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Synthesis 2009(17): 2927-2934  
DOI: 10.1055/s-0029-1216923
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Second-Generation, Biomimetic Total Synthesis of Chaetominine

Alexis Coste, Ganesan Karthikeyan, François Couty, Gwilherm Evano*
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin en Yvelines, 45 Avenue des Etats-Unis,78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: evano@chimie.uvsq.fr;
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Publication History

Received 1 July 2009
Publication Date:
30 July 2009 (online)

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Abstract

A straightforward total synthesis of the potent anticancer agent (-)-chaetominine is reported. Central to this synthesis was a biomimetic oxidative cyclization of a tryptophanyl-alanine dipeptide, which provided a fully elaborated 1,2,3,4-tetrahydropyrido[2,3-b]indole. Reduction of this intermediate followed by spontaneous cyclization and installation of the side chain provided synthetic chaetominine in a nine-step sequence in 14% overall yield starting from commercially available, inexpensive starting materials.

Key words

alkaloids - total synthesis - oxidative cyclization - anticancer agents - peptides

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Electrostatic repulsion between the phthalimide protecting group and the incoming electrophile might also account for the high stereoselectivity observed

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ArgusLab 4.0; Mark A. Thompson, Planaria Software LLC: Seattle; see: http://www.ArgusLab.com.