Total Synthesis of Dinophysistoxin-2 and 2-epi-Dinophysistoxin-2 and Their PPase Inhibition


  • We acknowledge the Ohio State University for financial support, Dr. T. Young and A.-K. Yassine for technical help, the Ohio BioProduct Innovation Consortium for mass spectrometry support, and Prof. J. Stambuli for helpful discussion.


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The first total syntheses of the title compounds highlight novel assemblies of the C1–C14 and C28–C38 domains, including an unexpected diastereoselectivity in the Sharpless asymmetric dihydroxylation of an alkene at C1[DOUBLE BOND]C2. PPase inhibition assays revealed that 2-epi-DTX-2 is at least 1 to 2 orders of magnitude less potent than DTX-2, thus indicating that the configuration at C2 in DTX-2 is crucial for potent inhibition (see picture).