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Synlett 2011(2): 191-194  
DOI: 10.1055/s-0030-1259286
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Studies towards Leiodermatolide: Rapid Stereoselective Syntheses of Key Fragments

Vaidotas Navickas, Christian Rink, Martin E. Maier*
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Fax: +49(7071)295137; e-Mail: martin.e.maier@uni-tuebingen.de;
Further Information

Publication History

Received 3 November 2010
Publication Date:
23 December 2010 (online)

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Abstract

The synthesis of three key fragments of the novel 16-membered macrolide leiodermatolide is described. The stereotetrad-containing building block was prepared via a Marshall-Tamaru reaction on an aldehyde obtained by organocatalysis. For a second building block, a Marshall-Tamaru reaction was used as well. The side-chain fragment containing a hydroxy δ-lactone could be obtained by intramolecular Reformatsky reaction.

Key words

leiodermatolide - macrolide - Marshall-Tamaru reaction - intramolecular Reformatsky reaction - Fráter-Seebach alkylation

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2

The following IC50 values are reported: A549, P399 = 3.3 nM, PANC-1 = 5.0 nM, DLD-1 = 8.3 nM, NCI-ADR-Res = 233 nM.