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Synthesis of (−)-Dactylolide and 13-Desmethylene-(−)-dactylolide and Their Effects on Tubulin

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journal contribution
posted on 21.05.2010, 00:00 by Didier Zurwerra, Jürg Gertsch, Karl-Heinz Altmann
An efficient new synthesis has been elaborated for non-natural (−)-dactylolide ((−)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with β-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (−)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC50 values in the sub-micromolar range and induce the polymerization of tubulin in vitro.

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