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Synthesis 2011(14): 2321-2333  
DOI: 10.1055/s-0030-1260073
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Synthesis of Fused-Tetracyclic Scaffolds Employing a Lewis Acid Promoted Domino Reaction of Naphthoquinones

Yassine Bendiabdellah, Isabel Villanueva-Margalef, Antonio Misale, Kazi S. Nahar, Mohammad R. Haque, David E. Thurston, Giovanna Zinzalla*
Cancer Research UK Protein-Protein Interactions Drug Discovery Research Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK
Fax: +44(20)77535964; e-Mail: giovanna.zinzalla@pharmacy.ac.uk;
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Publication History

Received 2 March 2011
Publication Date:
16 June 2011 (online)

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Abstract

The facile synthesis of tetracyclic molecular frameworks employing a Lewis acid promoted domino reaction of naphthoquinones with hydroxy- and amino-functionalized cross-conjugated trienes is reported. The reaction cascade involves a heterocyclization via hemiacetal or imine formation, and an intramolecular Diels­-Alder cycloaddition.

Key words

tetracyclic scaffolds - naphthoquinone - Lewis acid promoted domino reaction - intramolecular Diels-Alder cycloaddition

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The reactions were monitored by LC-MS and TLC on silica gel.

9

The structures and relative stereochemistries were unambiguously assigned by 1D and 2D NMR experiments (including NOESY). Full characterization of the novel skeletons with their NMR data and spectra are included in the Supporting Information.