construction of TAM backbone is achieved through three major routes. One concerns the formation of the appropriately phenylsubstituted double bond of TAM, a second includes the reductive coupling of two aromatic ketones and the third refers to the coupling of olefins with metallated aromatics in the presence of transition metal catalysts. A deconstruction of these pathways and a comprehensive picture of the synthetic strategies towards the efficient approach of TAM are presented in this review. Furthermore, novel synthetic routes that differentiate or act complementary to these general routes are also considered. Issues such as the reactions efficiency and stereoselectivity have also been addressed.
Keywords: Tamoxifen, antiestrogen, breast cancer, SERM, carbometallation, organometallic nucleophiles
Current Organic Chemistry
Title: Tamoxifen: A Synthetic Overview
Volume: 16 Issue: 3
Author(s): Konstantinos M. Kasiotis and Serkos A. Haroutounian
Affiliation:
Keywords: Tamoxifen, antiestrogen, breast cancer, SERM, carbometallation, organometallic nucleophiles
Abstract: Tamoxifen (TAM) comprises a triphenylethylene derivative with pronounced activity as Selective Estrogen Receptor Modulator (SERM) that acts on the Estrogen Receptor (ER)-positive breast cancer cells preventing the tumorigenesis in high risk women. TAM constitutes the most prescribed chemotherapeutic drug for the treatment of breast cancer, acting through its in vivo metabolites (Z)- 4-hydroxytamoxifen (Z-4-HTAM) and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). Literature search has indicated that the efficient construction of TAM backbone is achieved through three major routes. One concerns the formation of the appropriately phenylsubstituted double bond of TAM, a second includes the reductive coupling of two aromatic ketones and the third refers to the coupling of olefins with metallated aromatics in the presence of transition metal catalysts. A deconstruction of these pathways and a comprehensive picture of the synthetic strategies towards the efficient approach of TAM are presented in this review. Furthermore, novel synthetic routes that differentiate or act complementary to these general routes are also considered. Issues such as the reactions efficiency and stereoselectivity have also been addressed.
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Cite this article as:
M. Kasiotis Konstantinos and A. Haroutounian Serkos, Tamoxifen: A Synthetic Overview, Current Organic Chemistry 2012; 16 (3) . https://dx.doi.org/10.2174/138527212799499886
DOI https://dx.doi.org/10.2174/138527212799499886 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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