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Synthesis 2009(17): 2963-2969  
DOI: 10.1055/s-0029-1216909
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies of the Asymmetric Total Synthesis of Clavilactone D by the ‘Lariat’ Cyclization Strategy

Takehiko Yoshimitsu*, Shoji Nojima, Masashi Hashimoto, Koji Tsukamoto, Tetsuaki Tanaka*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Fax: +81(6)68798214; e-Mail: yoshimit@phs.osaka-u.ac.jp;
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Publication History

Received 30 May 2009
Publication Date:
23 July 2009 (online)

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Abstract

A route to the core structure of clavilactone D, a new member of the tyrosine kinase inhibitors, is reported. The route employs sequential cyclization initiated by iodo etherification followed by Friedel-Crafts cyclization to furnish a polycyclic lactone fused with an aromatic ring, which is readily transformed into the proposed clavilactone scaffold.

Key words

total synthesis - natural products - cyclizations - asymmetric synthesis - alkylations

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2

The absolute stereochemistry of natural clavilactone D shown in this paper is provided on the basis of the revised structure of clavilactone B (see ref. 4), a closely related congener of clavilactone D.

11

The racemic crystal was more suitable for X-ray crystallographic analysis than the chiral one.

12

CCDC 733571 contains the supplementary X-ray crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.