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Highlights► We analyzed the effects of cyclin D1 on the migration of cancer cell lines. ► The Wnt pathway promotes cellular migration via its target gene cyclin D1. ► Cyclin D1 rearranges the actin cytoskeleton and destabilizes adherens junctions.

The spiro[5.5]ketal moiety forms the underlying structural skeleton of numerous biologically active natural products. Since simplified but characteristic spiroketals derived from the parent natural products retain biological activity, the spiro[5.5]ketal unit can be regarded as a biologically prevalidated framework for the development of natural product‐derived compound collections. We report an enantioselective synthesis of spiro[5.5]ketals on solid support. The reaction sequence employs asymmetric boron enolate aldol reactions with the enolate bound to the polymer or in solution as the key enantiodifferentiating step. It proceeds in up to 12 steps on solid support, makes the desired spiroketals available in high overall yields and with high stereoselectivities and is amenable to structural variation of the products. The small spiroketal collection synthesized contains phosphatase inhibitors and compounds that modulate the formation of the tubulin cytoskeleton in human cancer cells without directly targeting microtubules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Ras‐tplatz: Die Anwendung einer effizienten Strategie für Phänotyp‐basiertes Screening von Bibliotheken auf eine Serie von Sulindac‐Derivaten (siehe Schema) führte zur Entdeckung von Inhibitoren des Ras‐Signalwegs. Die Ergebnisse unterstreichen den Vorteil der Verwendung von biologisch vorvalidierten Verbindungsklassen in der chemisch‐biologischen Forschung.

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The cover picture shows the stereoselective solid‐phase synthesis of highly substituted spiroketal molecules. Asymmetric aldol reactions on a solid phase are the key steps involved in this synthetic route. Both resin‐bound β‐hydroxy aldehydes and boron enolates were employed for syn‐ and anti‐aldol reactions, respectively. Out of this small collection of spiroacetals, some molecules showed activities against tubulin polymerization. The effect of two different spiroketals at a concentration of 5 μm on the tubulin cytoskeleton is shown in the picture (top right and bottom left). Furthermore, some spiroketals were found to be phosphatase inhibitors. Details are discussed in the article by H. Waldmann et al. on p. 4773 ff.