An improved route to (+)-tedanolide and analysis of its subtle effects controlling conformation and biological behaviour.

The improved synthesis of the antitumor compound (+)-tedanolide is described through an aldol coupling of bis-ketone 7. This modification shortens the synthetic steps in the endgame and provides rapid access to this biologically important natural product. Additionally, it serves as a probe in order to unravel the conformational effects that impede or enable its successful synthesis. Having this way access to des-epoxy-tedanolide, its biological characterization surprisingly unravelled the mode of action to resemble candidaspongiolide rather than deoxytedanolide.