Total Synthesis and Determination of the Absolute Configuration of Coscinosulfate. A New Selective Inhibitor of Cdc25 Protein Phosphatase

The first total synthesis of coscinosulfate 1, a metabolite isolated from a sea sponge, starting from (+)-sclareolide 3 is described. The convergent s ynthesis strategy relies on the coupling of sulfone 21 with the bromide 26. The sulfone fragment 21 was obtained by successive asymmetric aldol reacti on with aldehyde 2 to introduce the stereocenters at C-12 and C-13, followe d by one-carbon homologation via Horner-Wadsworth-Emmons olefination. The s elective sulfatation at C-12 was accomplished through the quinone intermedi ate 31 obtained by selective oxidation of hydroquinone 30; this, when follo wed by reduction, furnished the desired coscinosulfate 1. X-ray analysis of the intermediate aldehyde IS confirmed the proposed stucture.